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  • 3051.
    Kanina, Aleksandra
    et al.
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Orebro Univ, Sch Med Sci, Orebro, Sweden..
    Sjölander, Arvid
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Butwicka, Agnieszka
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland; Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
    Taylor, Mark
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Martini, Miriam
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundberg, Frida
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian
    Department of Psychological and Brain Sciences, Indiana University, Bloomington Indiana, USA.
    Rosenqvist, Mina
    Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Association Between Cumulative Psychosocial Adversity in the Family and Neurodevelopmental Disorders; a Family-Based Cohort Study2022In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 52, no 6, p. 368-369Article in journal (Other academic)
    Abstract [en]

    Cumulative exposure to psychosocial adversity (PSA) at an early age is a risk factor for developing neuro developmental disorders(NDDs) such as attention-deficit hyperactivity disorder (ADHD) and autism. However, it is not clear if this statistical association reflects a true causal effect. We aimed to assess the degree to which cumulative PSA increases the risk for ADHD and autism while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born from 1990 to 2009 in Sweden who were followed from the age of 3. We created a cumulative index based on 7 PSA factors: large family size, parental bereavement, divorce, low income and education, crime conviction, psychiatric history. We used Cox regression to estimate hazard ratios (HRs) for cumulative PSA and ADHD/autism with 95% confidence intervals (CI) in the general population and among groups of relatives (siblings, half-siblings, and cousins) to address familial confounding. We observed a dose–response relationship between cumulative PSA and ADHD in the general population (adjusted HRs with 95% CI ranged from 1.55 [one adversity: 1.52–1.58] to 2.61 [C 4 adversities: 1.95–3.49]). No clear dose–response relation was seen for autism (adjusted HRs ranged from 1.06 [0.60–1.87] to 1.34 [1.30–1.38]). HRs of ADHD and autism decreased with increasing levels of kinship in the analyses of groups of relatives. These results suggest that familial confounding is an important factor to consider for the associations between cumulative PSA and ADHD/autism which hasn't been done in previous studies.

  • 3052.
    Kankainen, Matti
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Gopalacharyulu, Peddinti
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Holm, Liisa
    Institute of Biotechnology, Department of Biological Sciences, University of Helsinki, Helsinki, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    MPEA--metabolite pathway enrichment analysis2011In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 27, no 13, p. 1878-1879Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: We present metabolite pathway enrichment analysis (MPEA) for the visualization and biological interpretation of metabolite data at the system level. Our tool follows the concept of gene set enrichment analysis (GSEA) and tests whether metabolites involved in some predefined pathway occur towards the top (or bottom) of a ranked query compound list. In particular, MPEA is designed to handle many-to-many relationships that may occur between the query compounds and metabolite annotations. For a demonstration, we analysed metabolite profiles of 14 twin pairs with differing body weights. MPEA found significant pathways from data that had no significant individual query compounds, its results were congruent with those discovered from transcriptomics data and it detected more pathways than the competing metabolic pathway method did.

    AVAILABILITY: The web server and source code of MPEA are available at http://ekhidna.biocenter.helsinki.fi/poxo/mpea/.

  • 3053.
    Kanold, Philip
    Örebro University, School of Medical Sciences.
    Attempt at quantifying recombinant HIV-1 MPER-epitope using a polypeptide standard2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 3054.
    Kanold, Philip
    Örebro University, School of Medical Sciences.
    The Swedish Standardised Course of Care – Diagnostic Efficacy in Oesophageal and Gastric Cancer2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 3055.
    Kanold, Philip
    et al.
    Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Szabo, Eva
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    van Nieuwenhoven, Michiel A.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    The Swedish Standardized Course of Care-Diagnostic Efficacy in Esophageal and Gastric Cancer2023In: Diagnostics, ISSN 2075-4418, Vol. 13, no 23, article id 3577Article in journal (Refereed)
    Abstract [en]

    Fast-track pathways for diagnosing esophageal or gastric cancer (EGC) have been implemented in several European countries. In Sweden, symptoms such as dysphagia, early satiety, and other alarm symptoms call for a referral for gastroscopy, according to the Swedish Standardized Course of Care (SCC). The aim of this study was to evaluate the diagnostic yield of the SCC criteria for EGC, to review all known EGC cases in Region Örebro County between March 2017 and February 2021, and to compare referral indication(s), waiting times, and tumor stage. In our material, EGC was found in 6.2% of the SCC referrals. Esophageal dysphagia had a positive predictive value (PPV) of 5.6%. The criterion with the highest PPV for EGC was suspicious radiological findings, with a PPV of 24.5%. A total of 139 EGCs were diagnosed, 99 (71%) through other pathways than via the SCC. Waiting times were approximately 14 days longer for patients evaluated via non-SCC pathways. There was no statistically significant association between referral pathway and primary tumor characteristics. The results show that a majority of the current SCC criteria are poor predictors of EGC, and some alarm symptoms lack a sufficiently specific definition, e.g., dysphagia. Referral through this fast track does not seem to have a positive impact on disease outcomes.

  • 3056.
    Kantor, Elizabeth D.
    et al.
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Giovannucci, Edward L.
    Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
    Valdimarsdottir, Unnur A.
    Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA; Center of Public Health Sciences, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Signorello, Lisa B.
    Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Department of Epidemiology and Public Health, University College London, London, United Kingdom; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality2019In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 173, no 11, p. 1095-1097Article in journal (Refereed)
  • 3057.
    Kantor, Elizabeth D.
    et al.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Signorello, Lisa B.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Giovannucci, Edward L.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Nutrition, Harvard School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, USA.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Research Department of Epidemiology and Public Health, University College London, London, United Kingdom; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Epidemiology, Harvard School of Public Health, Boston, USA; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 8, p. 1289-1295Article in journal (Refereed)
    Abstract [en]

    Objective: Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16-20 years).

    Design: At the time of the conscription assessment (1969-1976), height and weight were measured and ESR was assayed. By linkage to the national cancer registry, these conscripts were followed for CRC through 1 January 2010. Over an average of 35 years of follow-up, 885 cases of CRC occurred, including 501 colon cancers and 384 rectal cancers. Cox regression was used to estimate adjusted HRs and corresponding 95% CIs.

    Results: Compared with normal weight (BMI 18.5 to <25 kg/m(2)) in late adolescence, upper overweight (BMI 27.5 to <30 kg/m(2)) was associated with a 2.08-fold higher risk of CRC (95% CI 1.40 to 3.07) and obesity (BMI 30+ kg/m(2)) was associated with a 2.38-fold higher risk of CRC (95% CI 1.51 to 3.76) (p-trend: <0.001). Male adolescents with ESR (15+ mm/h) had a 63% higher risk of CRC (HR 1.63; 95% CI 1.08 to 2.45) than those with low ESR (<10 mm/h) (p-trend: 0.006). Associations did not significantly differ by anatomic site.

    Conclusions: Late-adolescent BMI and inflammation, as measured by ESR, may be independently associated with future CRC risk. Further research is needed to better understand how early-life exposures relate to CRC.

  • 3058.
    Kapetanaki, Stefania
    et al.
    Örebro University, School of Medical Sciences. Nephrology Department, Karolinska University Hospital, Solna, Sweden; Nephrology Department, Karolinska University Hospital, Huddinge, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Medical Sciences.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 21, article id 11864Article in journal (Refereed)
    Abstract [en]

    Trimethylamine N-oxide (TMAO), a product of gut microbiota metabolism, has previously been shown to be implicated in chronic kidney disease. A high TMAO-containing diet has been found to cause tubulointerstitial renal fibrosis in mice. However, today there are no data linking specific molecular pathways with the effect of TMAO on human renal fibrosis. The aim of this study was to investigate the fibrotic effects of TMAO on renal fibroblasts and to elucidate the molecular pathways involved. We found that TMAO promoted renal fibroblast activation and fibroblast proliferation via the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 signaling. We also found that TMAO increased the total collagen production from renal fibroblasts via the PERK/Akt/mTOR pathway. However, TMAO did not induce fibronectin or TGF-β1 release from renal fibroblasts. We have unraveled that the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 mediates TMAO's fibrotic effect on human renal fibroblasts. Our results can pave the way for future research to further clarify the molecular mechanism behind TMAO's effects and to identify novel therapeutic targets in the context of chronic kidney disease.

  • 3059.
    Kapetanaki, Stefania
    et al.
    Örebro University, School of Medical Sciences. Nephrology Department, Karolinska University Hospital, Huddinge, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Medical Sciences.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    TMAO Suppresses Megalin Expression and Albumin Uptake in Human Proximal Tubular Cells Via PI3K and ERK Signaling2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 16, article id 8856Article in journal (Refereed)
    Abstract [en]

    Trimethylamine-N-oxide (TMAO) is a uremic toxin, which has been associated with chronic kidney disease (CKD). Renal tubular epithelial cells play a central role in the pathophysiology of CKD. Megalin is an albumin-binding surface receptor on tubular epithelial cells, which is indispensable for urine protein reabsorption. To date, no studies have investigated the effect of TMAO on megalin expression and the functional properties of human tubular epithelial cells. The aim of this study was first to identify the functional effect of TMAO on human renal proximal tubular cells and second, to unravel the effects of TMAO on megalin-cubilin receptor expression. We found through global gene expression analysis that TMAO was associated with kidney disease. The microarray analysis also showed that megalin expression was suppressed by TMAO, which was also validated at the gene and protein level. High glucose and TMAO was shown to downregulate megalin expression and albumin uptake similarly. We also found that TMAO suppressed megalin expression via PI3K and ERK signaling. Furthermore, we showed that candesartan, dapagliflozin and enalaprilat counteracted the suppressive effect of TMAO on megalin expression. Our results may further help us unravel the role of TMAO in CKD development and to identify new therapeutic targets to counteract TMAOs effects.

  • 3060.
    Karakatsanis, Andreas
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Breast Unit, Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Charalampoudis, Petros
    Oncoplastic Breast Unit, University College London Hospitals, London, UK.
    Pistioli, Lida
    Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Di Micco, Rosa
    Breast Unit, San Raffaele University Hospital, Milan, Italy.
    Foukakis, Theodoros
    Department of Oncology-Pathology, Karolinska Institute Stockholm, Stockholm, Sweden; Breast Centre, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Oncology.
    Axillary evaluation in ductal cancer in situ of the breast: challenging the diagnostic accuracy of clinical practice guidelines2021In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 108, no 9, p. 1120-1125Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Staging of the axilla is not routine in ductal cancer in situ (DCIS) although invasive cancer is observed in 20-25 per cent of patients at final pathology. Upfront sentinel lymph node dissection (SLND) is advocated in clinical practice guidelines in certain situations. These include expected challenges in subsequent SLN detection and when the risk for invasion is high. Clinical practice guidelines are, however, inconsistent and lead to considerable practice variability.

    METHODS: Clinical practice guidelines for upfront SLND in DCIS were identified and applied to patients included in the prospective SentiNot study. These patients were evaluated by six independent, blinded raters. Agreement statistics were performed to assess agreement and concordance. Receiver operating characteristic curves were constructed, to assess guideline accuracy in identifying patients with underlying invasion.

    RESULTS: Eight guidelines with relevant recommendations were identified. Interobserver agreement varied greatly (kappa: 0.23-0.9) and the interpretation as to whether SLND should be performed ranged from 40-90 per cent and with varying concordance (32-88 per cent). The diagnostic accuracy was low with area under the curve ranging from 0.45 to 0.55. Fifty to 90 per cent of patients with pure DCIS would undergo unnecessary SLNB, whereas 10-50 per cent of patients with invasion were not identified as 'high risk'. Agreement across guidelines was low (kappa = 0.24), meaning that different patients had a similar risk of being treated inaccurately.

    CONCLUSION: Available guidelines are inaccurate in identifying patients with DCIS who would benefit from upfront SLNB. Guideline refinement with detailed preoperative work-up and novel techniques for SLND identification could address this challenge and avoid overtreatment.

  • 3061.
    Karakatsanis, Andreas
    et al.
    Department for Surgical Sciences, Faculty of Medicine, Uppsala University and Section for Breast Surgery, Uppsala University Hospital, Uppsala, Sweden.
    Foukakis, Theodoros
    Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Per
    Sahlgrenska Academy / Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mamounas, Eleftherios
    Orlando Health UF Health Cancer Center, Orlando FL, USA.
    Chagpar, Anees
    Yale University School of Medicine, New Haven CT, USA.
    Boyages, John
    Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
    Rubio, Isabel
    Navarra University Clinic, Madrid, Spain.
    Naume, Bjørn
    Oslo University Hospital, Oslo, Norway.
    Mauri, Davide
    Faculty of Medicine, University of Ioannina, Ioannina, Greece.
    van der Wall, Elsken
    University Medical Center Utrecht, Utrecht, Netherlands.
    Shah, Chirag
    Taussig Cancer Institute, Cleveland Clinic, Cleveland OH, USA.
    Kwong, Ava
    The University of Hong Kong, Queen Mary and Tung Wah Hospital and The University of Hong Kong-ShenZhen Hospital, Hong Kong.
    McAuliffe, Priscilla
    Women's Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh, UPMC Hillman Cancer Center, Division of Surgical Oncology, Department of Surgery, Pittsburgh PA, USA.
    Gentilini, Oreste
    IRCCS San Raffaele, Milan, Italy.
    Ignatiadis, Michail
    Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium.
    Schlichting, Ellen
    Oslo University Hospital, Oslo, Norway.
    Zgajnar, Janez
    Institute of Oncology Ljubljana, Ljubljana, Slovenia.
    Meani, Francesco
    Lugano Hospital, Lugano, Switzerland.
    Tasoulis, Marios Konstantinos
    Royal Marsden Hospital, London, United Kingdom.
    Whitworth, Pat
    Nashville Breast Center, Nashville TN, USA.
    Weber, Walter
    Basel University Hospital, Basel, Switzerland.
    Charalampoudis, Petros
    University College London Hospitals, London, United Kingdom.
    Gulluoglu, Bahadir
    Marmara University Hospital, Istanbul, Turkey.
    Pistioli, Lida
    Institute of Clinical Sciences- Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Tvedskov, Tove Filtenborg
    Rigshospitalet, Copenhagen, Denmark.
    Leidenius, Marjut
    Helsinki University Central Hospital, Helsinki, Finland.
    Mann, Bruce
    The University of Melbourne, Melbourne, Australia.
    Witkamp, Arjen
    University Medical Center Utrecht, Utrecht, Netherlands.
    Wyld, Lynda
    University of Sheffield, Sheffield, United Kingdom.
    di Micco, Rosa
    IRCCS San Raffaele, Milan, Italy.
    Markopoulos, Christos
    National and Kapodistrian University, Athens, Greece.
    Valachis, Antonis
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wärnberg, Fredrik
    Uppsala University, Uppsala, Sweden.
    Axillary Staging in the Setting of a Preoperative Diagnosis of Ductal Cancer In Situ (DCIS): Results of an International Expert Panel and a Critical Guideline Performance Using Frequentist and Bayesian Analysis2020In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 27, no Suppl. 2, p. S337-S338Article in journal (Other academic)
    Abstract [en]

    Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB.

    Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion.

    Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB in 41.3/61.4%, whereas individual rates ranged from 11 to 100%. Agreement among panelists was low (kappa=0.37). In multivariate regression analysis for the entire panel, type of surgery was the most common determinant, (simple WLE=less, OPBCS=more and Mx=constant for SLNB), followed by symptomatic diagnosis and DCIS size. Most (26) members had a clear decision-making pattern regarding SLND, based mainly on DCIS size and type of surgery. Individual decision-making performed modestly in identifying patients with underlying invasion (AUC range 0,47-0,59), resulting mainly in overtreatment in 44-77% of patients. The panel performed similarly by majority (AUC 0,5) and by consensus (AUC 0,55) but “undertreated” 60-75% of patients with invasion, failing to identify them as "high-risk." After the recognition of different decision-making patterns, panelists were divided in subgroups with similar decision-making pattern. Analysis identified subgroups with difference in SLNB rate but not with better AUC. The disagreement among panelists in the same subgroups was significant, not only regarding which patients should undergo SLNB, but also on what factors that recommendation was based on. Eight guidelines with relevant recommendations were identified [USA (ASCO/NCCN), Europe (ESMO), Sweden, Denmark, UK, Netherlands and Italy, retrieval date May 2019]. Agreement among raters for each guideline separately varied (kappa: 0.23-0.9). Interpretation as to whether SLNB should be performed ranged widely (40-90%) and with varying concordance (32-88%). No guideline demonstrated accuracy (AUC range 0.45-0.55). Overtreatment risk was high (50-90%), whereas 10-50% of patients with invasion were not identified as “high- risk.” Agreement across guidelines was low (kappa=0.24), meaning that different patients had similar risk to be treated inaccurately, regardless of which guideline was examined.

    Conclusions: Individualized decision-making and guideline interpretation may be highly subjective and with low accuracy in terms of prediction of invasive disease, resulting in almost random risk for over- or undertreatment of the axilla in patients with DCIS. This suggests that current views and guidelines should be challenged. More accurate preoperative workup and novel techniques to allow for delayed SLNB may be of value in this setting.

  • 3062.
    Karapanagioti, A.
    et al.
    1st Department of Propaupeudic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Nasiri-Ansari, N.
    Department of BiologicalChemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Vachou, E.
    Department of Gastroenterology, Army Share Fund Hospital (NIMTS), Athens, Greece.
    Kyriakopoulos, G.
    Department of Pathology, Evaggelismos Hospital, Athens, Greece.
    Kassi, E.
    Department of BiologicalChemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Kaltsas, G.
    1st Department of Propaupeudic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Aberrant expression pattern of circadian clock genes in type 1 gastric neuroendocrine neoplasms compared to ECL-cell hyperplasia2021In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 33, no S1, p. 37-37Article in journal (Other academic)
    Abstract [en]

    Introduction: There is a continuity of changes from ECL-cell hyperplasia to type 1 gastric neuroendocrine neoplasms (GNEN1) development with important clinical implications.  

    Aim(s): Although the effect of the circadian clock system on neuroendocrine tumorigenesis has been addressed, the role of the peripheral clock system in the transition from ECL-cell hyperplasia to GNEN1 remains to be explored.

    Materials and methods: Six GNEN1 patients and 10 patients with ECL-cell hyperplasia were included. Blood samples were collected at 8 am, 3pm and 10pm for peripheral blood mononuclear  ells (PBMCs) isolation. The mRNA expression of clock-related genes (CLOCK, BMAL1, CRY-1, PER2, ROR-α and REV-ERBβ) were evaluated by real-time quantitative PCR from PBMCs.  

    Results: In GNEN1 patients, BMAL genes where lower expressed at night than early in the morning (p=0.02), whereas patients with ECL-cell hyperplasia expressed lower levels of PER2 and REV-ERBβ (p=0.03 and p=0.05,respectively). In addition, GNEN1 patients expressed lower levels of CLOCK, PER2 and REV-ERBβ in the early evening than in the morning (p=0.04; p=0.03; p=0.05, respectively). When comparing the two groups (GNEN1 vs. ECL-cell hyperplasia) at the three different time points, a marginal increase in CLOCK, PER2 and REV-ERBβ expression early in the morning (p=0.06, 0.02 and 0.07, respectively) along with a marginal increase in REV-ERBβ and BMAL expression in the early evening (p=0.09 and p=0.08, respectively) and a marginal increase in BMAL at night (p=0.09) in GNEN1 patients was observed.

    Conclusion: Our findings point towards an upregulated expression of clock-related genes in patients with GNEN1 as compared to ECL-cell hyperplasia, suggesting  a possible involvement in GNEN1 tumorigenesis that needs to be confirmed in a larger patients group.

  • 3063.
    Kardeby, Caroline
    Örebro University, School of Medical Sciences.
    Studies of platelet signalling and endothelial cell responses using unique synthetic drugs2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Haemostasis is a complex and tightly regulated process which protects us from bleeding. Platelets are essential for maintained haemostasis. Under normal conditions platelets are calmed by antithrombotic substances release by the endothelium. During vascular injury, the platelets will activate and form a haemostatic plug to prevent bleeding. Inflammatory processes like atherosclerosis can disturb the haemostatic balance and lead to severe consequences like myocardial infarction and stroke. Inhibition of platelets and coagulation are common treatments to prevent unwanted blood clot formation. There is a great need for increased knowledge on the mechanisms of thrombosis and characterisation of new substances with possible therapeutic potential. This thesis used unique synthetic drugs to study platelet signalling and endothelial responses. Paper I showed that both sulfated polysaccharides from seaweed and synthetic glycopolymers which mimic their chemical properties caused platelet activation.

    Paper II elucidated the molecular mechanism underlying platelet activation by sulfated glycopolymers and polysaccharides. We found that human platelet activation took place via the Platelet endothelial aggregation receptor 1 (PEAR1), while mouse platelet activation was mainly via C-type lectin-like receptor 2. Aggregation was supported by Glycoprotein Ibα in both species.

    Paper III showed the effect of synthetic glycopolymers and natural polysaccharides on cultured human endothelial cells. We found that both the glycopolymers and polysaccharides caused a proinflammatory response after 24h.

    In Paper IV, the effect of a synthetic purine analogue with a nitrate ester motif was studied. We found that the purine analogue reduced platelet functions by inhibiting Rho-associated protein kinase (ROCK).

    This thesis describes unique synthetic drugs that can be used for further studies of the mechanisms underlying the biological processes of thrombosis and inflammation. The synthetic glycopolymers can be used to further elucidate the physiological role of PEAR1, a potential future therapeutic target.

    List of papers
    1. Fucoidan-Mimetic Glycopolymers as Tools for Studying Molecular and Cellular Responses in Human Blood Platelets
    Open this publication in new window or tab >>Fucoidan-Mimetic Glycopolymers as Tools for Studying Molecular and Cellular Responses in Human Blood Platelets
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    2017 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, no 2, article id UNSP 1600257Article in journal (Refereed) Published
    Abstract [en]

    The marine sulfated polysaccharide fucoidan displays superior ability to induce platelet aggregation compared to other sulfated polysaccharides. As such, it is an attractive tool for studying molecular and cellular responses in activated platelets. The heterogeneous structure, however, poses a problem in such applications. This study describes the synthesis of sulfated α-l-fucoside-pendant poly(methacryl amides) with homogeneous structures. By using both thiol-mediated chain transfer and reversible addition-fragmentation chain transfer polymerization techniques, glycopolymers with different chain lengths are obtained. These glycopolymers show platelet aggregation response and surface changes similar to those of fucoidan, and cause platelet activation through intracellular signaling as shown by extensive protein tyrosine phosphorylation. As the platelet activating properties of the glycopolymers strongly mimic those of fucoidan, this study concludes these fucoidan-mimetic glycopolymers are unique tools for studying molecular and cellular responses in human blood platelets.

    Place, publisher, year, edition, pages
    Weinheim, Germany: Wiley-VCH Verlagsgesellschaft, 2017
    Keywords
    biological applications of polymers; biomimetic; radical polymerization; reversible addition fragmentation chain transfer; structure-property relations
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:oru:diva-52179 (URN)10.1002/mabi.201600257 (DOI)000394592600012 ()27616165 (PubMedID)2-s2.0-84987653303 (Scopus ID)
    Note

    Funding Agency:

    AFA Insurance, VR Treatments of the Future grant

    Available from: 2016-09-21 Created: 2016-09-14 Last updated: 2019-05-06Bibliographically approved
    2. Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbα
    Open this publication in new window or tab >>Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbα
    Show others...
    2019 (English)In: Blood Advances, ISSN 2473-9529 , E-ISSN 2473-9537, Vol. 3, no 3, p. 275-287Article in journal (Refereed) Published
    Abstract [en]

    Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)-dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1). Synthetic glycopolymers and natural fucoidan stimulate marked phosphorylation of PEAR1 and Akt, but not Syk. Platelet aggregation and Akt phosphorylation induced by natural fucoidan and synthetic glycopolymers are blocked by a monoclonal antibody to PEAR1. Direct binding of sulfated glycopolymers to epidermal like growth factor (EGF)-like repeat 13 of PEAR1 was shown by avidity-based extracellular protein interaction screen technology. In contrast, synthetic glycopolymers and natural fucoidans activate mouse platelets through a Src- and Syk-dependent pathway regulated by C-type lectin-like receptor 2 (CLEC-2) with only a minor role for PEAR1. Mouse platelets lacking the extracellular domain of GPIbα and human platelets treated with GPIbα-blocking antibodies display a reduced aggregation response to synthetic glycopolymers. We found that synthetic sulfated glycopolymers bind directly to GPIbα, substantiating that GPIbα facilitates the interaction of synthetic glycopolymers with CLEC-2 or PEAR1. Our results establish PEAR1 as the major signaling receptor for natural fucose-based polysaccharides and synthetic glycopolymers in human, but not in mouse, platelets. Sulfated α-l-fucoside-pendant glycopolymers are unique tools for further investigation of the physiological role of PEAR1 in platelets and beyond.

    Place, publisher, year, edition, pages
    American Society of Hematology, 2019
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Hematology
    Identifiers
    urn:nbn:se:oru:diva-72478 (URN)10.1182/bloodadvances.2018024950 (DOI)000458442500007 ()30700416 (PubMedID)2-s2.0-85060943358 (Scopus ID)
    Funder
    Knowledge Foundation
    Note

    Funding Agencies:

    BHF  PG/16/53/32242  RG/13/18/30563 

    Deutsche Forschungsgemeinschaft  DFG: Eb 177/14-1 

    Fonds voor Wetenschappelijk Onderzoek Vlaanderen grant  G0A6514N 

    Available from: 2019-02-14 Created: 2019-02-14 Last updated: 2024-03-06Bibliographically approved
    3. Sulfated glycopolymers and polysaccharides regulate inflammation-related proteins in human vascular endothelial cells
    Open this publication in new window or tab >>Sulfated glycopolymers and polysaccharides regulate inflammation-related proteins in human vascular endothelial cells
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-74033 (URN)
    Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-05-06Bibliographically approved
    4. A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition
    Open this publication in new window or tab >>A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-74034 (URN)
    Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-05-06Bibliographically approved
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  • 3064.
    Kardeby, Caroline
    et al.
    Örebro University, School of Medical Sciences.
    Fälker, Knut
    Örebro University, School of Medical Sciences.
    Haining, Elizabeth J.
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
    Criel, Maarten
    Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
    Lindkvist, Madelene
    Örebro University, School of Medical Sciences.
    Barroso, Ruben
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom.
    Påhlsson, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ljungberg, Liza
    Örebro University, School of Medical Sciences.
    Tengdelius, Mattias
    Division of Organic Chemistry, Linköping University, Linköping, Sweden.
    Rainger, G. Ed.
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
    Watson, Stephanie
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
    Eble, Johannes A.
    Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
    Hoylaerts, Marc F.
    Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
    Emsley, Jonas
    Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom; Division of Biomolecular Science and Medicinal Chemistry, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
    Konradsson, Peter
    Division of Organic Chemistry, Linköping University, Linköping, Sweden.
    Watson, Steve P.
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom.
    Sun, Yi
    Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom.
    Grenegård, Magnus
    Örebro University, School of Medical Sciences.
    Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbα2019In: Blood Advances, ISSN 2473-9529 , E-ISSN 2473-9537, Vol. 3, no 3, p. 275-287Article in journal (Refereed)
    Abstract [en]

    Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)-dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1). Synthetic glycopolymers and natural fucoidan stimulate marked phosphorylation of PEAR1 and Akt, but not Syk. Platelet aggregation and Akt phosphorylation induced by natural fucoidan and synthetic glycopolymers are blocked by a monoclonal antibody to PEAR1. Direct binding of sulfated glycopolymers to epidermal like growth factor (EGF)-like repeat 13 of PEAR1 was shown by avidity-based extracellular protein interaction screen technology. In contrast, synthetic glycopolymers and natural fucoidans activate mouse platelets through a Src- and Syk-dependent pathway regulated by C-type lectin-like receptor 2 (CLEC-2) with only a minor role for PEAR1. Mouse platelets lacking the extracellular domain of GPIbα and human platelets treated with GPIbα-blocking antibodies display a reduced aggregation response to synthetic glycopolymers. We found that synthetic sulfated glycopolymers bind directly to GPIbα, substantiating that GPIbα facilitates the interaction of synthetic glycopolymers with CLEC-2 or PEAR1. Our results establish PEAR1 as the major signaling receptor for natural fucose-based polysaccharides and synthetic glycopolymers in human, but not in mouse, platelets. Sulfated α-l-fucoside-pendant glycopolymers are unique tools for further investigation of the physiological role of PEAR1 in platelets and beyond.

  • 3065.
    Kardeby, Caroline
    et al.
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Paramel Varghese, Geena
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Pournara, Dimitra
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Fotopoulou, Theano
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Sirsjö, Allan
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Koufaki, Maria
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Fransén, Karin
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Grenegård, Magnus
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibitionManuscript (preprint) (Other academic)
  • 3066.
    Kardeby, Caroline
    et al.
    Örebro University, School of Medical Sciences.
    Paramel Varghese, Geena
    Örebro University, School of Medical Sciences.
    Pournara, Dimitra
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Fotopoulou, Theano
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Sirsjö, Allan
    Örebro University, School of Medical Sciences.
    Koufaki, Maria
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
    Fransén, Karin
    Örebro University, School of Medical Sciences.
    Grenegård, Magnus
    Örebro University, School of Medical Sciences.
    A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition2019In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 857, article id 172428Article in journal (Refereed)
    Abstract [en]

    Natural purines like ATP, ADP and adenosine have crucial roles in platelet physiology. This knowledge has been significant in drug development and today ADP receptor antagonists are widely used for prevention of thrombotic events following myocardial infarction and ischaemic stroke.

    Recent studies have shown that a purine analogue bearing nitrate ester group (denoted MK128) has anti-inflammatory effects probably due to its ability to donate nitric oxide (NO). However, other pharmacological mechanisms may contribute to the observed effect. The aim of the present study was to establish the anti-platelet activity and elucidate the underlying molecular mechanism(s) of the purine analogue MK128.

    We found that MK128 reduced aggregation and secretion induced by the thrombin receptor agonist SFLLRN and nearly abolished aggregation and secretion induced by thromboxane A2 (TxA2) and collagen receptor agonists. The inhibition took place despite blockage of the NO/cGMP signalling system. Furthermore, interaction between MK128 and platelet purinergic receptors did not explain the observed inhibition. Instead, we found that MK128 concentration-dependently inhibited Rho-associated kinase (ROCK), which led to decreased ROCK-dependent myosin phosphatase target subunit (MYPT)-1 phosphorylation and suppression of platelet functional responses.

  • 3067.
    Kardeby, Caroline
    et al.
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Sirsjö, Allan
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Ljungberg, Liza
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Grenegård, Magnus
    Örebro University, School of Medical Sciences. Cardiovascular Research Centre (CVRC).
    Sulfated glycopolymers and polysaccharides regulate inflammation-related proteins in human vascular endothelial cellsManuscript (preprint) (Other academic)
  • 3068.
    Karefylakis, Christos
    Örebro University, School of Medical Sciences.
    Vitamin D and its role in obesity and other associated conditions2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Vitamin D has received much attention in recent years due to the re-emergence of vitamin D deficiency as a global health issue along with increasing evidence indicating that 1,25-dihydroxivitamin D, the hormonally active form of vita-min D, not only acts in calcium and bone metabolism but also generates ex-traskeletal biological responses.

    In this thesis, the role of vitamin D in obesity and other associated condi-tions has been studied.

    In paper 1, the prevalence of vitamin D deficiency and secondary hyperpara-thyroidism over the long term after Roux-en-Y gastric bypass (RYGB) were evaluated. We found a substantial prevalence of vitamin D deficiency and secondary hyperparathyroidism after RYGB, whereas calcium levels remained within normal range. An expected improvement in vitamin D status after weight loss could have been countered by the malabsorption induced by surgery.

    In paper 2, the prevalence of anemia and related deficiencies over the long term after RYGB were studied. We found that 27% of the patients had anemia postoperatively, 20% had iron deficiency, 12% had folate deficiency and 2% had vitamin B12 deficiency. Anemia was mainly due to iron deficiency, and its frequency did not seem to progress with time after surgery.

    In paper 3, the effects of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men with vitamin D deficiency at baseline were investigated. No statistically significant difference between the placebo and the intervention group regarding changes in percentage body fat, maximum oxygen uptake, BMI and maximum load was found.

    In paper 4, the prevalence and determinants of 3-epi-25(OH)D3 were exam-ined. 3-epi-25(OH)D3 was detected in 7.7% of the study population and the mean concentration was 8.4 nmol/L. The quantification of 3-epi-25(OH)D3 would not significantly influence the clinical interpretation of vitamin D levels.

    In conclusion, new knowledge about vitamin D is continuously emerging but there is a discrepancy between cross-sectional studies associating low vitamin D levels to obesity and other related metabolic complications and the lack of effects of vitamin D supplementation in clinical trials. Large RCTs with longer duration in obese subjects with baseline vitamin D deficiency are warranted.

    List of papers
    1. Vitamin D Status 10 Years After Primary Gastric Bypass: Gravely High Prevalence of Hypovitaminosis D and Raised PTH Levels
    Open this publication in new window or tab >>Vitamin D Status 10 Years After Primary Gastric Bypass: Gravely High Prevalence of Hypovitaminosis D and Raised PTH Levels
    Show others...
    2014 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 24, no 3, p. 343-348Article in journal (Refereed) Published
    Abstract [en]

    The primary aim of this study was to evaluate the prevalence of vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass. Secondly, we have tried to assess predictors for vitamin D deficiency. Five hundred thirty-seven patients who underwent primary Roux-en-Y gastric bypass surgery between 1993 and 2003 at the A-rebro University Hospital and Uppsala University Hospital were eligible for the study. Patients were asked to provide a blood sample between November 2009 and June 2010 and to complete a questionnaire about their postoperative health status. Serum values of 25-OH vitamin D, parathyroid hormone (PTH), alkaline phosphatase (ALP) and calcium were determined. Follow-up was completed in 293 patients, of which 83 % were female, with an age of 49 +/- 9.9 years after a median time of 11 +/- 2.8 years. Vitamin D, PTH and albumin-corrected calcium values were 42 +/- 20.4 nmol/L, 89.1 +/- 52.7 ng/L and 2.3 +/- 0.1 mmol/L, respectively. Of all patients, 65 % were vitamin D deficient, i.e. 25-OH vitamin D < 50 nmol/L, and 69 % had PTH above the upper normal reference range, i.e. > 73 ng/L. Vitamin D was inversely correlated with PTH levels (p < 0.001) and positively correlated with calcium (p = 0.016). Vitamin D did not correlate with ALP. The only factor found to predict vitamin D deficiency was high preoperative body mass index (BMI) (p = 0.008), whereas gender, age, time after surgery and BMI at follow-up did not. Vitamin D deficiency and secondary hyperparathyroidism after Roux-en-Y gastric bypass (RYGB) were confirmed in our study because 65 % of patients had vitamin D deficiency, and 69 % had increased PTH levels more than 10 years after surgery. These data are alarming and highlight the need for improved long-term follow-up. Vitamin D deficiency does not seem to progress with time after surgery, possibly due to weight loss. Only preoperative BMI, cutoff point 43 kg/m(2), was a predictor of vitamin D deficiency at follow-up. Improved long-term follow-up of patients that undergo RYGB is needed.

    Keywords
    Vitamin D, Gastric bypass, Hyperparathyroidism, Long-term follow-up
    National Category
    Surgery
    Identifiers
    urn:nbn:se:oru:diva-56581 (URN)10.1007/s11695-013-1104-y (DOI)000330983200001 ()24163201 (PubMedID)2-s2.0-84957845106 (Scopus ID)
    Available from: 2017-03-20 Created: 2017-03-20 Last updated: 2024-03-04Bibliographically approved
    2. Prevalence of anemia and related deficiencies 10 years after gastric bypass: a retrospective study
    Open this publication in new window or tab >>Prevalence of anemia and related deficiencies 10 years after gastric bypass: a retrospective study
    Show others...
    2015 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 6, p. 1019-1023Article in journal (Refereed) Published
    Abstract [en]

    Bariatric surgery has gained wide acceptance as treatment for severe obesity and is associated with decreased overall mortality. The aims of this study were to evaluate the prevalence of anemia long term after Roux-en-Y gastric bypass (RYGB) and to search for factors predicting anemia.

    All 745 patients who underwent RYGB between 1993 and 2003 at either A-rebro or Uppsala University Hospital and who were living in Sweden were invited to participate by providing a fasting blood sample and completing a questionnaire about their health status. Full blood count, serum iron, transferrin, vitamin B-12, and folic acid were determined.

    Follow-up was completed in 431 patients (58 %) with mean age 51.3 +/- 10 years. Of all patients, 27 % had anemia postoperatively and related deficiencies; iron, folic acid, and vitamin B-12 were seen in 20, 12, and 2 %, respectively. There was no correlation between anemia and sex, follow-up time, 25-OH vitamin D level, and preoperative or postoperative BMI. An inverse correlation was found between anemia and regular medical checkups concerning gastric bypass surgery.

    Twenty-seven percent of patients had anemia more than 10 years after RYGB. Anemia does not seem to progress with time and was less common in patients with regular medical checkups. Thus, improved long-term follow-up is needed.

    Place, publisher, year, edition, pages
    Springer, 2015
    Keywords
    Gastric bypass, Anemia, Iron deficiency, Long-termfollow-up
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:oru:diva-44899 (URN)10.1007/s11695-014-1500-y (DOI)000354216500010 ()25394588 (PubMedID)2-s2.0-84939978711 (Scopus ID)
    Note

    Funding Agencies:

    Örebro County Council

    Uppsala-Örebro Regional Research Council RFR-32261

    Available from: 2015-06-15 Created: 2015-06-15 Last updated: 2024-03-04Bibliographically approved
    3. Vitamin D C3 epimer in a mid-Swedish region: Analytical measurement and epidemiology
    Open this publication in new window or tab >>Vitamin D C3 epimer in a mid-Swedish region: Analytical measurement and epidemiology
    Show others...
    2018 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 478, p. 182-187Article in journal (Refereed) Published
    Abstract [en]

    Background: The discovery of an epimeric form of 25(OH)D3 may complicate the interpretation of vitamin Dstatus. The aim of this study was to examine the prevalence and determinants of 25-hydroxy-3-epi-vitamin D3 (3- epi-25(OH)D3) in a mid-Swedish region and to investigate how the measurement of 3-epi-25(OH)D3 would affect the assessment of vitamin D status using current thresholds.

    Methods: We conducted a cross-sectional study of 8286 in- and outpatients in primary as well as secondary care settings. Plasma 25(OH)D, 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured using High Pressure Liquid Chromatography – Tandem Mass Spectrometry (HPLC – MS/MS). The relative 3-epi-25(OH)D3 contribution was calculated as a percentage of the total 25(OH)D3. Blood samples were collected between March 2014 and July 2015 providing a seasonal aspect to the results.

    Results: 3-epi-25(OH)D3was detected in 635 cases (7.7% of all subjects), and the mean concentration was8.4 ± 3.5 nmol/L. 3-epi-25(OH)D3correlated significantly with 25(OH)D3(r =0.38, p < 0.001).A multivariateanalysis among the detected showed that male gender and winter season were independently associatedwith higher 3-epi-25(OH)D3/25(OH)D3percentage ratio (R2=0.044). Infants and children had a significantlyhigher detection rate compared to the reference age category (18–45 years) as well as those who were testedduring the summer season.

    Conclusions: We report findings from the first epidemiologic study of 3-epi-25(OH)D3 conducted in Sweden, based on a large population sample. 3-epi-25(OH)D3 was detected in 7.7% of the study population and the mean concentration was 8.4 nmol/L. The quantification of 3-epi-25(OH)D3 would not significantly influence the clinical interpretation of vitamin D levels. Additional studies are needed to understand the metabolic pathway and the possible physiological functions of this metabolite.

    Place, publisher, year, edition, pages
    Amsterdam, Netherlands: Elsevier, 2018
    Keywords
    3-epi 25(OH)D(3), 25(OH)D(3), High Pressure Liquid Chromatography – Tandem Mass Spectrometry (HPLC – MS/MS), Vitamin D
    National Category
    Biomedical Laboratory Science/Technology
    Identifiers
    urn:nbn:se:oru:diva-64072 (URN)10.1016/j.cca.2018.01.002 (DOI)000425070000028 ()29305842 (PubMedID)2-s2.0-85040024242 (Scopus ID)
    Note

    Funding Agency:

    Örebro University  ALF 2016:1 OLL-615521

    Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2024-03-04Bibliographically approved
    4. Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men: A randomized controlled trial
    Open this publication in new window or tab >>Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men: A randomized controlled trial
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-66214 (URN)
    Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2024-03-04Bibliographically approved
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  • 3069.
    Karefylakis, Christos
    et al.
    Örebro University, School of Medical Sciences.
    Ariander, AnnaClara
    Rask, Peter
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Särnblad, Stefan
    Örebro University, School of Medical Sciences.
    Rask, Eva
    Region Örebro län, Örebro.
    Effect of Vitamin D supplementation on body composition in overweight men: A randomized controlled trial2017Conference paper (Refereed)
  • 3070.
    Karefylakis, Christos
    et al.
    Örebro University, School of Medical Sciences.
    Petterson Pablo, Paul
    Örebro University Hospital, Örebro, Sweden.
    Särnblad, Stefan
    Örebro University, School of Medical Sciences.
    Rask, Eva
    Örebro University Hospital, Örebro, Sweden.
    Eriksson, Clas-Göran
    D-vitamin C3-epimer. Metodbeskrivning och epidemiologisk studie i en mellansvensk region.2017Conference paper (Refereed)
  • 3071.
    Karefylakis, Christos
    et al.
    Örebro University, School of Medical Sciences. Department of Endocrinology.
    Pettersson-Pablo, Paul
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Särnblad, Stefan
    Örebro University, School of Medical Sciences. Department of Pediatrics.
    Rask, Eva
    Department of Endocrinology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bitar, Manar
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Magnusson, Anders
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Eriksson, Clas-Göran
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Vitamin D C3 epimer in a mid-Swedish region: Analytical measurement and epidemiology2018In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 478, p. 182-187Article in journal (Refereed)
    Abstract [en]

    Background: The discovery of an epimeric form of 25(OH)D3 may complicate the interpretation of vitamin Dstatus. The aim of this study was to examine the prevalence and determinants of 25-hydroxy-3-epi-vitamin D3 (3- epi-25(OH)D3) in a mid-Swedish region and to investigate how the measurement of 3-epi-25(OH)D3 would affect the assessment of vitamin D status using current thresholds.

    Methods: We conducted a cross-sectional study of 8286 in- and outpatients in primary as well as secondary care settings. Plasma 25(OH)D, 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured using High Pressure Liquid Chromatography – Tandem Mass Spectrometry (HPLC – MS/MS). The relative 3-epi-25(OH)D3 contribution was calculated as a percentage of the total 25(OH)D3. Blood samples were collected between March 2014 and July 2015 providing a seasonal aspect to the results.

    Results: 3-epi-25(OH)D3was detected in 635 cases (7.7% of all subjects), and the mean concentration was8.4 ± 3.5 nmol/L. 3-epi-25(OH)D3correlated significantly with 25(OH)D3(r =0.38, p < 0.001).A multivariateanalysis among the detected showed that male gender and winter season were independently associatedwith higher 3-epi-25(OH)D3/25(OH)D3percentage ratio (R2=0.044). Infants and children had a significantlyhigher detection rate compared to the reference age category (18–45 years) as well as those who were testedduring the summer season.

    Conclusions: We report findings from the first epidemiologic study of 3-epi-25(OH)D3 conducted in Sweden, based on a large population sample. 3-epi-25(OH)D3 was detected in 7.7% of the study population and the mean concentration was 8.4 nmol/L. The quantification of 3-epi-25(OH)D3 would not significantly influence the clinical interpretation of vitamin D levels. Additional studies are needed to understand the metabolic pathway and the possible physiological functions of this metabolite.

  • 3072.
    Karefylakis, Christos
    et al.
    Örebro University, School of Medical Sciences.
    Särnblad, Stefan
    Örebro University, School of Medical Sciences.
    Ariander, Annaclara
    Örebro University, School of Medical Sciences.
    Ehlersson, Gustaf
    Örebro University, School of Medical Sciences.
    Rask, Eva
    Örebro University, School of Medical Sciences. Department of Endocrinology.
    Rask, Peter
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men: A randomized controlled trialManuscript (preprint) (Other academic)
  • 3073.
    Karefylakis, Christos
    et al.
    Department of Endocrinology, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Särnblad, Stefan
    Örebro University, School of Medical Sciences. Department of Pediatrics.
    Ariander, Annaclara
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ehlersson, Gustaf
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rask, Eva
    Örebro University, School of Medical Sciences. Department of Endocrinology.
    Rask, Peter
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Clinical Physiology.
    Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men: a randomized controlled trial2018In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 61, no 3, p. 388-397Article in journal (Refereed)
    Abstract [en]

    Purpose: Several observational studies have shown an association between vitamin D deficiency and non-skeletal major health issues including impaired cardiorespiratory fitness and adiposity. Only a few studies have examined the impact of vitamin D supplementation on these conditions and the results are ambiguous. The aim of this study was to examine the effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight/obese men with vitamin D deficiency.

    Methods: This study was a prospective, placebo controlled, double blinded, randomized trial with a study period of 6 months. Forty overweight/obese men (BMI > 25 kg/m2) with vitamin D deficiency (25(OH)D ≤ 55 nmol/L) were randomized to receive either 2000 IU Cholecalciferol drops or the equivalent amount of drops of placebo. At baseline and follow up body composition and cardiorespiratory fitness were measured and blood samples were obtained. Body composition was measured using bioelectrical impedance analysis (BIA) and cardiorespiratory fitness using cardiopulmonary exercise test (CPET). The primary outcomes were changes in percentage body fat and in maximum oxygen uptake (VO2max).

    Results: No statistically significant difference between the placebo and the intervention group regarding changes in percentage body fat (p = 0.54) and VO2max (p = 0.90) was observed. Moreover, there was no statistically significant difference between the groups concerning changes in BMI (p = 0.26), maximum load (p = 0.89) and oxygen uptake at anaerobic threshold (AT) (p = 0.14).

    Conclusions: We conclude that treatment with 2000 IU/d vitamin D for 6 months does not impact body composition or maximum oxygen uptake in overweight/obese men with vitamin D deficiency.

  • 3074.
    Karihtala, P.
    et al.
    Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
    Valachis, A
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept. of Oncology.
    Tuxen, M.
    Oncology, Herlev and Gentofte Hospital, Herlev, Denmark.
    Geisler, J.
    Oncology Dept., Akershus universitetssykehus HF, Lorenskog, Norway.
    Current treatment landscape of HR+/HER2-advanced breast cancer in the Nordics: A modified Delphi study2022In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 33, no Suppl. 3, p. S218-S218Article in journal (Other academic)
    Abstract [en]

    Background: The aim of this Delphi study was to assess current perspectives on HR+/HER2- advanced breast cancer (aBC) treatment strategies among Nordic BC oncologists, and to gain broader understanding of the uptake and implementation of novel treatments.

    Methods: A modified, three round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection and questionnaires development. The questionnaires covered clinically relevant topics related to HR+/HER2- aBC treatment: treatment patterns in different lines of therapy (first- (1L), second- (2L) and third-line (3L)), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement.

    Results: In total 28 panelists participated in the study. In rounds one and two, 14 and 21 questions reached consensuses, respectively. Thirteen non-consensus reaching questions were reposted in round three, where 10 reached consensus. Overall, topics that reached a high consensus level included: treatment approaches in 1L and 2L treatment setting for HR+/HER2- aBC, treatment of oligometastatic disease, visceral crisis and brain metastases, and age-related treatment considerations. No consensus was reached for aspects regarding 3L therapy and de novo aBC. Endocrine therapy (ET) combined with CDK4/6i was the treatment of choice for both 1L and 2L therapy. Regarding implementation of clinical guidelines, a discrepancy was observed between treatments recommended in guidelines and those used in clinical practice, especially in cases where novel treatments were proposed.

    Conclusions: Endocrine therapy combined with a CDK4/6i is the frontline treatment choice for HR+/HER2- aBC in the Nordics. Observed discrepancies between international clinical guidelines and practice are partly due to difference in the availability of novel treatment strategies that might lead to differences in clinical experience in the Nordics. The lack of consensus might reflect limited evidence on these topics and the need for collaborative research efforts. Written on behalf of Nordic Delphi Panellist group.

  • 3075.
    Karlefors, P.
    et al.
    Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Isaksson, H.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Pellas, U.
    Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Fransson, H.
    Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Johansson, K
    Örebro University Hospital. Örebro University, School of Medical Sciences. Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Svensson, M.A.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Orebro Biobank Clinical Research Center University Hospital Orebro, Orebro, Sweden.
    Regional Biobanking of Liquid Based Cytology (LBC) Samples from the Cervical Cancer Screening Program in Sweden2019In: Europe Biobank Week 2019: Abstract book Poster presentations, 2019, p. 83-, article id P8A_19Conference paper (Refereed)
    Abstract [en]

    Background

    Regional healthcare integrated biobanking of liquid based cytology (LBC) of cervical cancer screening (CCS) samples has been ongoing at Örebro Biobank since 2012. Samples from Dalarna-, Värmland and Örebro County are biobanked as are gional collaboration project with the aim of collecting samples covering the introduction of the national human papilloma virus (HPV) vaccination program. This sample collection provides a unique possibility to follow the effect of the vaccination program by, for example, investigating the prevalence of HPV and changes of HPV genotypes over time.

    Methods

    LBC samples are collected using ThinPrep (Hologic) methodology and aliquoted in 96-well plates (500ul) using the Freedom Evo 150 (Tecan) automated robot before long term storage in minus 25C freezers. All information regarding the samples is processed by the regional laboratory information management system LabWare-LIMS™.

    Results

    The sample collection currently holds close to 400 000 samples that have been collected, aliquoted and stored in the same standardized manner. Of the 500ul that is biobanked, 200ul is reserved for the patients’ own care while 300ul is available for research. This population based sample collection includes the majority of agegroups (ranging from 23 to 65+ yrs) which enables genetic-, registry-, methodological and quality studies.

    Discussion

    Several research groups are using this sample collection and numerous papers have been published within the research field. We invite additional research groups to utilize the samples in both national and international collaborations.

  • 3076.
    Karlin, Maria
    Örebro University, School of Medical Sciences.
    Taxaners effektivitet vid recidiverande bröstcancer hos patienter som behandlats med taxaner som neoadjuvant eller adjuvant behandling2020Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Taxaner utgör ett etablerat behandlingsalternativ mot bröstcancer preoperativt, postoperativt och vid recidiv. Det finns även belägg för att taxaner är effektiva vid metastaserad sjukdom hos patienter som tidigare fått taxaner som neo-/adjuvant behandling. Detta är en behandlingsstrategi som mer och mer börjar användas kliniskt. På grund av risk för resistens hos tumören vid återbehandling med samma typ av cytostatika är det viktigt att följa upp resultatet av detta.

    Syfte: Att undersöka taxaners effektivitet vid recidiverande bröstcancer hos patienter som har behandlats med taxaner som neoadjuvant eller adjuvant behandling.

    Metod: En retrospektiv kohortstudie gjordes där patienter med icke-spridd bröstcancer behandlade med neo-/adjuvanta taxaner i Region Örebro Län identifierades och utifrån dem de som fick recidiv mellan åren 2011-2016. Totalt 44 patienter inkluderades i studien. Dessa delades in i olika kohorter: de som fått taxaner som behandling vid recidiv och de som fått icke-taxaner samt i vilken linje dessa behandlingar gavs.

    Resultat: Taxaner gav en ORR på 32% vid första linjens behandling, 44,4% vid andra linjens behandling och 20% som tredje linjens behandling (p = 0,319, 0,194, 0,751 vid jämförelse med icke-taxaner). De gav en progressionsfri tid på 11, 10 och tre månader för respektive linje (p = 0,069, 0,869, 0,360 vid jämförelse med icke-taxaner). Den totala överlevnaden vid behandling med taxaner var i median 25 månader (p = 0,629 vid jämförelse med icke-taxaner).

    Slutsats: Fynden indikerar att taxaner går att använda som behandling vid recidiverande bröstcancer hos patienter som tidigare exponerats för taxaner som neoadjuvant eller adjuvant behandling.

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  • 3077.
    Karlqvist, Sara
    Örebro University, School of Medical Sciences.
    Clinical aspects of biological treatment in inflammatory bowel disease2024Doctoral thesis, comprehensive summary (Other academic)
  • 3078.
    Karlsson, Adam
    Örebro University, School of Medical Sciences.
    Identification of sepsis using SIRS, qSOFA, regression and decision tree analysis2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 3079.
    Karlsson, Adam
    Örebro University, School of Medical Sciences.
    Variables predictive of sepsis mortality: – a cross sectional analysis using machine learning2020Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 3080.
    Karlsson, Adam
    et al.
    Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Stassen, Willem
    Division of emergency Medicine, University of Cape Town, Cape Town, South Africa.
    Loutfi, Amy
    Örebro University, School of Science and Technology.
    Wallgren, Ulrika M.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Science and Education, Karolinska Institutet, Söderssjukhuset, Stockholm, Sweden; Department of Emergency Medicine, Örebro University Hospital and School of Medicine, Örebro University, Örebro, Sweden.
    Larsson, Eric
    Department of Infectious Diseases, Centralsjukhuset, Karlstad, Sweden.
    Kurland, Lisa
    Örebro University, School of Medical Sciences. Department of Emergency Medicine.
    Predicting mortality among septic patients presenting to the emergency department-a cross sectional analysis using machine learning2021In: BMC Emergency Medicine, ISSN 1471-227X, E-ISSN 1471-227X, Vol. 21, no 1, article id 84Article in journal (Refereed)
    Abstract [en]

    Background: Sepsis is a life-threatening condition, causing almost one fifth of all deaths worldwide. The aim of the current study was to identify variables predictive of 7- and 30-day mortality among variables reflective of the presentation of septic patients arriving to the emergency department (ED) using machine learning.

    Methods: Retrospective cross-sectional design, including all patients arriving to the ED at Sodersjukhuset in Sweden during 2013 and discharged with an International Classification of Diseases (ICD)-10 code corresponding to sepsis. All predictions were made using a Balanced Random Forest Classifier and 91 variables reflecting ED presentation. An exhaustive search was used to remove unnecessary variables in the final model. A 10-fold cross validation was performed and the accuracy was described using the mean value of the following: AUC, sensitivity, specificity, PPV, NPV, positive LR and negative LR.

    Results: The study population included 445 septic patients, randomised to a training (n = 356, 80%) and a validation set (n = 89, 20%). The six most important variables for predicting 7-day mortality were: "fever", "abnormal verbal response", "low saturation", "arrival by emergency medical services (EMS)", "abnormal behaviour or level of consciousness" and "chills". The model including these variables had an AUC of 0.83 (95% CI: 0.80-0.86). The final model predicting 30-day mortality used similar six variables, however, including "breathing difficulties" instead of "abnormal behaviour or level of consciousness". This model achieved an AUC = 0.80 (CI 95%, 0.78-0.82).

    Conclusions: The results suggest that six specific variables were predictive of 7- and 30-day mortality with good accuracy which suggests that these symptoms, observations and mode of arrival may be important components to include along with vital signs in a future prediction tool of mortality among septic patients presenting to the ED. In addition, the Random Forests appears to be a suitable machine learning method on which to build future studies.

  • 3081.
    Karlsson Bok, Michelle
    Örebro University, School of Medical Sciences.
    A comparative study of methylphenidate and lisdexamphetamine in adult ADHD – a systematic literature review2021Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Attention deficit hyperactivity disorder (ADHD) affects not only children as it was initially assumed but continues into adulthood in 50% of the cases. ADHD is a major cause of cognitive disability in children, increases risks for criminal behavior, unemployment and is generally associated with low quality of life. The treatment of ADHD is primarily with the so-called central stimulants, which increase norepinephrine and dopamine transmission in the brain. These medications are classed as narcotics, and currently there are no clinically available predictors of efficacy, so trial and error attempts are made until one finds optimal treatment. During the trial time, risk for additional suffering and adverse events increase. The main aim of the study was to compare methylphenidate (MPH) and lisdexamphetamine (LDX) in the treatment of adult ADHD. A second aim was to investigate predictors for treatment outcome that can be used for precision medicine. This study was a systematic review of the existing litterateur by searching two databases, PubMed and Cochrane Library. Inclusion criteria were adults with ADHD, treated with MPH or LDX for at least 6 weeks, in a randomized placebo-controlled design. The results indicate that both LDX and MPH are highly effective, with similar efficacy, but that LDX may be associated with less adverse events in adults and hence a better choice. Possible predictors of treatment response found were severity of illness, dosage of drug and level of education. These findings, including major weaknesses and limitations, will be discussed in what follows.

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  • 3082.
    Karlsson, Christian
    Örebro University, School of Medical Sciences.
    The performance of two methods for subtyping of extended spectrum beta lactamase producing Escherichia coli.2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 3083.
    Karlsson, Daniel
    Örebro University, School of Medical Sciences.
    Anti-platelet effects of novel purine analogue MK1772021Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 3084.
    Karlsson, Elin
    Örebro University, School of Medical Sciences.
    Effekten på HbA1c efter ett års användning av FGM hos patienter med typ 1-diabetes2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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  • 3085.
    Karlsson, Elin
    Örebro University, School of Medical Sciences.
    Investigation and treatment after an osteoporotic fracture:: A survey of the Fracture Liaison Service in Örebro County2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: An osteoporotic fracture affects every other woman and every fourth man in Sweden. To meet the needs, Örebro County implemented in 2007 a fracture liaison service(FLS) to identify, investigate and treat these patients.

    Aim: To evaluate the efficacy of the FLS in Örebro County by reporting the prevalence ofbone mineral density testing and anti-osteoporotic treatment initiation following a low traumafracture. Secondary aim was to evaluate adherence to treatment after 12 months.

    Methods: 1269 medical records were retrospectively examined for all patients, 50-85 yearsold, with a fractured wrist, upper arm, hip, pelvis or vertebra in Örebro County in 2016.Patient characteristics and continuation through the FLS was studied. Primary objectives wereall descriptive, but various subgroups were compared using chi-square and independent ttests.Limit of significance at p<0.05.

    Results: 738 patients were eligible for inclusion (mean age 71.00 (±9.16) years, 76.6%women). 391 (53.0%) were referred for investigation, of which 348 (89.0%) attended. 253(72.7%) of the measured patients had indication for treatment, later prescribed to 76.7% ofthese, mainly once weekly oral bisphosphonates (64.4%). Adherence after 12 months wasavailable for 176 patients, of which 119 (67.6%) were still persistent.

    Conclusion: The FLS in Örebro County seems to be in line with national and internationalcounterparts. Still, there is room for improvement. The major gap appears to be identificationand referral for investigation of patients at risk of osteoporosis. Once passed the identificationstep, the losses through the program are in much smaller proportions.

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  • 3086.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, ÖRebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Sweden.
    Manchaiah, Vinaya
    Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine, Aurora; UCHealth Hearing and Balance, University of Colorado Hospital, Aurora, USA; Virtual Hearing Lab, Aurora, CO, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, South Africa; Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, India.
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Granberg, Sarah
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Gustafsson, Johanna
    Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Sweden; Faculty of Medicine and Health, School of Health Sciences, Örebro University, Sweden; Centre for the Study of Professions, Oslo Metropolitan University, Norway.
    Dahlström, Örjan
    Department of Behavioral Sciences and Learning, Linköping University, Sweden; Swedish Institute of Disability Research (SIDR), Linköping University, Sweden.
    Widén, Stephen
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hearing and Functioning in Everyday Life Questionnaire: Psychometric Evaluation and Revision2024In: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of the current study was to explore the construct validity and internal consistency reliability of the International Classification of Functioning, Disability and Health (ICF)-based original English version of the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) and to revise the HFEQ based on the results.

    METHOD: This study used a cross-sectional survey design. The data were collected using an online survey. Adults with self-reported hearing disability (n = 513) from the United States were included. The ICF components of body functions, activity and participation, and environmental factors were tested as the underlying structure of the HFEQ using confirmatory factor analysis and then adjusted by triangulation with previous content validation.

    RESULTS: The results of the current study confirmed the ICF components of body functions, activity and participation, and environmental factors as underlying constructs of the HFEQ. However, after triangulation with previous content validation, fine adjustments were made. The revised version of the HFEQ includes two removed items and a fine-tuned factor structure.

    CONCLUSION: The results confirm that the structure of the HFEQ aligns with the ICF, and the overall results indicate that HFEQ has acceptable construct validity and internal consistency.

  • 3087.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro Sweden .
    Manchaiah, Vinaya
    Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA; UCHealth Hearing and Balance, University of Colorado Hospital, Aurora, Colorado, USA; Virtual Hearing Lab, Collaborative initiative between University of Colorado School of Medicine and University of Pretoria, Aurora, Colorado, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, South Africa; Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India .
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Audiological Research Centre.
    Granberg, Sarah
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Gustafsson, Johanna
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Widén, Stephen
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Hearing and Functioning in Everyday Life Questionnaire (HFEQ): Construct validity, internal consistency reliability and floor and ceiling effectsManuscript (preprint) (Other academic)
  • 3088.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Granberg, Sarah
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Widén, Stephen
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Manchaiah, Vinaya
    Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA; UCHealth Hearing and Balance, University of Colorado Hospital, Aurora, Colorado, USA; Virtual Hearing Lab, Collaborative Initiative Between University of Colorado School of Medicine and University of Pretoria, Aurora, Colorado, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa; Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
    Swarnalatha Nagaraj, Vinay
    Audiology Group, Institute of Neuromedicine and Movement Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
    Pichora-Fuller, Kathleen M.
    Department of Psychology, University of Toronto, Mississauga, Ontario, Canada.
    Selb, Melissa
    ICF Research Branch and Swiss Paraplegic Research, Nottwil, Switzerland.
    Swanepoel, De Wet
    Virtual Hearing Lab, Collaborative Initiative Between University of Colorado School of Medicine and University of Pretoria, Aurora, Colorado, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Yerraguntla, Krishna
    Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
    Gustafsson, Johanna
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hearing and Functioning in Everyday Life Questionnaire: Development and Validation of an ICF-Based Instrument2023In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 44, no 6, p. 1498-1506Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Self-assessment instruments are commonly used in audiological rehabilitation. However, several studies highlight the lack of multidimensionality in existing outcome measures, with the consequence that they only partially capture aspects of functioning in everyday life for people living with hearing loss. This study aimed to develop and investigate the content validity of a self-assessment instrument based on the validated Brief International Classification of Functioning, Disability, and Health Core Set for Hearing Loss.

    DESIGN: The design was a two-part instrument development study. The first part focused on the item-generation process of the instrument, named the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) during an experts' workshop. The second part focused on international content validation of the instrument using group interviews. Strategic sampling was used and 30 adults with hearing loss from India, South Africa, and the United States participated in the group interviews.

    RESULTS: The expert's workshop resulted in the first version of the HFEQ containing 30 items. The results from group interviews show that the content of the HFEQ was considered to be valid concerning its relevance, comprehensiveness, and comprehensibility. A majority (73%) of the HFEQ items were perceived by the participants as relevant and easy to comprehend. For the remaining 27% of the items, the content was perceived to be relevant in all countries, but some terms and expressions were reported to require rewording or clearer examples. These modifications will be made in the next step of the development process.

    CONCLUSION: Content validation of the HFEQ demonstrates promising results, with participants perceiving the content as relevant and comprehensible. Further psychometric validation is required to investigate other psychometric properties, such as construct validity and reliability. The HFEQ has the potential to become a valuable new instrument for assessing everyday functioning in people with hearing loss in audiological rehabilitation and in research.

  • 3089.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro Sweden.
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Audiological Research Centre.
    Granberg, Sarah
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Widén, Stephen
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Manchaiah, Vinaya
    Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA; UCHealth Hearing and Balance, University of Colorado Hospital, Aurora, Colorado, USA; Virtual Hearing Lab, Collaborative initiative between University of Colorado School of Medicine and University of Pretoria, Aurora, Colorado, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, South Africa; Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India .
    Vinay, M.
    Audiology Group, Institute of Neuromedicine and Movement Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
    Pichora-Fuller, Kathleen
    Department of Psychology, University of Toronto, Mississauga, Ontario, Canada .
    Selb, Melissa
    ICF Research Branch and Swiss Paraplegic Research, Nottwil, Switzerland .
    Swanepoel, De Wet
    Virtual Hearing Lab, Collaborative initiative between University of Colorado School of Medicine and University of Pretoria, Aurora, Colorado, USA; Department of Speech-Language Pathology and Audiology, University of Pretoria, South Africa.
    Yerraguntla, Krishna
    Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
    Gustafsson, Johanna
    Örebro University, School of Health Sciences. Audiological Research Centre.
    Hearing and Functioning in Everyday Life Questionnaire (HFEQ): Development and Validation of an ICF-based InstrumentManuscript (preprint) (Other academic)
  • 3090.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Faculty of Medicine and Health, Audiological Research Centre, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Audiological Research Centre, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Widén, Stephen
    Örebro University, School of Health Sciences. Faculty of Medicine and Health, Audiological Research Centre, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Gustafsson, Johanna
    Örebro University, School of Health Sciences. Faculty of Medicine and Health, Audiological Research Centre, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Manchaiah, Vinaya
    Department of Speech and Hearing Sciences, Lamar University, Beaumont, TX, USA.
    Mahomed-Asmail, Faheema
    Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Swanepoel, De Wet
    Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Yerraguntla, Krishna
    Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
    Granberg, Sarah
    Örebro University, School of Health Sciences. Faculty of Medicine and Health, Audiological Research Centre, Örebro University, Örebro, Sweden; Swedish Institute of Disability Research (SIDR), Örebro University, Örebro, Sweden.
    Validation of the Brief International Classification of Functioning, Disability and Health (ICF) core set for hearing loss: an international multicentre study2021In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 60, no 6, p. 412-420Article in journal (Refereed)
    Abstract [en]

    Objective: Hearing loss (HL) affects the everyday functioning of millions of people worldwide. The Brief International Classification of Functioning Disability and Health (ICF) core sets for HL was developed to meet the complex health care needs of adults with HL. Because the brief core set for HL has not yet been validated internationally, this study aimed to investigate its validity from an international perspective.

    Design: A cross-sectional validation study based on data from structured interviews with adults with HL.

    Study sample: Participants (n = 571) from India, South Africa, Sweden and the US were included.

    Results: A six-factor solution explained 71% of the variance, focussing on issues related to communication, the social environment, participation in society, health care services, support, relationships and emotions (α = 0.915). Three ICF categories demonstrated low reliability - temperament and personality functions, seeing functions and school education.

    Conclusion: The Brief ICF core set for HL is valid for adults with HL internationally. However, to further increase its international validity, we recommend adding the categories d920 recreation and leisure and replacing d850 school education with the more inclusive block, d810-d839 education.

  • 3091.
    Karlsson, Elin
    et al.
    Örebro University, School of Health Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mäki-Torkko, Elina
    Örebro University, School of Medical Sciences. Audiological Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Widén, Stephen
    Örebro University, School of Health Sciences.
    Gustafsson, Johanna
    Örebro University, School of Health Sciences.
    Manchaiah, Vinaya
    Department of Speech and Hearing Sciences, Lamar University, Beaumont, TX, USA.
    Mahomed-Asmail, Faheema
    Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Yerraguntla, Krishna
    Department of Speech and Hearing, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
    Granberg, Sarah
    Örebro University, School of Health Sciences.
    Validation of the Brief (ICF) core set for hearing loss2021Conference paper (Other academic)
  • 3092.
    Karlsson, Emil
    Örebro University, School of Medical Sciences.
    Samband mellan symptom och fynd vid gastroskopi2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 3093.
    Karlsson, Emma
    Örebro University, School of Medical Sciences.
    A comparison of distal radius fractures treatedwith volar plate or combined plating2020Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 3094.
    Karlsson, Emma
    Örebro University, School of Medical Sciences.
    Konkordans mellan paratyroideascintigrafi och operationsfynd vid paratyroideaadenom2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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  • 3095.
    Karlsson, Emma
    et al.
    Department of Hand Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wretenberg, Per
    Örebro University, School of Medical Sciences. Department of Orthopedic Surgery.
    Björling, Patrik
    Department of Hand Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sagerfors, Marcus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Hand Surgery.
    Combined volar and dorsal plating vs. volar plating of distal radius fractures: A single-center study of 105 cases2020In: Hand surgery & rehabilitation, ISSN 2468-1229, Vol. 39, no 6, p. 516-521Article in journal (Refereed)
    Abstract [en]

    Despite recent advances in the surgical management of distal radius fractures (DRFs), the optimal treatment remains controversial as different fixation methods often have similar clinical functional and radiographic outcomes. The objective of this study was to assess the differences in outcomes 1 year postoperatively between volar plating and combined plating for DRFs. In a retrospective cohort study, we evaluated 105 consecutive patients operated with either a volar locking plate or combined dorsal and volar plating. The primary outcome was wrist range of motion (ROM). Secondary outcome measures included hand grip strength, visual analog scale (VAS) pain scores, radiographic examination and patient-related outcome measures. Patients treated with combined plating had significantly inferior wrist flexion, extension and ulnar deviation. The radiographic Batra score 1 year postoperatively was similar for both groups. The PRWE (patient-rated wrist evaluation) score was 16 for the volar plating group and 14 for the combined plating group. The QuickDASH (Quick disabilities of the hand arm and shoulder) score was 9 for the volar plating group and 16 for the combined plating group. VAS pain scores were 0 at rest and 2 during activity for both groups. Grip strength was similar between the two groups. Hardware removal was done in 18/78 patients for the combined plating group and 1/27 for the volar plate group. Two patients operated with combined plating had tendon ruptures. Our findings indicate that both methods can yield satisfactory clinical and radiographic outcomes. However, combined plating resulted in inferior wrist ROM and substantially higher frequency of hardware removal. The potential advantages of combined plating in stabilizing a comminuted DRF must be balanced by the potential drawbacks such as inferior wrist ROM and higher frequency of hardware removal.

  • 3096.
    Karlsson Good, Magnus
    et al.
    Örebro University, School of Medical Sciences. Department of Psychiatry, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kaldo, Viktor
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Department of Psychology, Faculty of Health and Life Sciences, Linnaeus University, Växjö, Sweden.
    Lundberg, Linnea
    Region Örebro County, Örebro, Sweden.
    Anthony, Susanne A.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Holländare, Fredrik
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Psychiatry.
    Increasing the accessibility to internet-based cognitive behavioural therapy fordepression: A single-blind randomised controlled trial of condensed versus full-textversionsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Research shows that internet-based cognitive behavioural therapy (iCBT) is aneffective treatment for depression. However, little is known about how the length of the text material in iCBT affects outcomes. The therapy might be more accessible if the text burden is reduced, especially for patients with ADHD symptoms and lower reading speed.

    Objective: The aim of this study was to test the hypothesis that a condensed version would be non-inferior to the existing full-text version. We further hypothesized that the condensed version would have better outcomes for participants with a low reading speed and more ADHD symptoms.

    Method: A single-blind randomized controlled trial was conducted (N = 267) comparing two versions of guided iCBT for depression; full-text (around 60 000 words) and condensed (around 30 000 words, with the option to listen to the text). Estimated between-group effect sizes and their confidence intervals were compared to a pre-determined non-inferiority margin (ES = 0.4). Moderation analyses of reading speed and ADHD symptoms were conducted, as well as comparisons of treatment engagement and knowledge acquisition.

    Results: The condensed version of iCBT was non-inferior to the full-text version on post treatment measures for depressive symptoms, anxiety symptoms, and quality of life. Non inferiority was inconclusive for depressive symptoms at the one-year follow-up. There was no significant moderation effects of reading speed or ADHD symptoms. However, there were significant two-way interactions in the condensed version. No significant differences between the two versions were found on measures of treatment engagement or knowledge acquisition.

    Conclusion: A condensed version of iCBT for depression can be used with non-inferiorresults. Due to unequal dropout rates between the groups, these results are preliminary and need to be replicated. 

  • 3097.
    Karlsson Good, Magnus
    et al.
    Örebro University, School of Medical Sciences. Department of Psychiatry, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kaldo, Viktor
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Department of Psychology, Faculty of Health and Life Sciences, Linnaeus University, Växjö, Sweden.
    Lundberg, Linnea
    Region Örebro County, Örebro, Sweden.
    Kraepelien, Martin
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Anthony, Susanne A.
    Department of Pediatrics, Skåne University Hospital, Region Skåne, Malmö, Sweden.
    Holländare, Fredrik
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Psychiatry.
    Increasing the accessibility to internet-based cognitive behavioural therapy for depression: A single-blind randomized controlled trial of condensed versus full-text versions2023In: Internet Interventions, ISSN 2214-7829, Vol. 34, article id 100678Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Research shows that internet-based cognitive behavioural therapy (iCBT) is an effective treatment for depression. However, little is known about how the length of the text material in iCBT affects outcomes.

    OBJECTIVE: The aim of this study was to test whether a condensed iCBT version for depression would be non-inferior to the existing full-text version in reducing depressive symptoms at post-treatment. We also wanted to test non-inferiority for secondary outcomes and explore reading speed and ADHD symptoms as potential moderators.

    METHOD: A single-blind randomized controlled trial was conducted (N = 267) comparing two versions of guided iCBT for depression; full-text (around 60,000 words) and condensed (around 30,000 words, with the option to listen to the text). Estimated between-group effect sizes and their confidence intervals for depression, anxiety and quality of life, were compared to a pre-determined non-inferiority margin (ES = 0.4). Moderation analyses of reading speed and ADHD symptoms were conducted.

    RESULTS: The condensed version of iCBT was non-inferior to the full-text version on post-treatment measures for depressive symptoms (95 % CI = -0.42-0.24), anxiety symptoms (95 % CI = -0.24-0.32), and quality of life (95 % CI = -0.09-0.49). Non-inferiority was inconclusive for depressive symptoms at the one-year follow-up (95 % CI = -0.60-0.47). There was no significant moderation effects of reading speed (p = 0.06) or ADHD symptoms (p = 0.11) on depressive symptoms.

    CONCLUSION: These results indicate that a condensed version of iCBT for depression is as effective at treating depression as the full-text version. By shortening texts, iCBT may be made available to more people. Due to unequal dropout rates between the groups, these results are preliminary and need to be replicated.

  • 3098.
    Karlsson, Jakob
    et al.
    Applied Chemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Lopez-Sanchez, Patricia
    Food Technology, Department of Analytical Chemistry, Nutrition and Food Science, University of Santiago de Compostela, Campus Terra, Spain.
    Marques, Tatiana Milena
    Örebro University, School of Medical Sciences.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Castro Alves, Victor
    Örebro University, School of Science and Technology.
    Krona, Annika
    RISE Research Institutes of Sweden, Agriculture and Food, Gothenburg, Sweden.
    Ström, Anna
    Applied Chemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Effect of heating of pea fibres on their swelling, rheological properties and in vitro colon fermentation2024In: Food Hydrocolloids, ISSN 0268-005X, E-ISSN 1873-7137, Vol. 147, article id 109306Article in journal (Refereed)
    Abstract [en]

    Dietary fibre intake is essential for all human beings and has been correlated to beneficial health effects. Pea hull fibres (PF) are generally seen as a side stream during extraction of protein and starch from yellow pea but could be used in various food products to boost fibre content. In this study, the thermal treatment of pea hull fibres was investigated in terms of physicochemical properties and in vitro colonic fermentation. The PF that was subjected to heating showed an increase of fibres solubilised in the liquid and particle size. Results also showed that viscosity and storage modulus increased with thermal treatment, possibly due to the swelling of the PF. The pea fibre was readily fermentable based on total gas production and pH. However, the susceptibility to fermentation of PF did not increase with thermal treatment. Total gas production and short chain fatty acid produced were similar independent of thermal treatment. Conclusively, heating of the PF resulted in increased ability to structure water suspension, owing to increased fibre particle size, but is not sufficient to increase short chain fatty acid production during colonic fermentation. To explain this, we propose that the changes in cell wall structure were not major enough to induce higher fermentability.

  • 3099.
    Karlsson, Jakob
    et al.
    Applied Chemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Lopez-Sanchez, Patricia
    Food Technology, Department of Analytical Chemistry, Nutrition and Food Science, University of Santiago de Compostela, Facultad de Ciencias, Campus Terra, Spain.
    Marques, Tatiana Milena
    Örebro University, School of Medical Sciences.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Castro Alves, Victor
    Örebro University, School of Science and Technology.
    Krona, Annika
    RISE Research Institutes of Sweden, Agriculture and Food, Gothenburg, Sweden.
    Ström, Anna
    Applied Chemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Physico-chemical properties of pea fibre and pea protein blends and the implications for in vitro batch fermentation using human inoculum2024In: Food Hydrocolloids, ISSN 0268-005X, E-ISSN 1873-7137, Vol. 150, article id 109732Article in journal (Refereed)
    Abstract [en]

    The incorporation of fibre into pea protein matrices influences their microstructure, yet our understanding of their gut fermentability remains unexplored. In this study, dietary fibres and protein from yellow pea were investigated for their physico-chemical properties and impact on in vitro colonic fermentation using human inoculum. Pea fibre and pea protein blends were studied at different pH and after thermal treatment at 95 ◦C for 30 min with oscillatory rheology, static light scattering and confocal laser scanning microscopy. The effect on in vitro colonic fermentation was evaluated measuring gas production, ammonia, and short chain fatty acid (SCFA) production. Rheology indicated that during thermal treatment a firmer gel is formed close to the protein isoelectric point with a structure characterised by aggregation, but less particle swelling compared to other pH. Addition of fibre led to higher storage modulus (G′), with the fibre dominating the rheological properties. Fermentation of samples containing protein led to higher levels of ammonia and SCFA compared to only fibres. Blends produced higher amounts of valerate, i-valerate and caproate, and lower amounts of ammonia. Reduced fermentation of proteins in the presence of fibres was also reflected in a more intact microstructure of the protein particles in the digesta. Although thermal treatment of blends caused particle swelling and induced gelation, only small differences could be discerned in the in vitro colonic fermentation outcomes. Our results highlight that potentially harmful fermentation products from protein, such as ammonia, were reduced in the presence of pea hull fibre.

  • 3100.
    Karlsson, Jan
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Center.
    Galavazi, Marije
    Örebro University, School of Medical Sciences.
    Jansson, Stefan P. O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Center.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Effects on body weight, eating behavior, and quality of life of a low-energy diet combined with behavioral group treatment of persons with class II or III obesity: A 2-year pilot study2021In: Obesity Science & Practice, E-ISSN 2055-2238, Vol. 7, no 1, p. 4-13Article in journal (Refereed)
    Abstract [en]

    Objective: Obesity is associated with reduced health-related quality of life (HRQoL). Outcomes of nonsurgical weight loss treatment on HRQoL are inconsistent and it is unclear how much weight reduction, or what type of treatment, is required for significant improvements. This study aimed to evaluate the effects of a lifestyle intervention program on weight, eating behaviors, and HRQoL, and to describe participants' experiences of treatment.

    Methods: This 2-year intervention trial in persons with class II or III obesity comprised a 3-month liquid low-energy diet (880 kcal/d) followed by a 3-month reintroduction to regular foods, combined with behavioral group treatment.

    Results: Fifty-five participants (73% women) were included, mean (SD) age 43.2 (12.4) years, and mean body mass index 42.0 (6.0) kg/m(2). Mean weight loss at 6, 12, and 24 months was 18.9%, 13.7%, and 7.2%, respectively. Short- and long-term effects on eating behavior were favorable. Twelve of 14 HRQoL domains were improved at 6 months, compared to eight domains at 12 months. After 24 months, 2 of 14 domains, physical and psychosocial functioning, were improved. The treatment program was well accepted by the participants.

    Conclusions: Substantial weight loss after 6 months was associated with extensive improvements in HRQoL, comprising the physical, psychosocial, and mental domains. Significant weight regain was observed between 6 and 24 months follow-up. Modest weight loss after 24 months was associated with moderate improvement in physical functioning and large improvement in psychosocial functioning. The effect on psychosocial functioning is most likely related to both weight loss and behavioral treatment.

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