| 1. |
|
|
| 2. |
- Bousquet, Jean, et al.
(author)
-
Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
-
In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
-
Journal article (peer-reviewed)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
|
|
| 3. |
- Jones, Benedict C, et al.
(author)
-
To which world regions does the valence-dominance model of social perception apply?
- 2021
-
In: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Journal article (peer-reviewed)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
|
|
| 4. |
- Conti, David, V, et al.
(author)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 5. |
- Adams, Charleen, et al.
(author)
-
Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
- 2019
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:1, s. 208-216
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
|
|
| 6. |
- Bousquet, J. Jean, et al.
(author)
-
Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
-
In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
-
Research review (peer-reviewed)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
|
|
| 7. |
- Forouzanfar, Mohammad H, et al.
(author)
-
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
|
|
| 8. |
- Gonzalez, Arantxa, et al.
(author)
-
Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
- 2022
-
In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 927-943
-
Research review (peer-reviewed)abstract
- Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
|
|
| 9. |
- Law, Philip J., et al.
(author)
-
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
|
|
| 10. |
- Ade, Peter, et al.
(author)
-
The Simons Observatory : science goals and forecasts
- 2019
-
In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
-
Journal article (peer-reviewed)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
|
|
| 11. |
- Aguilera, Anabella, et al.
(author)
-
C-ferroptosis is an iron-dependent form of regulated cell death in cyanobacteria
- 2021
-
In: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 221:2
-
Journal article (peer-reviewed)abstract
- Ferroptosis is an oxidative and iron-dependent form of regulated cell death (RCD) recently described in eukaryotic organisms like animals, plants, and parasites. Here, we report that a similar process takes place in the photosynthetic prokaryote Synechocystis sp. PCC 6803 in response to heat stress. After a heat shock, Synechocystis sp. PCC 6803 cells undergo a cell death pathway that can be suppressed by the canonical ferroptosis inhibitors, CPX, vitamin E, Fer-1, liproxstatin-1, glutathione (GSH), or ascorbic acid (AsA). Moreover, as described for eukaryotic ferroptosis, this pathway is characterized by an early depletion of the antioxidants GSH and AsA, and by lipid peroxidation. These results indicate that all of the hallmarks described for eukaryotic ferroptosis are conserved in photosynthetic prokaryotes and suggest that ferroptosis might be an ancient cell death program.
|
|
| 12. |
- Aimo, Alberto, et al.
(author)
-
Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
- 2022
-
In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 944-958
-
Research review (peer-reviewed)abstract
- In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
|
|
| 13. |
- Bonebrake, Timothy C., et al.
(author)
-
Managing consequences of climate-driven species redistribution requires integration of ecology, conservation and social science
- 2018
-
In: Biological Reviews. - : Wiley-Blackwell Publishing Inc.. - 1464-7931 .- 1469-185X. ; 93:1, s. 284-305
-
Research review (peer-reviewed)abstract
- Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic directions in this nascent research area, emphasising emerging themes in species redistribution biology, the importance of understanding underlying drivers and the need to anticipate novel outcomes of changes in species ranges. We highlight that species redistribution has manifest implications across multiple temporal and spatial scales and from genes to ecosystems. Understanding range shifts from ecological, physiological, genetic and biogeographical perspectives is essential for informing changing paradigms in conservation science and for designing conservation strategies that incorporate changing population connectivity and advance adaptation to climate change. Species redistributions present challenges for human well-being, environmental management and sustainable development. By synthesising recent approaches, theories and tools, our review establishes an interdisciplinary foundation for the development of future research on species redistribution. Specifically, we demonstrate how ecological, conservation and social research on species redistribution can best be achieved by working across disciplinary boundaries to develop and implement solutions to climate change challenges. Future studies should therefore integrate existing and complementary scientific frameworks while incorporating social science and human-centred approaches. Finally, we emphasise that the best science will not be useful unless more scientists engage with managers, policy makers and the public to develop responsible and socially acceptable options for the global challenges arising from species redistributions.
|
|
| 14. |
- Falster, Daniel, et al.
(author)
-
AusTraits, a curated plant trait database for the Australian flora
- 2021
-
In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Journal article (peer-reviewed)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
|
|
| 15. |
- Pecl, Gretta T., et al.
(author)
-
Biodiversity redistribution under climate change : Impacts on ecosystems and human well-being
- 2017
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6332
-
Research review (peer-reviewed)abstract
- Distributions of Earth's species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation's Sustainable Development Goals.
|
|
| 16. |
- Pineda-Moncusí, Marta, et al.
(author)
-
Classification of patients with osteoarthritis through clusters of comorbidities using 633,330 individuals from Spain
- 2023
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332. ; 62:11, s. 3592-3600
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of osteoarthritis (OA) and estimate the 10-year mortality risk for each identified cluster.METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand, or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative from Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥ 1% of the individuals (n = 35) were fitted into two cluster algorithms, K-means and latent class analysis (LCA). Models were assessed using a range of internal and external criteria evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used LCA to identify four clusters: 'Low-morbidity (relatively low number of comorbidities), 'Back/neck pain plus mental health', 'Metabolic syndrome' and 'Multimorbidity' (higher prevalence of all study comorbidities). Compared with the 'Low-morbidity, the 'Multimorbidity' cluster had the highest risk of 10-year mortality (adjusted HR: 2.19 [95%CI: 2.15-2.23]), followed by 'Metabolic syndrome' (adjusted HR: 1.24 [95%CI: 1.22-1.27]]) and 'Back/neck pain plus mental health' (adjusted HR: 1.12 [95%CI: 1.09-1.15]).CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.
|
|
| 17. |
- Wain, Louise V, et al.
(author)
-
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
-
Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
|
|
| 18. |
- Xie, Junqing, et al.
(author)
-
Association of Tramadol vs Codeine Prescription Dispensation with Mortality and Other Adverse Clinical Outcomes
- 2021
-
In: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 326:15, s. 1504-1515
-
Journal article (peer-reviewed)abstract
- Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017. Exposures: New prescription dispensation of tramadol or codeine (no dispensation in the previous year). Main Outcomes and Measures: Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models. Results: Of the 1093064 patients with a tramadol or codeine dispensation during the study period (326921 for tramadol, 762492 for codeine, 3651 for both drugs concomitantly), a total of 368960 patients (184480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders. Conclusions and Relevance: In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding..
|
|
| 19. |
- Xie, Junqing, et al.
(author)
-
Trends of Dispensed Opioids in Catalonia, Spain, 2007–19 : A Population-Based Cohort Study of Over 5 Million Individuals
- 2022
-
In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
-
Journal article (peer-reviewed)abstract
- Objective: To characterize the trend of opioid use (number of users, dispensations and oral morphine milligram equivalents) in Catalonia (Spain). Design, setting, and participants: This population-based cohort study included all individuals aged 18 years or older, registered in the Information System for Research in Primary Care (SIDIAP), which covers >75% of the population in Catalonia, Spain, from 1 January 2007, to 31 December 2019. Main exposure and outcomes: The exposures were all commercialized opioids and their combinations (ATC-codes): codeine, tramadol, oxycodone, tapentadol, fentanyl, morphine, and other opioids (dihydrocodeine, hydromorphone, dextropropoxyphene, buprenorphine, pethidine, pentazocine). The main outcomes were the annual figures per 1,000 individuals of 1) opioid users, 2) dispensations, and 3) oral morphine milligram equivalents (MME). Results were stratified separately by opioid types, age (5-year age groups), sex (male or female), living area (rural or urban), and socioeconomic status (from least, U1, to most deprived, U5). The overall trends were quantified using the percentage change (PC) between 2007 and 2019. Results: Among 4,656,197 and 4,798,114 residents from 2007 to 2019, the number of opioid users, dispensations and morphine milligram equivalents per 1,000 individuals increased 12% (percentage change: 95% confidence interval (CI) 11.9–12.3%), 105% (95% confidence interval 83%–126%) and 339% (95% CI 289%–390%) respectively. Tramadol represented the majority of opioid use in 2019 (61, 59, and 54% of opioid users, dispensations, and total MME, respectively). Individuals aged 80 years or over reported the sharpest increase regarding opioid users (PC: 162%), dispensations (PC: 424%), and MME (PC: 830%). Strong opioids were increasingly prescribed for non-cancer pains over the years. Conclusion: Despite the modest increase of opioid users, opioid dispensations and MME increased substantially, particularly in the older population. In addition, strong opioids were incrementally indicated for non-cancer pains over the years. These findings suggest a transition of opioid prescriptions from intermittent to chronic and weak to strong and call for more rigorous opioid stewardship.
|
|
