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1.
  • Andree, Maria, et al. (författare)
  • Knowledge Products from Close-To-Practice Research
  • 2024
  • Ingår i: Round table presentation at the NERA-conference, 6-8 March, Malmö University.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • ‘Close-to-practice research’ has received increased attention across the Nordic countries. Following the British Education Research Association (BERA), the notion of ‘close-to-practice research’ is used to refer to educational research that is based on problems in practice, often involves researchers working in partnership with practitioners in schools and addresses issues of relevance to practitioners. This roundtable focuses on how close-to-practice research can contribute to the knowledge base of the teaching profession by bringing together perspectives from didactics, school improvement and educational policy. More specifically, the interest is directed toward what characterizes the knowledge produced through practice-based research that may have significance for teachers' professional knowledge base and practice. The roundtable conversation builds on a previous analysis of what kinds of knowledge products are generated in didactic close-to-practice research where teachers and researchers work together within the research environment Stockholm Teaching & Learning Studies. As a result of this analysis a typology of knowledge products was proposed including: (i) descriptions of knowing, (ii) teaching design, (iii) didactic examples and (iv) methodological tools. It has been proposed that additional knowledge products may be developed, such as artifacts to be used in teaching (e.g. lesson plans, visual representations). The roundtable will include the following points of discussion: 1) a brief presentation of the typology, 2) challenging and developing the typology of knowledge products proposed by previous research by investigating different cases of close-to-practice research from traditions of action research and practice-developing research within subject-didactics, and 3) discussing how the notion of knowledge products may contribute to advancing the conversation on cumulativity in the field of educational research in general, and in relation to syntheses of close-to-practice research in particular. The participants will be engaged in conversations on the desirability and feasibility of striving towards cumulativity.
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2.
  • Bagger-Jörgensen, Harald, et al. (författare)
  • Oesophageal Lichen Planus Successfully Treated with Budesonide Orodispersible Tablets : A Case Report
  • 2024
  • Ingår i: Case Reports in Gastroenterology. - 1662-0631. ; 18:1, s. 266-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Lichen planus is a relatively common inflammatory condition of the nails, skin, and mucosal surfaces. Oesophageal involvement of lichen planus is thought to be very rare, mainly described in case reports, but is associated with a high risk of oesophageal stenosis as well as squamous cell carcinoma. No evidence-based treatment recommendations exist, with the majority of described treatment regimens involving systemic immunosuppression. Case Report: In this case report, we describe a novel approach in treating oesophageal lichen planus in a patient with budesonide orodispersible tablets, a treatment normally reserved for eosinophilic oesophagitis. The patient achieved complete relief of dysphagia, with a followup oesophagogastroduodenoscopy 2 months after treatment commencement being macroscopically and microscopically free of inflammatory activity. This case report is to our knowledge the first to report this treatment regimen in oesophageal lichen planus. Conclusion: We consider a trial of budesonide orodispersible tablets a reasonable initial management as it’s a local therapy specific to the oesophagus with a more benign side effect profile than systemic immunosuppression, but further studies need to be undertaken to corroborate our findings. Also, based on the severity and malignant potential of oesophageal lichen planus, we suggest that physicians be liberal in ordering oesophagogastroduodenoscopy with biopsy taking as part of the workup of dysphagia in a patient with known lichen planus.
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3.
  • Bohm-Starke, Nina, et al. (författare)
  • Treatment of provoked vulvodynia : A systematic review
  • 2022
  • Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 19:5, s. 789-808
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Treatment recommendations for provoked vulvodynia (PVD) are based on clinical experiences and there is a need for systematically summarizing the controlled trials in this field.Aim: To provide an overview of randomized controlled trials and non-randomized studies of intervention for PVD, and to assess the certainty of the scientific evidence, in order to advance treatment guidelines.Data Sources: The search was conducted in CINAHL (EBSCO), Cochrane Library, Embase (Embase.com), Ovid MEDLINE, PsycINFO (EBSCO) and Scopus. Databases were searched from January 1, 1990 to January 29, 2021.Study Eligibility Criteria: Population: Premenopausal women with PVD. Interventions: Pharmacological, surgical, psychosocial and physiotherapy, either alone or as combined/team-based interventions. Control: No treatment, waiting-list, placebo or other defined treatment. Outcomes: Pain during intercourse, pain upon pressure or touch of the vaginal opening, sexual function/satisfaction, quality of life, psychological distress, adverse events and complications. Study design: Randomized controlled trials and non-randomized studies of interventions with a control group.Study Appraisal and Synthesis Methods: 2 reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias using established tools. The results from each intervention were summarized. Studies were synthesized using a narrative approach, as meta-analyses were not considered appropriate. For each outcome, we assessed the certainty of evidence using grading of recommendations assessment, development, and evaluation (GRADE).Results: Most results of the evaluated studies in this systematic review were found to have very low certainty of evidence, which means that we are unable to draw any conclusions about effects of the interventions. Multimodal physiotherapy compared with lidocaine treatment was the only intervention with some evidential support (low certainty of evidence for significant treatment effects favoring physiotherapy). It was not possible to perform meta-analyses due to a heterogeneity in interventions and comparisons. In addition, there was a heterogeneity in outcome measures, which underlines the need to establish joint core outcome sets.Clinical Implications: Our result underscores the need of stringent trials and defined core outcome sets for PVD.Strength and Limitations: Standard procedures for systematic reviews and the Population Intervention Comparison Outcome model for clinical questions were used. The strict eligibility criteria resulted in limited number of studies which might have resulted in a loss of important information.Conclusion: This systematic review underlines the need for more methodologically stringent trials on interventions for PVD, particularly for multimodal treatments approaches. For future research, there is a demand for joint core outcome sets.
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4.
  • Lexner, Jesper, et al. (författare)
  • The risk for celiac disease after Covid-19 infection
  • 2023
  • Ingår i: BMC Gastroenterology. - 1471-230X. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD. Patients and methods: All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden. Results: During the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75). Conclusions: Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.
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5.
  • Lexner, Jesper, et al. (författare)
  • Well-being and dietary adherence in patients with coeliac disease depending on follow-up
  • 2021
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:4, s. 382-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: It is not clear how follow-up of coeliac disease should be optimally organised. In Malmö, Sweden, patients are followed up by general practitioners (GP), but in Linköping by gastroenterologists (GE). The aim of this study was to investigate if there were any differences in well-being and dietary adherence depending on type of follow-up. Methods: All adult patients with newly diagnosed biopsy-verified coeliac disease in the cities between 2010 and 2014 were offered to participate. Data was retrieved comprising demography, laboratory analyses, questionnaires (Gastrointestinal Symptoms Rating Scale, Short Health Scale, Multidimensional Fatigue Inventory, Psychological General Well-being Index and Short Form 36) and follow-up. Results: In the GP cohort 39/73 patients and in the GE cohort 58/121 agreed to participate (mean age 43 and 44 years, 69 and 60% women, respectively). A follow-up to a dietician was carried out in 31% and 93% of patients, respectively (p <.001). In the GP group 28% had eaten gluten-containing food during the last 4 weeks compared to 9% in the GE group (p =.01). Despite this, no differences could be seen in vitamin or mineral levels. The questionnaires did not indicate any major discrepancies in subjective health. Conclusion: Irrespective of the design of the follow-up physical and mental well-being were comparable. Dietary adherence was not quite as good in the GP group but follow-up in a primary care setting can still be a suitable and equivalent alternative. However, it is crucial that the dietary counselling is structured in a way that ensures dietary adherence.
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6.
  • Ling Lundström, Maria, 1977- (författare)
  • Faecal biomarkers of neutrophil and eosinophil origin in the evaluation of inflammatory bowel disease : Providing insights into the patophysiology
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is characterised by chronic inflammation of the gastrointestinal tract. The gold standard for diagnosing and monitoring IBD is by endoscopy, but biomarkers, like the clinically established faecal calprotectin (FC), can function as non-invasive surrogate markers reflecting disease activity. As FC has some known limitations, it is worthwhile to investigate the performance of alternative faecal markers. Therefore, we aimed to evaluate eosinophil and neutrophil granule proteins as potential faecal biomarkers for different aspects of IBD. An additional aim was to study the association of eosinophils with IBD onset.In Paper I, we explored the role of eosinophils in the pathophysiology of IBD by studying faecal eosinophil markers in a cohort of discordant twin pairs. This study showed that, unlike neutrophils, eosinophils are not active in the pre-clinical state of IBD. Thus, activation of eosinophils is a consequence of inflammation rather than a primary event triggering the onset of disease. In Paper II, the diagnostic association and predictive performance of neutrophil and eosinophil faecal markers were evaluated in a cohort of newly-onset IBD patients. We showed that Myeloperoxidase (MPO) and FC have comparable diagnostic capacities in IBD and that combining FC and MPO could enhance diagnostic accuracy. We also demonstrated that neutrophil markers were predictive of an aggressive disease course in UC. Paper III showed that faecal MPO, human neutrophil lipocalin (HNL) and eosinophil-derived neurotoxin (EDN) – similar to FC – are functioning biomarkers for monitoring clinical remission in IBD patients treated with biologics. The study also demonstrated that faecal EDN and HNL are influenced by corticosteroids, indicating a response mechanism different from that of FC and MPO. In Paper IV we proposed that faecal HNL, reflecting both intestinal neutrophils and epithelial cells, can differentiate patients with gastroenteritis (GE) from new-onset IBD patients.This comprehensive exploration of faecal biomarkers suggests interesting alternatives or adjuncts to FC in the diagnostics, monitoring and prediction of disease course in IBD. By studying these biomarkers, we have also uncovered parts of the IBD pathophysiology and increased the knowledge of the eosinophils in the early state of IBD.
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7.
  • Lundgren, David, 1966- (författare)
  • The significance of low-grade inflammation in the gastrointestinal tract
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundGastrointestinal (GI) symptoms are commonly reported in a normal population. Mostly, the symptoms are of benign cause but occasionally the symptoms can be signs of a more harmful disease. In general, it is difficult to distinguish whether the reported symptoms are caused by a benign (functional) or organic (i.e., inflammatory) disease. To make this distinction, the tools available in clinical practice are medical history, blood and faecal tests, radiology, endoscopy and histological evaluation. Mucosal inflammation usually separates organic from functional disease and, in patients with inflammatory bowel disease (IBD), mucosal inflammation correlates with disease activity. Faecal calprotectin (FC) corresponds well with mucosal inflammation and is in clinical practice often used as the first line non-invasive test for gut inflammation. Although the sensitivity of the FC test to detect gut inflammation is good, there are uncertainties in how to interpret a modestly elevated FC level (i.e., in the span of 50-200µg/g) and in patients with IBD, there is a disagreement into which degree of inflammatory remission it is sufficient to reach.AimThe overall aim of this thesis was to study factors associated with low-grade inflammation based on biochemical markers, and to study the clinical significance of low-grade inflammation in patients with IBD and other patients with elevated FC levels. Is low-grade inflammation associated with reported gastrointestinal symptoms in patients with IBD and could low-grade inflammation be detected in the pre-clinical phase of IBD? How should an elevated FC level in patients with a normal colonoscopy be interpreted and could it be a risk factor for gastrointestinal disease or associated with other factors? Could low-grade inflammation cause IBS-like symptoms in patients with IBD?Methods and resultsThree of the manuscripts on which this thesis is based are from the Faecal and Endoscopic Colorectal Study in Umeå Sweden (FECSU) which consists of 1263 patients that underwent colonoscopy during the period of May 2007 to February 2013. The patients that accepted to participate in the FECSU study performed a FC test the day before the bowel preparation for the colonoscopy and simultaneously filled in questionnaires of gastrointestinal symptoms (GSRS), symptoms of anxiety and depression (HADS) and current medications. A thorough medical chart review that focused on endoscopic evaluations, histological judgements and medical history was performed. The included patients with IBD (n=157) in the FECSU study were analysed separately. Patients with ulcerative colitis (UC) in endoscopic remission reported lower total scores on GSRS-irritable bowel syndrome (GSRS-IBS) than controls (6 vs 10.5; p=0.062). However there was a moderate, yet significant association between GSRS-diarrhoea score and FC levels in the span £ 200 µg/g (rho 0.38;p=0.004) in patients with UC. To investigate pre-clinical biomarkers of IBD we identified 96 patients with IBD in the “Västerbotten Intervention Program (VIP)” and the “Mammography screening project” (MA). In the pre-clinical study in patients with IBD we found that patients who later developed UC had lower plasma albumin levels and patients who later developed Crohn’s disease (CD) had higher levels of CRP in plasma, reflecting signs of a low-grade systemic inflammation years before diagnosis. Plasma calprotectin levels were not elevated before IBD-diagnosis. In the FECSU study, all non-IBD patients with a normal colonoscopy were studied for factors associated with an elevated FC level. Patients with a FC > 50 µg/g more often used Proton-pump inhibitors (PPI) (multivariate OR: 3.843; CI: 2.338-6.316), Non-steroidal anti-ivinflammatory drugs (NSAID) (multivariate OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (ASA) (multivariate OR: 2.934; CI: 1.085-3.448). One third of the patients with a normal colonoscopy had elevated FC levels (> 50 µg/g) and these patients were observed three years after the colonoscopy. There was no increased risk for developing gastrointestinal disease in the patients with an increased baseline FC level and a normal colonoscopy during the observation period.ConclusionPatients with longstanding UC in remission did not experience more IBS-like symptoms than controls. In patients with UC in remission, the FC levels in the lower span were moderately associated with symptoms of diarrhoea. Patients with IBD had elevated inflammatory biochemical markers in blood in the pre-clinical phase. P- CRP and P-albumin were more sensitive to detect a low grade systemic inflammation than P-calprotectin in the pre-clinical phase of IBD. More than one-third of the patients with a normal colonoscopy had a slightly elevated FC. In patients with a normal colonoscopy, the use of PPI, NSAID and ASA was associated with an increased FC level. No significant gastrointestinal disease developed in the patients with an increased FC level together with a normal colonoscopy during the three-year period following colonoscopy. 
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8.
  • Lushnikova, Alexandra, et al. (författare)
  • Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
  • 2021
  • Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:Suppl.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disorder. MC patients have a lower risk of developing colorectal cancer (CRC) than ulcerative colitis (UC) patients. We hypothesize that the immune response in MC is geared more towards immune surveillance of tumor cells than that of UC, which instead contributes to inflammation-associated CRC.Methods: Using Luminex, protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysates from colon biopsies (controls, n = 9; diarrhea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) were analyzed. Soluble checkpoints were analyzed in serum (23 controls, 17 LC, 36 CC and 2 UC).Results: In patients with active LC and CC, CD137, IDO, and CD80 levels were increased compared with one or both control groups. CD152 and PD-1 levels were increased in patients with active CC compared with both control groups. In patients with active UC, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups, IDO levels were increased compared with controls, and CD80 levels were raised compared with diarrhea controls.In sera, CD27, IDO, CD80, PD-1, and PD-L2 levels were decreased in LC patients compared to controls.Conclusions: Increased levels of immune checkpoint molecules in colon biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. Lowered concentrations of soluble immune checkpoint molecules in sera from patients with LC indicate a different level of homeostatic balance systemically in LC patients versus controls.
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9.
  • Lushnikova, Alexandra, et al. (författare)
  • Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
  • 2021
  • Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media S.A.. - 2296-858X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.
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10.
  • Munkvold, Bodil Karoline Ravn, et al. (författare)
  • Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
  • 2021
  • Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
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