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  • 1.
    Coomans, Marijke B.
    et al.
    Leiden Univ, Netherlands.
    Dirven, Linda
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Aaronson, Neil K.
    Netherlands Canc Inst, Netherlands.
    Baumert, Brigitta G.
    Univ Hosp Bonn, Germany; Maastricht Univ, Netherlands; Maastricht Univ, Netherlands.
    Van Den Bent, Martin
    Erasmus MC Canc Inst, Netherlands.
    Bottomley, Andrew
    European Org Res Treatment Canc, Belgium.
    Brandes, Alba A.
    Azienda USL IRCCS, Italy.
    Chinot, Olivier
    Aix Marseille Univ, France.
    Coens, Corneel
    European Org Res Treatment Canc, Belgium.
    Gorlia, Thierry
    European Org Res and Treatment Canc Headquarters, Belgium.
    Herrlinger, Ulrich
    Univ Bonn, Germany.
    Keime-Guibert, Florence
    Pitie Salpetriere Hosp Grp, France.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Martinelli, Francesca
    European Org Res Treatment Canc, Belgium.
    Stupp, Roger
    Northwestern Univ, IL 60611 USA.
    Talacchi, Andrea
    San Giovanni Addolorata Hosp, Italy.
    Weller, Michael
    Univ Hosp, Switzerland; Univ Zurich, Switzerland.
    Wick, Wolfgang
    Univ Hosp Heidelberg, Germany; Univ Hosp Heidelberg, Germany; German Canc Res Ctr, Germany.
    Reijneveld, Jaap C.
    Univ Amsterdam, Netherlands.
    Taphoorn, Martin J. B.
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?2019In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 21, no 11, p. 1447-1457Article in journal (Refereed)
    Abstract [en]

    Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (amp;gt;= 10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P amp;lt; 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P amp;lt; 0.001), independent of other factors. Conclusions. Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients functioning as measured with a self-report questionnaire.

  • 2.
    Coomans, Marijke
    et al.
    Leiden Univ, Netherlands.
    Dirven, Linda
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Aaronson, Neil K.
    Netherlands Canc Inst, Netherlands.
    Baumert, Brigitta G.
    Univ Hosp Bonn, Germany; Maastricht Univ, Netherlands; Maastricht Univ, Netherlands.
    van den Bent, Martin
    Erasmus MC Canc Inst, Netherlands.
    Bottomley, Andrew
    European Org Res Treatment Canc, Belgium.
    Brandes, Alba A.
    Azienda USL IRCCS Inst Neurol Sci, Italy.
    Chinot, Olivier
    Aix Marseille Univ, France.
    Coens, Corneel
    European Org Res and Treatment Canc Headquarters, Belgium.
    Gorlia, Thierry
    Univ Bonn, Germany; Univ Bonn, Germany.
    Herrlinger, Ulrich
    Grp Hop Pitie Salpetriere, France.
    Keime-Guibert, Florence
    Groupe Hôpital Pitié-Salpetrière, Paris, France.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Martinelli, Francesca
    Northwestern Univ, IL 60611 USA.
    Stupp, Roger
    Azienda Osped San Giovanni Addolorata, Italy.
    Talacchi, Andrea
    Univ Hosp, Switzerland; Univ Zurich, Switzerland.
    Weller, Michael
    Univ Hosp Heidelberg, Germany; German Consortium Translat Canc Res DKTK, Germany.
    Wick, Wolfgang
    Univ Amsterdam, Netherlands.
    Reijneveld, Jaap C.
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Taphoorn, Martin J. B.
    Leiden University Medical Center, Leiden, Netherlands; Haaglanden Medical Center, Den Haag, Netherlands.
    The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials2019In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 190-198Article in journal (Refereed)
    Abstract [en]

    Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.

  • 3.
    Dahlrot, R. H.
    et al.
    Odense Univ Hosp, Denmark.
    Dowsett, J.
    Odense Univ Hosp, Denmark.
    Fosmark, S.
    Odense Univ Hosp, Denmark.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Henriksson, R.
    Umea Univ, Sweden; Reg Canc Ctr Stockholm Gotland, Sweden.
    Boldt, H.
    Odense Univ Hosp, Denmark.
    de Stricker, K.
    Odense Univ Hosp, Denmark.
    Sorensen, M. D.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Poulsen, H. S.
    Rigshosp, Denmark.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Hansen, S.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Kristensen, B. W.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis2018In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, no 2, p. 172-184Article in journal (Refereed)
    Abstract [en]

    Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. Results: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

  • 4.
    Erichsén, Eva
    et al.
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Friedrichsen, Maria
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Constipation in specialized palliative care: prevalence, definition and patient perceived symptom distress2015In: Journal of Palliative Medicine, ISSN 1096-6218, E-ISSN 1557-7740, Vol. 18, no 7, p. 585-592Article in journal (Refereed)
    Abstract [en]

    Context: The prevalence of constipation among patients in palliative care has varied in prior research, from 18-90 %, depending on different study factors.

    Objectives: The aim of this study was to describe and explore the prevalence and symptom distress of constipation, using different definitions of constipation, in patients admitted to specialized palliative care settings.

    Methods: Data was collected in a cross-sectional survey from 485 patients in 38 palliative care units in Sweden. Variables were analyzed using logistic regression and summarized as odds ratio (OR).

    Result: The prevalence of constipation varied between 7 – 43 %, depending on the definition used. Two constipation- groups were found: (i) Medical constipation- group (MCG; ≤ 3 defecations/week n=114; 23%); (ii) Perceived constipation- group (PCG; Patients with a perception of being constipated the last two weeks; n= 171; 35%). Three sub-groups emerged: patients with (a) only medical constipation (7 %), (b) only perceived constipation (19 %), and (c) with both medical and perceived constipation (16%). There were no differences in symptom severity between groups; 71% of all constipated patients had severe constipation.

    Conclusion: The prevalence of constipation may differ, depending on the definition used and how constipation is assessed. In this study we found two main groups and three sub-groups, analyzed from the definitions of frequency of bowel movements and experience of being constipated. To be able to identify constipation, the patients’ definition has to be further explored and assessed.

  • 5.
    Heedman, Per-Anders
    et al.
    Region Östergötland, Local Health Care Services in Central Östergötland. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Åstradsson, E.
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Blomquist, K.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Palliation of Malignant Biliary Obstruction: Adverse Events are Common after Percutaneous Transhepatic Biliary Drainage2018In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 107, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Endoscopic stents in the common bile duct is the first treatment choice to alleviate symptoms of biliary obstruction due to malignant disease. When endoscopic stenting fails in palliative patients, one option is to use a percutaneous transhepatic biliary drainage, but it is not clear whether and how it can reduce the symptom load. The aim of this study was to evaluate benefits and disadvantages of percutaneous transhepatic biliary drainage in palliative care. Material and Methods: Inclusion criteria were malignant disease and bilirubin 26 mu mol/L in plasma. A structured protocol for obtaining data from the medical records was used. Data were collected from the time of last computed tomography scan before the percutaneous transhepatic biliary drainage was placed and during 14days afterward. Results and Conclusion: Inclusion criteria were fulfilled in 140 patients. Median age was 70years (33-91years). Some 126 patients had a remaining external percutaneous transhepatic biliary drainage. Jaundice was the initial symptom in 62 patients (44%). Within the first week after percutaneous transhepatic biliary drainage, the bilirubin decreased from 237 mu mol/L (31-634) to 180 mu mol/L (17-545). Only 25% reached a level below the double upper reference value. Pruritus occurred in 27% before the percutaneous transhepatic biliary drainage, but the bilirubin value did not differ from patients without pruritus. However, the pruritus was relieved in 56% with percutaneous transhepatic biliary drainage. Antibiotic prophylaxis protected to some extent from infectious complications. Adverse events were common and early mortality was high (16% within 14days). Jaundice should not by itself be an indication for percutaneous transhepatic biliary drainage for palliation except when the aim is to prepare the patient for chemotherapy. It is mandatory that the patients are informed carefully about what can be expected regarding the positive effects and the risks of adverse events.

  • 6.
    Heenkenda, Menikae Kanchena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mudaisi, Munila
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bratthall, Charlotte
    Dist Hosp, Sweden.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Åkesson, Lisa
    Linköping University, Department of Thematic Studies. Linköping University, Faculty of Arts and Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Osman, Abdimajid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group2019In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 183, p. 136-142Article in journal (Refereed)
    Abstract [en]

    Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multi-forme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. Materials and methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. Results: In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. Conclusion: In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.

    The full text will be freely available from 2020-10-22 14:11
  • 7.
    Kastbom, Lisa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ljungsbro.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Karlsson, Marit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    A good death from the perspective of palliative cancer patients2017In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 25, no 3, p. 933-939Article in journal (Refereed)
    Abstract [en]

    Although previous research has indicated some recurrent themes and similarities between what patients from different cultures regard as a good death, the concept is complex and there is lack of studies from the Nordic countries. The aim of this study was to explore the perception of a good death in dying cancer patients in Sweden. Interviews were conducted with 66 adult patients with cancer in the palliative phase who were recruited from home care and hospital care. Interviews were analysed using qualitative content analysis. Participants viewed death as a process. A good death was associated with living with the prospect of imminent death, preparing for death and dying comfortably, e.g., dying quickly, with independence, with minimised suffering and with social relations intact. Some were comforted by their belief that death is predetermined. Others felt uneasy as they considered death an end to existence. Past experiences of the death of others influenced participants views of a good death. Healthcare staff caring for palliative patients should consider asking them to describe what they consider a good death in order to identify goals for care. Exploring patients personal experience of death and dying can help address their fears as death approaches.

  • 8.
    Kastbom, Lisa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ljungsbro.
    Milberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Advanced Home Care in Norrköping.
    Karlsson, Marit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    We have no crystal ball-advance care planning at nursing homes from the perspective of nurses and physicians2019In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate clinicians perspectives on the factors that shape the process of advance care planning in a nursing home context. Design: Interviews. Latent qualitative content analysis. Setting: Nine nursing homes in Sweden. Subjects: 14 physicians and 11 nurses working at nursing homes. Main outcome measures: Participants views on advance care planning (ACP) at nursing homes. Results: The analysis of the interviews resulted in four manifest categories: Exploration of preferences and views, e.g. exploring patient wishes regarding end-of-life issues and restrictions in care at an early stage, and sensitivity to patients readiness to discuss end-of-life issues; Integration of preferences and views, e.g. integration of patients preferences and staffs and family members views; Decision amp; documentation of the ACP, e.g. clear documentation in patients medical records that are up-to-date and available for staff caring for the patient, and Implementation amp; re-evaluation of the ACP, e.g. nurse following up after ACP-appointment to confirm the content of the documented ACP. The latent theme, Establishing beneficence - defending oneself against tacit accusations of maleficence, emerged as a deeper meaning of all the four (manifest) parts of the ACP-process Conclusion: This study stresses the importance of involving patients, family members, and the team in the work with advance care planning in nursing homes. In addition, clear medical record documentation and proficiency in end-of-life communication related to advance care planning for physicians as well as nurses may also be factors that significantly shape advance care planning in a nursing home context.

  • 9.
    Lind, Leili
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. SICS East Swedish ICT, Linköping, Sweden.
    Carlgren, Gunnar
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Karlsson, Daniel
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Old-and With Severe Heart Failure: Telemonitoring by Using Digital Pen Technology in Specialized Homecare: System Description, Implementation, and Early Results2016In: Computers, Informatics, Nursing, ISSN 1538-2931, E-ISSN 1538-9774, Vol. 34, no 8, p. 360-368Article in journal (Refereed)
    Abstract [en]

    Telehealth programs for heart failure have been studied using a variety of techniques. Because currently a majority of the elderly are nonusers of computers and Internet, we developed a home telehealth system based on digital pen technology. Fourteen patients (mean age, 84 years [median, 83 years]) with severe heart failure participated in a 13-month pilot study in specialized homecare. Participants communicated patient-reported outcome measures daily using the digital pen and health diary forms, submitting a total of 3 520 reports. The reports generated a total of 632 notifications when reports indicated worsening health. Healthcare professionals reviewed reports frequently, more than 4700 times throughout the study, and acted on the information provided. Patients answered questionnaires and were observed in their home environment when using the system. Results showed that the technology was accepted by participants: patients experienced an improved contact with clinicians; they felt more compliant with healthcare professionals advice, and they felt more secure and more involved in their own care. Via the system, the healthcare professionals detected heart failure-related deteriorations at an earlier stage, and as a consequence, none of the patients were admitted into hospital care during the study.

  • 10.
    Lind, Leili
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. SICS East Swedish ICT, Linköping, Sweden.
    Carlgren, Gunnar
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Mudra, Jacqueline
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Synnergren, Henrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hilding, Niclas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Karlsson, daniel
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Preliminary results of a telemonitoring study: COPD and heart failure patients exhibit great difference in their need of health care2015In: European Respiratory Journal: Official Scientific Journal of ERS / [ed] Marc Humbert, European Respiratory Society , 2015, Vol. 46/suppl 59, p. PA2790-PA2790Conference paper (Other academic)
    Abstract [en]

    Background: Growing populations of elderly patients with advanced stages of COPD or heart failure (HF) urge the need for specialized health care in the patients' home. A telemonitoring study has been initiated including patients using digital pens. Health care was provided by the specialized home care unit at a university hospital. Through an IT system the staff checked all daily patient reports. We hypothesized that the two groups of patients, advanced COPD or HF, would exhibit differences regarding exacerbations and the need of health care.

    Objective: To study exacerbations of COPD or HF, and patient health care consumption.

    Methods: A tele-monitoring system, the Health diary, which is based on digital pen technology, was employed. Exacerbations were identified using information provided through the telemonitoring system. Consumed health care was assessed as the number of patient contacts (home visits or telephone consultations).

    Results: Presently, 33 patients with advanced disease are enrolled (13 COPD and 20 HF patients) of which 11 patients (6 COPD and 5 HF patients) have completed the 1-yr study period or have died during the study period (2 COPD and 4 HF patients). Exacerbations were 2.8 and 0.8 and patient contacts were 96 and 42 per COPD and HF patient, respectively. While HF patients were significantly older than COPD patients, the two groups demonstrated no difference regarding gender distribution and comorbidity.

    Conclusions: COPD patients exhibit exacerbations more frequently and demand much more home health care than patients with HF do. It seems that this difference of health care consumption is mainly due to disease characteristics.

  • 11.
    Lind, Leili
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. RISE SICS East.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland.
    Carlgren, Gunnar
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Mudra, Jacqueline
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Synnergren, Henrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hilding, Niclas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland.
    Karlsson, Daniel
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Re-organising care of elderly, multi-morbid COPD and heartfailure patients with low digital literacy: —a 4 year Swedishtelehealth intervention study2016In: Health—exploring complexity: an interdisciplinary systems approach HEC2016 / [ed] Grill, E., Müller, M. & Mansmann, U., Munich, Germany, 2016, Vol. 31, p. 118-118Conference paper (Refereed)
  • 12.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Studies for Better Treatment of Patients with Glioma2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.

    The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.

    The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).

    The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.

    The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.

    In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.

    List of papers
    1. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Open this publication in new window or tab >>Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Show others...
    2012 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, no 9, p. 916-926Article in journal (Refereed) Published
    Abstract [en]

    Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84333 (URN)10.1016/S1470-2045(12)70265-6 (DOI)000308425600019 ()
    Note

    Funding Agencies|Merck||Lions Cancer Research Foundation||University of Umea||Swedish Cancer Society||Schering-Plough||University of Umea, Sweden||Cancer Fonden, Sweden||

    Available from: 2012-10-05 Created: 2012-10-05 Last updated: 2019-11-06
    2. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Open this publication in new window or tab >>Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Show others...
    2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 12, p. 1776-1785Article in journal (Refereed) Published
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2017
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-144005 (URN)10.1080/0284186X.2017.1332780 (DOI)000418118800016 ()28675067 (PubMedID)
    Note

    Funding Agencies|Merck; Linkoping University Hospital for Neuro-research; Lions Cancer Foundation; Cancer Foundation Norrland, Umea, Sweden; LIUCancer; South-East Sweden FORSS

    Available from: 2018-01-02 Created: 2018-01-02 Last updated: 2019-11-06
    3. Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Open this publication in new window or tab >>Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Show others...
    2019 (English)In: Neuro-Oncology Practice, ISSN 2054-2577, p. 1-9Article in journal (Refereed) Published
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Place, publisher, year, edition, pages
    Oxford: Oxford University Press, 2019
    National Category
    Medical Bioscience Clinical Laboratory Medicine
    Identifiers
    urn:nbn:se:liu:diva-160808 (URN)10.1093/nop/npz039 (DOI)
    Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-11-06Bibliographically approved
  • 13.
    Malmström, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Skovgaard Poulsen, Hans
    Rigshosp, Denmark.
    Henning Gronberg, Bjorn
    Norwegian University of Science and Technology, Norway; Trondheim Regional and University Hospital, Norway.
    Stragliotto, Giuseppe
    Karolinska University Hospital, Sweden.
    Hansen, Steinbjorn
    University of Southern Denmark, Denmark.
    Asklund, Thomas
    Karolinska University Hospital, Sweden; Umeå University, Sweden.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dowsett, Joseph
    University of Southern Denmark, Denmark.
    Winther Kristensen, Bjarne
    University of Southern Denmark, Denmark.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Henriksson, Roger
    Umeå University, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 12, p. 1776-1785Article in journal (Refereed)
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

  • 14.
    Mosrati, Mohamed Ali
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Krysztofiak, Adam
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Anna-Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bratthall, Charlotte
    Dist Hospital, Sweden.
    Strandeus, Michael
    Ryhov Hospital, Sweden.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 18, p. 16663-16673Article in journal (Refereed)
    Abstract [en]

    Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.

  • 15.
    Ring Jacobsson, Lisa
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences.
    Milberg, Anna
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hjelm, Katarina
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences.
    Friedrichsen, Maria
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Experiences, Own Management and Beliefs regarding Residual Symptoms among People with Coeliac DiseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: To explore experiences and beliefs concerning residual symptoms despite a gluten-free diet in women and men with coeliac disease, with a focus on causes and management.

    Background: Between 7% and 30% of people with coeliac disease suffer from residual symptoms, despite following a long-term gluten-free diet, and it has been proposed that women in particular, continue to experience such inconveniences. There is a lack of knowledge about own beliefs concerning the underlying causes of persistent symptoms among people with coeliac disease and their own management of these symptoms.

    Methods: A qualitative explorative design with semi-structured interviews with 22 adults, 11 females and 11 males, with coeliac disease in Sweden. Data were analyzed using qualitative content analysis.

    Results: The disease was continuing to have a substantial impact on the informants’ lives even after several years’ treatment. The interviews revealed residual symptoms of both a gastrointestinal and extra-intestinal nature, which were considered to influence their personality. The management of persistent symptoms resembled thorough detective work, and both efforts to find the missing puzzle piece and strategies to prevent problems were used. Beliefs about the underlying causes of these symptoms were bodily convictions and that it was impossible to live completely gluten-free.

    Conclusion: People with treated coeliac disease, irrespective of gender, may experience residual symptoms of both a physical and psychological nature, causing major negative impacts on their lives in different ways. In the light of this, healthcare staff should change their practices regarding the follow-up of these people, and in addition to medical care should  provide guidance on management strategies to facilitate the daily life of these people. Furthermore, information to people who have just been diagnosed should make them aware of the possibility that they may come to experience continued symptoms, despite treatment.

  • 16.
    Roodakker, Kenney R.
    et al.
    Uppsala University, Sweden.
    Elsir, Tamador
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Edqvist, Per-Henrik D.
    Uppsala University, Sweden.
    Hagerstrand, Daniel
    Karolinska Institute, Sweden.
    Carison, Joseph
    Karolinska Institute, Sweden.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Henriksson, Roger
    Umeå University, Sweden; Regional Cancer Centre, Sweden.
    Ponten, Fredrik
    Uppsala University, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stupp, Roger
    University of Zurich Hospital, Switzerland.
    Tchougounova, Elena
    Uppsala University, Sweden.
    Nister, Monica
    Karolinska Institute, Sweden.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Smits, Anja
    Uppsala University, Sweden; University of Gothenburg, Sweden.
    PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 45, p. 72431-72442Article in journal (Refereed)
    Abstract [en]

    PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing lowgrade tumors and harbor IDH mutations.

  • 17.
    van Thuijl, Hinke F.
    et al.
    University of Calif San Francisco, CA 94143 USA; Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    Mazor, Tali
    University of Calif San Francisco, CA 94143 USA.
    Johnson, Brett E.
    University of Calif San Francisco, CA 94143 USA.
    Fouse, Shaun D.
    University of Calif San Francisco, CA 94143 USA.
    Aihara, Koki
    University of Tokyo, Japan; University of Tokyo, Japan.
    Hong, Chibo
    University of Calif San Francisco, CA 94143 USA.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Heimans, Jan J.
    Vrije University of Amsterdam Medical Centre, Netherlands.
    Kloezeman, Jenneke J.
    Erasmus MC, Netherlands.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lamfers, Martine L. M.
    Erasmus MC, Netherlands.
    Saito, Nobuhito
    University of Tokyo, Japan.
    Aburatani, Hiroyuki
    University of Tokyo, Japan.
    Mukasa, Akitake
    University of Tokyo, Japan.
    Berger, Mitchell S.
    University of Calif San Francisco, CA 94143 USA.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Taylor, Barry S.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Molinaro, Annette M.
    University of Calif San Francisco, CA 94143 USA; University of Calif San Francisco, CA 94143 USA.
    Wesseling, Pieter
    Vrije University of Amsterdam Medical Centre, Netherlands; Radboud University of Nijmegen, Netherlands.
    Reijneveld, Jaap C.
    Vrije University of Amsterdam Medical Centre, Netherlands; University of Amsterdam, Netherlands.
    Chang, Susan M.
    University of Calif San Francisco, CA 94143 USA.
    Ylstra, Bauke
    Vrije University of Amsterdam Medical Centre, Netherlands.
    Costello, Joseph F.
    University of Calif San Francisco, CA 94143 USA.
    Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment2015In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, no 4, p. 597-607Article in journal (Refereed)
    Abstract [en]

    Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-na less than ve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.

  • 18.
    Wu, Wendy Yi-Ying
    et al.
    Umea Univ, Sweden.
    Johansson, Gunnar
    Umea Univ, Sweden.
    Wibom, Carl
    Umea Univ, Sweden.
    Brannstrom, Thomas
    Umea Univ, Sweden.
    Malmström, Annika
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Henriksson, Roger
    Umea Univ, Sweden.
    Golovleva, Irina
    Umea Univ, Sweden.
    Bondy, Melissa L.
    Stanford Univ, CA 94305 USA; Baylor Coll Med, TX 77030 USA.
    Andersson, Ulrika
    Umea Univ, Sweden.
    Dahlin, Anna M.
    Umea Univ, Sweden.
    Melin, Beatrice
    Umea Univ, Sweden.
    The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes2019In: CANCERS, Vol. 11, no 12, article id 2001Article, review/survey (Refereed)
    Abstract [en]

    Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

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