| 1. |
- Berry, Joe Scott, et al.
(författare)
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Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome : proteomic and network analysis
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes.Method: We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST.Results: Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6.Conclusions: Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes.
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| 2. |
- Cunningham, Janet L., et al.
(författare)
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Experiences in implementing immunopsychiatry in real life
- 2023
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Ingår i: Journal of Affective Disorders Reports. - : Elsevier. - 2666-9153. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Immunological mechanisms, both alone and in combination, are associated with a broad range of psychiatric disorders encompassing autoimmune, autoinflammatory disorders but also genetic, metabolic, or other immunological disorders. Early treatment improves the outcome for autoimmune disorders, but early diagnosis is more difficult when isolated psychiatric symptoms are manifestations of autoimmunity. Treatment of these cases must encompass integrated models of disease, as both systemic autoimmunity and psychological processes influence mental health. Several challenges need to be overcome to efficiently merge psychiatric and somatic disease paradigms and medical care ranging from language and conceptual barriers to organizational barriers. Since 2015, the Immunopsychiatry team at Uppsala University has developed a collaborative multidisciplinary approach to improve and integrate care for patients with moderate to severe psychiatric disorders. Based on this experience, we have outlined the obstacles to be overcome in taking steps forward to achieve the long-term goal of understanding and early detection and identification of treatable immunological conditions within the psychiatric patient population; the described framework of evaluations and work-flow may serve as a model for other centers.
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| 3. |
- Ramos-Casals, Manuel, et al.
(författare)
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EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.
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| 4. |
- Triliva, Sofia, et al.
(författare)
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Healthcare professionals' perspectives on mental health service provision : a pilot focus group study in six European countries
- 2020
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Ingår i: International Journal of Mental Health Systems. - : BioMed Central (BMC). - 1752-4458. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mental healthcare treatment gap (mhcGAP) in adult populations has been substantiated across Europe. This study formed part of MentALLY, a research project funded by the European Commission, which aimed to gather qualitative empirical evidence to support the provision of European mental healthcare that provides effective treatment to all adults who need it.Methods: Seven focus groups were conducted with 49 health professionals (HPs), including psychologists, psychiatrists, social workers, general practitioners, and psychiatric nurses who worked in health services in Belgium, Cyprus, Greece, the Netherlands, Norway and Sweden. The focus group discussions centered on the barriers and facilitators to providing quality care to people with mild, medium, and severe mental health problems. Analyses included deductively and inductively driven coding procedures. Cross-country consensus was obtained by summarizing findings in the form of a fact sheet which was shared for triangulation by all the MentALLY partners.Results: The results converged into two overarching themes: (1) Minding the treatment gap: the availability and accessibility of Mental Health Services (MHS). The mhcGAP gap identified is composed of different elements that constitute the barriers to care, including bridging divides in care provision, obstacles in facilitating access via referrals and creating a collaborative 'chain of care'. (2) Making therapeutic practice relevant by providing a broad-spectrum of integrated and comprehensive services that value person-centered care comprised of authenticity, flexibility and congruence.Conclusions: The mhcGAP is comprised of the following barriers: a lack of funding, insufficient capacity of human resources, inaccessibility to comprehensive services and a lack of availability of relevant treatments. The facilitators to the provision of MHC include using collaborative models of primary, secondary and prevention-oriented mental healthcare. Teamwork in providing care was considered to be a more effective and efficient use of resources. HPs believe that the use of e-mental health and emerging digital technologies can enhance care provision. Facilitating access to a relevant continuum of community-based care that is responsive coordinated and in line with people's needs throughout their lives is an essential aspect of optimal care provision.
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| 5. |
- Van Beveren, Laura, et al.
(författare)
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A Critical Perspective on Mental Health News in Six European Countries : How Are "Mental Health/Illness" and "Mental Health Literacy" Rhetorically Constructed?
- 2020
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Ingår i: Qualitative Health Research. - : Sage Publications. - 1049-7323 .- 1552-7557. ; 30:9, s. 1362-1378
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we aim to contribute to the field of critical health communication research by examining how notions of mental health and illness are discursively constructed in newspapers and magazines in six European countries and how these constructions relate to specific understandings of mental health literacy. Using the method of cluster-agon analysis, we identified four terminological clusters in our data, in which mental health/illness is conceptualized as "dangerous," "a matter of lifestyle," "a unique story and experience," and "socially situated." We furthermore found that we cannot unambiguously assume that biopsychiatric discourses or discourses aimed at empathy and understanding are either exclusively stigmatizing or exclusively empowering and normalizing. We consequently call for a critical conception of mental health literacy arguing that all mental health news socializes its audience in specific understandings of and attitudes toward mental health (knowledge) and that discourses on mental health/illness can work differently in varying contexts.
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