| 1. |
- Bassford, Chris, et al.
(författare)
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Developing an intervention around referral and admissions to intensive care : a mixed-methods study
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Background: Intensive care treatment can be life-saving, but it is invasive and distressing for patients receiving it and it is not always successful. Deciding whether or not a patient will benefit from intensive care is a difficult clinical and ethical challenge.Objectives: To explore the decision-making process for referral and admission to the intensive care unit and to develop and test an intervention to improve it.Methods: A mixed-methods study comprising (1) two systematic reviews investigating the factors associated with decisions to admit patients to the intensive care unit and the experiences of clinicians, patients and families; (2) observation of decisions and interviews with intensive care unit doctors, referring doctors, and patients and families in six NHS trusts in the Midlands, UK; (3) a choice experiment survey distributed to UKintensive care unit consultants and critical care outreach nurses, eliciting their preferences for factors used in decision-making for intensive care unit admission; (4) development of a decision-support intervention informed by the previous work streams, including an ethical framework for decision-making and supporting referral and decision-support forms and patient and family information leaflets. Implementation feasibility was tested in three NHS trusts; (5) development and testing of a tool to evaluate the ethical quality of decision-making related to intensive care unit admission, based on the assessment of patient records The tool was tested for inter-rater and intersite reliability in 120 patient records.Results: Influences on decision-making identified in the systematic review and ethnographic study included age, presence of chronic illness, functional status, presence of a do not attempt cardiopulmonary resuscitation order, referring specialty, referrer seniority and intensive care unit bed availability. Intensive care unit doctors used a gestalt assessment of the patient when making decisions. The choice experiment showed that age was the most important factor in consultants’ and critical care outreach nurses’ preferences for admission. The ethnographic study illuminated the complexity of the decision-making process, and the importanceof interprofessional relationships and good communication between teams and with patients and families. Doctors found it difficult to articulate and balance the benefits and burdens of intensive care unit treatment for a patient. There was low uptake of the decision-support intervention, although doctors who used it noted that it improved articulation of reasons for decisions and communication with patients.Limitations: Limitations existed in each of the component studies; for example, we had difficulty recruiting patients and families in our qualitative work. However, the project benefited from a mixed-method approachthat mitigated the potential limitations of the component studies. Conclusions: Decision-making surrounding referral and admission to the intensive care unit is complex. This study has provided evidence and resources to help clinicians and organisations aiming to improve thedecision-making for and, ultimately, the care of critically ill patients.Future work: Further research is needed into decision-making practices, particularly in how best to engage with patients and families during the decision process. The development and evaluation of trainingfor clinicians involved in these decisions should be a priority for future work.
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| 2. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 3. |
- Kommula, S. M., et al.
(författare)
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Effect of Long-Range Transported Fire Aerosols on Cloud Condensation Nuclei Concentrations and Cloud Properties at High Latitudes
- 2024
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 51:6
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Tidskriftsartikel (refereegranskat)abstract
- Active vegetation fires in south-eastern (SE) Europe resulted in a notable increase in the number concentration of aerosols and cloud condensation nuclei (CCN) particles at two high latitude locations—the SMEAR IV station in Kuopio, Finland, and the Zeppelin Observatory in Svalbard, high Arctic. During the fire episode aerosol hygroscopicity κ slightly increased at SMEAR IV and at the Zeppelin Observatory κ decreased. Despite increased κ in high CCN conditions at SMEAR IV, the aerosol activation diameter increased due to the decreased supersaturation with an increase in aerosol loading. In addition, at SMEAR IV during the fire episode, in situ measured cloud droplet number concentration (CDNC) increased by a factor of ∼7 as compared to non-fire periods which was in good agreement with the satellite observations (MODIS, Terra). Results from this study show the importance of SE European fires for cloud properties and radiative forcing in high latitudes.
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| 4. |
- Lyons, Paul A, et al.
(författare)
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Genetically Distinct Subsets within ANCA-Associated Vasculitis
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:3, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND less thanbrgreater than less thanbrgreater thanAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegeners granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanA genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanWe found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanThis study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)
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| 5. |
- Strickson, Sam, et al.
(författare)
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Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex
- 2023
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Ingår i: European Respiratory Journal. - 0903-1936. ; 62:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. Methods In vitro epithelial damage assays and three-dimensional, air–liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. Results We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. Conclusions Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and mucoobstructive features in COPD.
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