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  • 1.
    Abate Waktola, Ebba Abate
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. EPHI, Ethiopia.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Verma, Deepti
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Belayneh, Meseret
    Univ Addis Abeba, Ethiopia.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Stendahl, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Schön, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Kalmar County Hospital, Kalmar, Sweden.
    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 3126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.

  • 2.
    Abdelrahman, Islam
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Validation of the burn intervention score in a National Burn Centre2018Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, nr 5, s. 1159-1166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Linköping burn score has been used for two decades to calculate the cost to the hospital of each burned patient. Our aim was to validate the Burn Score in a dedicated Burn Centre by analysing the associations with burn-specific factors: percentage of total body surface area burned (TBSA%), cause of injury, patients referred from other (non-specialist) centres, and survival, to find out which of these factors resulted in higher scores. Our second aim was to analyse the variation in scores of each category of care (surveillance, respiration, circulation, wound care, mobilisation, laboratory tests, infusions, and operation).

    We made a retrospective analysis of all burned patients admitted during the period 2000–15. Multivariable regression models were used to analyse predictive factors for an increased daily burn score, the cumulative burn score (the sum of the daily burn scores for each patient) and the total burn score (total sum of burn scores for the whole group throughout the study period) in addition to sub-analysis of the different categories of care that make up the burn score.

    We retrieved 22 301 daily recordings for inpatients. Mobilisation and care of the wound accounted for more than half of the total burn score during the study. Increased TBSA% and age over 45 years were associated with increased cumulative (model R2 0.43, p < 0.001) and daily (model R2 0.61, p < 0.001) burn scores. Patients who died had higher daily burn scores, while the cumulative burn score decreased with shorter duration of hospital stay (p < 0.001).

    To our knowledge this is the first long term analysis and validation of a system for scoring burn interventions in patients with burns that explores its association with the factors important for outcome. Calculations of costs are based on the score, and it provides an indicator of the nurses’ workload. It also gives important information about the different dimensions of the care provided from thorough investigation of the scores for each category.

  • 3.
    Abdelrahman, Islam
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Olofsson, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Division of overall duration of stay into operative stay and postoperative stay improves the overall estimate as a measure of quality of outcome in burn care.2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 3, artikel-id e0174579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients and Methods: Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay.less thanbr /greater thanResults: Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, pless than0.01). The size of the burn, and the number of operations, were the independent factors that influenced operative stay (R2 0.65). Except for the size of the burn other factors were associated with duration of postoperative stay: wound related, psychological and other medical causes, advanced medical support, and accommodation arrangements before discharge, of which the two last were the most important with an increase of (mean) 12 and 17 days (pless than0.001, R2 0.51).less thanbr /greater thanConclusion: Adjusted operative stay showed less variation than total hospital stay and thus can be considered a more accurate outcome measure for surgically managed burns. The size of burn and number of operations are the factors affecting this outcome measure.

  • 4.
    Abdelrahman, Islam
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. a Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Improvement in mortality at a National Burn Centre since 2000: Was it the result of increased resources?2017Ingår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, nr 25, artikel-id e6727Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Abstract The aim of this study was to find out whether the charging costs (calculated using interventional burn score) increased as mortality decreased. During the last 2 decades, mortality has declined significantly in the Linköping Burn Centre. The burn score that we use has been validated as a measure of workload and is used to calculate the charging costs of each burned patient. We compared the charging costs and mortality in 2 time periods (2000–2007 and 2008–2015). A total of 1363 admissions were included. We investigated the change in the burn score, as a surrogate for total costs per patient. Multivariable regression was used to analyze risk-adjusted mortality and burn score. The median total body surface area % (TBSA%) was 6.5% (10–90 centile 1.0–31.0), age 33 years (1.3–72.2), duration of stay/ TBSA% was 1.4 days (0.3–5.3), and 960 (70%) were males. Crude mortality declined from 7.5% in 2000–2007 to 3.4% in 2008–2015, whereas the cumulative burn score was not increased (P=.08). Regression analysis showed that risk-adjusted mortality decreased (odds ratio 0.42, P=.02), whereas the adjusted burn score did not change (P=.14, model R2 0.86). Mortality decreased but there was no increase in the daily use of resources as measured by the interventional burn score. The data suggest that the improvements in quality obtained have been achieved within present routines for care of patients (multidisciplinary/ orientated to patients’ safety).

    Abbreviation: TBSA% = total body surface area %.

  • 5.
    Abdelrahman, Islam
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. The Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. The Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Use of the burn intervention score to calculate the charges of the care of burns2019Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, nr 2, s. 303-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care. Methods All patients admitted with burns during the period 2010–15 were included. We analysed clinical and economic data from the daily burn scores during the acute phase of the burn until discharge from the burn centre. Results Total median charge/patient was US$ 28 199 (10th–90th centiles 4668-197 781) for 696 patients admitted. Burns caused by hot objects and electricity resulted in the highest charges/TBSA%, while charges/day were similar for the different causes of injury. Flame burns resulted in the highest mean charges/admission, probably because they had the longest duration of stay. Mean charges/patient increased in a linear fashion among the different age groups. Conclusion Our intervention-based estimate of charges has proved to be a valid tool that is sensitive to the procedures that drive the costs of the care of burns such as large TBSA%, intensive care, and operations. The burn score system could be reproduced easily in other burn centres worldwide and facilitate the comparison regardless of the differences in the currency and the economic circumstances.

  • 6.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Böttcher, Malin Fagerås
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria C
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Oldaeus, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, nr 5, s. 1174-1180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants.

    OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri.

    METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens.

    RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected.

    CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.

  • 7.
    Abrahamsson, Thomas R
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Sinkiewicz, Gabriela
    Department of Biomedical Lab Science, Malmö University, Malmö, Sweden.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomsmedicinska kliniken US.
    Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life2009Ingår i: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, nr 3, s. 349-354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

    MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

    RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

    CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

  • 8.
    Ahmadi, Ahmad
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fredriksson, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Jerregård, H.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Åkerbäck, Anita
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fall, Per-Arne
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    Rannug, A.
    National Institute for Working Life, Solna and Inst. of Environ. Medicine, Karolinska Institutet, Stockholm, Sweden.
    Axelson, Olav
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset2000Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 269, nr 3, s. 676-680Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.

  • 9.
    Alfredsson, Joakim
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Clayton, Tim
    London School Hyg and Trop Med, England.
    Damman, Peter
    University of Amsterdam, Netherlands.
    Fox, Keith A. A.
    Royal Infirm, Scotland.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Lagerqvist, Bo
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    Wallentin, Lars
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    de Winter, Robbert J.
    University of Amsterdam, Netherlands.
    Swahn, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes2014Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, nr 4, s. 522-529Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

  • 10.
    Andersson, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten.
    Östholm Balkhed, Åse
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Holmbom, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Hällgren, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Berg, Sören
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Hanberger, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting2019Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, nr 7, s. 1223-1234Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.

  • 11.
    Axelson, Olav
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Östergötlands Läns Landsting, Smärt- och yrkesmedicinskt centrum, Yrkes- och miljömedicinskt centrum.
    Forastiere, Francesco
    Fredrikson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin.
    Assessing dose-response relationships by cumulative exposures in epidemiological studies2007Ingår i: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 50, nr 3, s. 217-220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: If the occurrence of disease monotonically increases with the degree of exposure in an epidemiologic study, a dose-response (or exposure-response) relationship is indicated and facilitates the interpretation that the exposure has a causal role. It is not uncommon, however, that there is some effect in terms of an overall increased relative risk but no clear dose-response relationship. Methods: Models presented here show that cumulative exposure, as involving the duration of exposure, is not an adequate parameter when more recent exposure or the intensity of the exposure plays the greater role for the disease outcome. Conclusions: In lack of a dose-response pattern by cumulative exposure, the interpretation of an overall increased risk might well be that there is no definite effect. The proper consideration should be, however, that the measure of exposure could be inadequate, suggesting a need for further analyses and evaluations of the material studied. © 2007 Wiley-Liss, Inc.

  • 12.
    Axelson, Olav
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Östergötlands Läns Landsting, Smärt- och yrkesmedicinskt centrum, Yrkes- och miljömedicinskt centrum.
    Fredrikson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Östergötlands Läns Landsting, Smärt- och yrkesmedicinskt centrum, Yrkes- och miljömedicinskt centrum.
    Åkerblom, G
    Hardell, L
    Leukemia in childhood and adolescence and exposure to ionizing radiation in homes built from uranium-containing alum shale concrete2002Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 13, nr 2, s. 146-150Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Concerns in Sweden about indoor radon around 1980 prompted measurements of gamma-radiation from the facades of houses to identify those constructed of uranium-containing alum shale concrete, with potentially high radon concentrations. To evaluate any possible risk of acute lymphocytic leukemia from exposure to elevated gamma-radiation in these homes, we identified the acute lymphocytic leukemia cases less than 20 years of age in Sweden during 1980-1989 as well as eight controls per case from the population registry, matching on age, gender, and county. Using the existing measurements, exposure was assessable for 312 cases and 1,418 controls from 151 properly measured municipalities. A conditional logistic odds ratio of 1.4 (95% confidence interval = 1.0-1.9) was obtained for those ever having lived in alum shale concrete houses, with the average exposure exceeding 0.10 microsieverts per hour. Comparing those who ever lived in alum shale concrete houses (divided by higher and lower annual average exposure) with those who never lived in such houses, we found a weak dose-response relation. The results suggest some risk of acute lymphocytic leukemia from indoor ionizing radiation among children and young adults.

  • 13.
    Backstrom, D.
    et al.
    Östergötlands Läns Landsting, Anestesi- och operationscentrum, Anestesi- och intensivvårdskliniken VIN.
    Al-Ayoubi, Fawzi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och operationkliniken US.
    Letter: Outcome of trauma patients2010Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 54, nr 7, s. 902-903Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 14.
    Berkius, Johan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Department of Anaesthesia and Intensive Care, Västervik County Hospital, Västervik, Sweden.
    Engerström, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Orwelius, Lotti
    Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och intensivvårdskliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping,.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten M
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland. Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet.
    A prospective longitudinal multicentre study of health related quality of life in ICU survivors with COPD2013Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, nr 5, s. R211-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Mortality amongst COPD patients treated on the ICU is high. Health-related quality of life (HRQL) after intensive care is a relevant concern for COPD patients, their families and providers of health care. Still, there are few HRQL studies after intensive care of this patient group. Our hypothesis was that HRQL of COPD patients treated on the ICU declines rapidly with time.

    METHODS: Fifty-one COPD patients (COPD-ICU group) with an ICU stay longer than 24 hours received a questionnaire at 6, 12 and 24 months after discharge from ICU. HRQL was measured using two generic instruments: the EuroQoL instrument (EQ-5D and EQ-VAS) and the Short Form 36 Health Survey (SF-36). The results were compared to HRQL of two reference groups from the general population; an age- and sex-adjusted reference population (Non-COPD reference) and a reference group with COPD (COPD reference).

    RESULTS: HRQL of the COPD-ICU group at 6 months after discharge from ICU was lower compared to the COPD reference group: Median EQ-5D was 0.66 vs. 0.73, P=0.08 and median EQ-VAS was 50 vs.55, P<0.05. There were no significant differences in the SF-36 dimensions between the COPD-ICU and COPD-reference groups, although the difference in physical functioning (PF) approached statistical significance (P=0.059). Patients in the COPD-ICU group who were lost to follow-up after 6 months had low HRQL scores at 6 months. Scores for patients who died were generally lower compared to patients who failed to respond to the questionnaire. The PF and social functioning (SF) scores in those who died were significantly lower compared to patients with a complete follow up. HRQL of patients in the COPD-ICU group that survived a complete 24 months follow up was low but stable with no statistically significant decline from 6 to 24 months after ICU discharge. Their HRQL at 24 months was not significantly different from HRQL in the COPD reference group.

    CONCLUSIONS: HRQL in COPD survivors after intensive care was low but did not decline from 6 to 24 months after discharge from ICU. Furthermore, HRQL at 24 months was similar to patients with COPD who had not received ICU treatment.

  • 15.
    Berkius, Johan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Sundh, J
    Örebro University Hospital, Sweden .
    Nilholm, L
    Örebro University Hospital, Sweden .
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    What determines immediate use of invasive ventilation in patients with COPD?2013Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, nr 3, s. 312-319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The choice between non-invasive ventilation (NIV) and invasive ventilation in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may be irrational. The aim of this study was to examine those patient characteristics, and circumstances deemed important in the choice made between NIV and invasive ventilation in the intensive care unit (ICU). Methods We first examined 95 admissions of AECOPD patients on nine ICUs and identified variables associated with invasive ventilation. Thereafter, a questionnaire was sent to ICU personnel to study the relative importance of different factors with a possible influence on the decision to use invasive ventilation at once. Results Univariable analysis showed that increasing age [odds ratio (OR) 1.06 per year] and increasing body mass index (BMI) (OR 1.11 per kg/m2) were associated with immediate invasive ventilation, while there was no such association with arterial blood gases or breath rate. BMI was the only factor that remained associated with immediate invasive ventilation in the multivariable analysis [OR 1.12 (95% confidence interval 1.031.23) kg/m2]. Ranking of responses to the questionnaire showed that consciousness, respiratory symptoms and blood gases were powerful factors determining invasive ventilation, whereas high BMI and age were ranked low. Non-patient-related factors were also deemed important (physician in charge, presence of guidelines, ICU workload). Conclusion Factors other than those deemed most important in guidelines appear to have an inappropriate influence on the choice between NIV and immediate intubation in AECOPD in the ICU. These factors must be identified to further increase the appropriate use of NIV.

  • 16.
    Berkius, Johan
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Sundh, Josefin
    Orebro University Hospital.
    Nilholm, Lennart
    Orebro University Hospital.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Long-term survival according to ventilation mode in acute respiratory failure secondary to chronic obstructive pulmonary disease: A multicenter, inception cohort study2010Ingår i: JOURNAL OF CRITICAL CARE, ISSN 0883-9441, Vol. 25, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aim of the study was to investigate 5-year survival stratified by mechanical ventilation modality in chronic obstructive pulmonary disease (COPD) patients treated in the ICU. Materials and Methods: Prospective, observational study of COPD patients with acute respiratory failure admitted to 9 multidisciplinary ICUs in Sweden. Characteristics on admission, including illness severity scores and the first blood gas, and survival were analyzed stratified by ventilation modality (noninvasive [NIV] vs invasive mechanical ventilation). Results: Ninety-three patients, mean age of 70.6 (SD, 9.6) years, were included. Sixteen patients were intubated immediately, whereas 77 were started on NIV. Patients who were started on NIV had a lower median body mass index (BMI) (21.9 vs 27.0; P andlt; .01) and were younger compared to those who were intubated immediately (median age, 70 vs 74.5 years; P andlt; .05). There were no differences in the initial blood gas results between the groups. Long-term survival was greater in patients with NIV (P andlt; .05, log rank). The effect of NIV on survival remained after including age, Acute Physiology and Chronic Health Evaluation II score, and BMI in a multivariate Cox regression model (NIV hazard ratio, 0.44; 95% confidence interval, 0.21-0.92). Fifteen patients with failed NIV were intubated and mechanically ventilated. Long-term survival in patients with failed NIV was not significantly different from patients who were intubated immediately. Conclusion: The short-term survival benefit of NIV previously found in randomized controlled trials still applies after 5 years of observation.

  • 17.
    Boström, A.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Thulin, K.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping.
    Fredriksson, Mats
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap.
    Reese, D.
    IFK Norrköping, Norrköping, Sweden.
    Rockborn, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old: What about resistance training with weights?2016Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, nr 3, s. 317-323Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.

  • 18.
    Bragde, Hanna
    et al.
    Ryhov County Hospital, Sweden.
    Jansson, Ulf
    Ryhov County Hospital, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Grodzinsky, Ewa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Soederman, Jan
    Ryhov County Hospital, Sweden.
    Potential blood-based markers of celiac disease2014Ingår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 14, nr 176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. Methods: We investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann-Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis. Results: CXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-kappa B complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone. Conclusions: The CD markers identified in this study further emphasize the significance of components related to NF-kappa B regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-kappa B interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD.

  • 19.
    Bragde, Hanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Ryhov Cty Hosp, Sweden.
    Jansson, Ulf
    Ryhov Cty Hosp, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Grodzinsky, Ewa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Division of Forensic Genetics & Forensic Toxicology National Board of Forensic Medicine Linköping, Sweden.
    Söderman, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Ryhov Cty Hosp, Sweden.
    Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies2018Ingår i: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 75, nr 23, s. 4385-4401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n=20) or without any signs of CD (n=20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n=43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis.

  • 20.
    Bäckman, Carl G
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Orwelius, Lotti
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten M
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    A case-control study of the influence of the ICU-diary concept on mastery and hopelessness six months after critical illnessManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The ICU-diary concept is associated with less post-traumatic stress syndrome and improved perceived health-related quality-of-life (HRQoL) after critical illness, but little is known about its effect on the coping- mastery process, or whether it reduces hopelessness.

    Objective: To see if the ICU-diary concept improves the patient’s ability to master his/her situation after critical illness, and if it reduces the feeling of hopelessness.

    Design: Case control study (subgroup analysis of a multi-centre study on health-related quality-of-life (HRQoL).

    Setting: Non-academic 8-bed general ICU.

    Patients: Adults admitted between March 2002 and June 2004.

    Measurements: Mastery and hopelessness were determined using validated questionnaires (the Mastery-Coping scale and a consolidated 2–item hopelessness questionnaire) which were sent home to patients 6 months after critical illness. Responses were compared between patients that received (Cases: n=38) or did not receive an ICU-diary (Controls: n=76) . Diaries were used when a long and complicated stay on the ICU was expected. Controls were matched with diary patients by gender and age. The effect of the ICU-diary was also examined using a multiple regression model.

    Results: The ICU-diary concept group scored significantly higher than the No-diary group in mastery (22.1 vs. 20.4, P<0.05) and lower in hopelessness scores (1.3 vs. 1.6, P<0.05). The positive influence of the ICU-diary disappeared after adjustment for confounding factors in a multiple regression model.

    Conclusion: We were unable to verify any positive influence of the ICU-diary concept on mastery and hopelessness 6 months after critical illness.

  • 21.
    Bäckman, Carl
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Orwelius, Lotti
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och operationkliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Long-term effect of the ICU-diary concept on quality of life after critical illness2010Ingår i: ACTA ANAESTHESIOLOGICA SCANDINAVICA, ISSN 0001-5172, Vol. 54, nr 6, s. 736-743Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Critically ill patients often spend time in the intensive care unit (ICU) either unconscious or sedated. On recovery, they are often in a state of confusion with memory loss that may be associated with a longstanding reduction in health-related quality of life (QoL). We hypothesised that the ICU-diary concept could improve their QoL by filling in their memory gaps. Methods A non-randomised, prospective study in a non-academic eight-bedded general ICU. A group of patients (n=38) were selected to receive the ICU-diary concept (keeping a diary with photos while on the ICU plus a follow-up meeting) when a long and complicated course was expected. Health-related QoL at 6, 12, 24 and 36 months was compared with a group that did not receive the ICU-diary (n=224). The Medical Outcomes Study 36-Item Short-Form (SF-36) was used to measure health-related QoL. Multiple regression models adjusted for age, sex, illness severity, pre-existing disease and diagnostic category was used to analyse the effects of the ICU-diary concept at 6 months, and changes over time were analysed using repeated measures MANOVA. Results Crude and adjusted scores for two dimensions of SF-36 (general health and vitality) and the physical component summary score were significantly higher at 6 months in the ICU-diary group (P andlt; 0.05) and some of the effects remained during the 3-year follow-up period (P andlt; 0.05). Conclusion The ICU-diary concept was associated with improved health-related QoL during the 3-year follow-up period after a critical illness. The effect of this intervention needs to be confirmed in a larger randomised study.

  • 22.
    Bäckström, Denise
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Larsen, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Steinvall, Ingrid
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gedeborg, Rolf
    Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden..
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing2018Ingår i: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 44, nr 4, s. 589-596Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage.

    METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression.

    RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r (2) = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r (2) = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r (2) = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r (2) = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r (2) = 0.84; p < 0.001) and poisoning (coefficient 0.13, r (2) = 0.69; p < 0.001).

    CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

  • 23.
    De Geer, Lina
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Oscarsson Tibblin, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Anestesiologi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study2012Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 29, nr 6, s. 275-279Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. Objective: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Design: Prospective, observational cohort study. Setting: A mixed noncardiothoracic tertiary ICU in Sweden. Patients and main outcome measures NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearmans correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. Results: An NT-pro-BNP more than 1380 ng l(-1) on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng l(-1), and 14.6% of patients below that threshold died within 30 days (log rank P 0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearmans rho 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). Conclusion: We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.

  • 24.
    De Geer, Lina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Oscarsson, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Cardiac mortality after septic shock.2015Konferensbidrag (Refereegranskat)
  • 25.
    De Geer, Lina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Oscarsson, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Walther, Sten M.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Cardiac mortality after severe sepsis and septic shock: A nationwide observational cohort study2015Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences remain unclear. The aim of this study was to investigate cardiac outcome after sepsis by assessing causes of death in a nationwide register-based cohort.

    Methods: A cohort of 9,520 severe sepsis and septic shock intensive care (ICU) patients without preceding severe cardiac failure and discharged alive from the ICU was collected from the Swedish Intensive Care Registry (SIR) from 2008 to 2013, together with a nonseptic control group (n = 4,577). Patients were matched according to age, sex and severity of illness. Information on cause of death after ICU discharge was sought in the Swedish National Board of Health and Welfare’s Cause of Death Registry.

    Results: After ICU discharge, 3,954 (42%) of severe sepsis or septic shock patients died. In 654 (16%) of these, cardiac failure was registered as the cause of death. The follow-up time was 17,693 person-years (median 583 days/person; maximum 5.7 years) and the median (IQR) time from ICU discharge to cardiac failure-related death 81 (17 - 379) days. With increasing severity of illness (quartiles of SAPS3), the hazard rate for cardiac failure-related death increased (hazard ratio (HR) 1.58 (95% CI 1.19 - 2.09, p <0.001) in the highest quartile compared to the lowest). In a matched comparison between severe sepsis or septic shock patients and controls, survival was similar, and the hazard rate for cardiac failurerelated death did not differ between groups (HR 0.97, 95% CI 0.88 – 1.10, p = 0.62).

    Conclusions: The risk of death with cardiac failure as the cause of death after severe sepsis or septic shock increases with severity of illness on admission. Patients with severe sepsis or septic shock are not, however, at an increased risk of death with cardiac failure as the cause of death when compared to other ICU patients with similar severity of illness.

  • 26.
    de Geer, Lina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Oscarsson Tibblin, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Walther, Sten M.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    No association with cardiac death after sepsis: A nationwide observational cohort study2019Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, nr 3, s. 344-351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry.

    METHODS: A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry.

    RESULTS: Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P < 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison.

    CONCLUSIONS: There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.

  • 27.
    Dellerantz, E
    et al.
    Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Martner, J
    University of Gothenburg.
    Nolin, T
    Central Hospital Kristianstad.
    Wickerts, C-J
    Danderyds Sjukhus.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    LONG-TERM OUTCOME AFTER CARDIAC ARREST TREATED WITH THERAPEUTIC HYPOTHERMIA: RESULTS FROM THE SWEDISH INTENSIVE CARE REGISTRY2009Ingår i: in INTENSIVE CARE MEDICINE, vol 35, 2009, Vol. 35, s. 180-180Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 28.
    Ehsan Saffari, Seyed
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Sabzevar University of Medical Science, Iran.
    Love, Askell
    Lund University, Sweden; Landspitali University Hospital, Iceland; University of Iceland, Iceland.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. KTH Royal Institute Technology, Sweden.
    Regression models for analyzing radiological visual grading studies - an empirical comparison2015Ingår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 15, nr 49Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: For optimizing and evaluating image quality in medical imaging, one can use visual grading experiments, where observers rate some aspect of image quality on an ordinal scale. To analyze the grading data, several regression methods are available, and this study aimed at empirically comparing such techniques, in particular when including random effects in the models, which is appropriate for observers and patients. Methods: Data were taken from a previous study where 6 observers graded or ranked in 40 patients the image quality of four imaging protocols, differing in radiation dose and image reconstruction method. The models tested included linear regression, the proportional odds model for ordinal logistic regression, the partial proportional odds model, the stereotype logistic regression model and rank-order logistic regression (for ranking data). In the first two models, random effects as well as fixed effects could be included; in the remaining three, only fixed effects. Results: In general, the goodness of fit (AIC and McFaddens Pseudo R-2) showed small differences between the models with fixed effects only. For the mixed-effects models, higher AIC and lower Pseudo R-2 was obtained, which may be related to the different number of parameters in these models. The estimated potential for dose reduction by new image reconstruction methods varied only slightly between models. Conclusions: The authors suggest that the most suitable approach may be to use ordinal logistic regression, which can handle ordinal data and random effects appropriately.

  • 29.
    Ekman, Anna-Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Verma, Deepti
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Bivik, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Enerbäck, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Genetic variations of NLRP1: susceptibility in psoriasis2014Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, nr 6, s. 1517-1520Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.

    OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.

    MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.

    RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.

    CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

  • 30.
    Ekstedt, Mattias
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hagström, Hannes
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Nasr, Patrik
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Stal, Per
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hultcrantz, Rolf
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm.
    Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY2016Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, nr 1, s. 310-311Artikel i tidskrift (Refereegranskat)
  • 31.
    Ekstedt, Mattias
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hagström, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Stål, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up2015Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, nr 5, s. 1547-1554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.

  • 32.
    Engerström, Lars
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Kramer, Andrew A.
    Prescient Healthcare Consulting, Charlottesville, VA.
    Nolin, Thomas
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Karlström, Göran
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Academic Research Center, Linköping University, Linköping, Sweden.
    Walther, Sten M
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Comparing Time-Fixed Mortality Prediction Models and Their Effect on ICU Performance Metrics Using the Simplified Acute Physiology Score 3.2016Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, nr 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference.

    DESIGN: Retrospective cohort study of ICU admissions from 2010 to 2014.

    SETTING: Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry.

    PATIENTS: The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729).

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping (< 1.00, not significant, > 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs.

    CONCLUSIONS: The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

  • 33.
    Engerström, Lars
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nolin, Thomas
    Central Hospital Kristianstad, Sweden.
    Mårdh, Caroline
    Landstinget Värmland, Sweden.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Karlström, Göran
    Landstinget Varmland, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten, Forum Östergötland.
    Walther, Sten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model*2017Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, nr 12, s. 2006-2013Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 models performance. Design: Retrospective analysis of prospectively collected data. Setting: Sixty-three ICUs in the Swedish Intensive Care Registry. Patients: Patients admitted during 2011-2014 (n = 107,310). Interventions: None. Measurements and Main Results: Model performance was analyzed using the area under the receiver operating curve, scaled Briers score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. Conclusions: There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

  • 34.
    Fall, Per-Arne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Axelson, Olav
    Linköpings universitet, Institutionen för molekylär och klinisk medicin.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Hansson, Gunilla
    Lindvall, Björn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Jan-Edvin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Granérus, Ann-Kathrine.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Age standardised incidence and prevalence of Parkinson´s disease in a Swedish community1996Ingår i: Journal of Clinical Epidemiology, ISSN 0895-4356, Vol. 49, nr 6, s. 637-641Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Parkinson's disease (PD) shows a geographical variation. All prescriptions for anti-parkinsonian drugs were recorded for a half-year in a region with low -dopa consumption. Hospital and outpatient records were studied and physicians were asked to supply details of PD patients in the region, with 147,777 inhabitants. The crude prevalence was 115 PD per 100,000 inhabitants, based on 170 cases. In contrast to other studies we report an age-standardized prevalence, which was 76 per 100,000, using the European Standard Population as reference. The corresponding approximate incidences were 11.0 (crude) and 7.9 (age-standardized) per 100,000 person-years. Male preponderance appeared in all age groups. Mean age at onset was 65.6 years, the highest figure reported. Variation between studies for age at onset, differences in prevalence, and male preponderance suggest environmental risk factors to be of importance for PD.

  • 35.
    Fall, Per-Arne
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Axelson, Olav
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Arbets- och miljömedicin.
    Granérus, Ann-Kathrine.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden1999Ingår i: Movement Disorders, ISSN 0885-3185, Vol. 14, nr 1, s. 28-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE AND METHODS: To investigate the possible impact of nutritional and environmental risk factors for idiopathic Parkinson's disease (IP), a case-control study was performed in the county of Ostergötland in southeastern Sweden. The study involved 113 cases of IP and 263 control subjects. Dietary, drinking, and smoking habits, as well as previous occupation, were requested in a structured questionnaire.

    RESULTS: No increased risk was found for any of the nutritional items in which information was requested. A reduced risk was found for coffee, wine, and liquor at various consumption levels but also for fried or broiled meat, smoked ham or meat, eggs, French loaf or white bread, and tomatoes. All these food and drink items contain niacin. As in many studies, the frequency of preceding and present smoking was reduced in IP patients. Various occupational groups and exposures were analyzed and increased risks of IP in men were found for agricultural work along with pesticide exposure; this was also the case for male carpenters and female cleaners.

    CONCLUSIONS: The findings indicate that nutritional factors and occupational exposures, especially to pesticides, could be of etiologic importance in IP.

  • 36.
    Fall, Per-Arne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Saleh, Avin
    Fredrikson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin.
    Olsson, Jan-Edvin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Granerus, Ann-Kathrine
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Survival time, mortality, and cause of death in elderly patients with Parkinson's disease: A 9-year follow-up2003Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 18, nr 11, s. 1312-1316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This community-based study of Parkinson's disease (PD) investigated age at death and cause of death in a cohort of 170 previously studied patients. The current study is a 9-year follow-up, and the results are compared to 510 sex- and age-matched controls from the same area. A total of 170 patients were diagnosed with PD on August 31, 1989, within a defined area of Sweden. A control group of 510 persons from the same area and with the same age and sex distribution was also examined regarding age at death and cause of death. After 9.4 years, 121 cases (71.1%) and 229 controls (44.9%) were no longer alive. Thus, the mortality rate ratio was 1.6 (95% confidence interval [CI], 1.3-1.8) when comparing PD patients with controls. The all-cause hazard ratio for cases compared to controls was 2.4 (95% CI, 1.9-3.0). The mean age at death for the cases was 81.9 (95% CI, 80.3-83.0) years and for the controls 82.9 (95% CI, 82.0-83.7) years. Survival analysis also showed a shorter survival time (P < 0.001) for PD patients. Only 53% of the death certificates for the deceased patients recorded PD as an underlying or contributory cause of death. Many PD patients reached a high age but had a shorter survival than the controls. There was a significant increase in deaths from pneumonia.

  • 37.
    Farnebo, Lovisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US. Linköpings universitet, Medicinska fakulteten.
    Stjernstrom, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ansell, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Thunell, Lena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck2015Ingår i: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 31, s. 64-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a high rate of early recurrences, second primary tumors, and mortality. Despite advances in diagnosis and treatment over the past decades, the overall 5-year survival rate remains around 50%. Since the head-and neck-region is continuously exposed to potentially DNA-damaging exogenous and endogenous factors, it is reasonable to expect that the DNA repair genes play a part in the development, progression, and outcome of HNSCC. The aim of this study was to investigate the SNPs XPC A499V, XPD K751Q XRCC1 R399Q and XRCC3 T241M as potential risk factors and indicators of survival among Caucasian patients. One-hundred-sixty-nine patients as well as 344 healthy controls were included and genotyped with PCR-RFLP. We showed that XPC A499V was associated with increased risk of HNSCC, especially laryngeal carcinoma. Among women, XPD K751Q was associated with increased risk of oral SCC. Furthermore, XPD homozygous mutant individuals had the shortest survival time, a survival time that increased however after full dose radiotherapy. Wild-type individuals of XRCC3 T241M demonstrated an earlier age of onset. HPV-positive never smokers had lower frequencies of p53 mutation. Among HNSCC patients, HPV-positivity was significantly associated with XRCC1 R399Q homozygous mutant genotype. Moreover, combinations of putative risk alleles seemed to act synergistically, increasing the risk of HNSCC. In conclusion, our results suggest that SNPs of the DNA repair genes XPC, XPD, XRCC1, and XRCC3 may affect risk and survival of HNSCC. (C) 2015 Elsevier B.V. All rights reserved.

  • 38.
    Fransén, Karin
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fenech, Matthew
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Association between ulcerative growth and hypoxia inducible factor-1α polymorphisms in colorectal cancer patients2006Ingår i: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 45, nr 11, s. 833-840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hypoxia inducible factor-1α (HIF-1α) has been found to be involved in several different physiological mechanisms, such as blood-vessel formation, apoptosis, and erythropoiesis. HIF-1α is hydroxylated at normoxia and rapidly degraded via the von Hippel–Lindau (VHL)/ubiquitin-proteasome degradation system to prevent angiogenesis. In a previous study, the C1772T (P582S) and the G1790A (A588T) polymorphisms were identified in the human HIF-1α gene, which was shown to have a higher transactivating capability in vitro compared to the wild type allele. However, the role for these polymorphisms in vivo is still unclear. In the present investigation, we have therefore studied the role of the two polymorphic variants in the development of colorectal cancer (CRC) with PCR/RFLP (restriction fragment length polymorphism), single strand conformation analysis (SSCA), and immunohistochemistry (IHC). A significant higher-risk was identified between patients heterozygous for the C1772T polymorphism and the more severe ulcerative growth pattern compared to homozygous C1772C wild type tumors (RR = 5.2; 95% CI 1.26–21.6; P = 0.006). This was also verified on the allelic level (RR = 6.5; 95% CI 1.58–26.8; P = 0.001). In addition, patients carrying one or more polymorphic alleles in either the HIF-1α C1772T or the G1790A polymorphisms display significant higher risk for the development of ulcerative CRCs (RR = 4.17; 95% CI = 1.33–13.08; P = 0.004). These results suggest that the HIF-1α polymorpisms are an important factor for development of a subset of ulcerative intestinal tumors. Future screening of the polymorphic HIF-1α allele may therefore be of importance in the selection of treatment strategies of CRC.

  • 39.
    Frisk, Jessica
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Källström, Ann-Christine
    Clinical Department of Surgery, Division of Oncology, Helsingborg Hospital, Helsingborg, Sweden.
    Wall, Najme
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Acupuncture improves health-related quality-of-life (HRQoL) and sleep in women with breast cancer and hot flushes2012Ingår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 20, nr 4, s. 715-724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Evaluate effects of electro-acupuncture (EA) and hormone therapy (HT) on health-related quality-of-life (HRQoL) and sleep in breast cancer survivors with vasomotor symptoms.

    METHODS: Forty-five women, randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months, were followed for up to 2 years. Distress caused by, and numbers of, hot flushes, hours slept and times woken up/night, Psychological and General Well-being Index (PGWB) and Women's Health Questionnaire (WHQ) were registered before and during treatment and at 6, 9, 12, 18 and 24 months after start of treatment.

    RESULTS: After 12 weeks of EA (n = 19), WHQ improved from 0.32 (IQR 0.23-0.53) at baseline to 0.24 (IQR 0.12-0.39; p < 0.001) and PGWB from 78 (IQR 53-89) to 79 (IQR 68-93; p = 0.002). All sleep parameters improved and Hot Flush Score (HFS) decreased by 80%. At 12 months, WHQ, PGWB and all sleep parameters remained significantly improved (n = 14) and HFS decreased by 65%. After 12 weeks of HT (n = 18), WHQ improved from 0.29 (IQR 0.15-0.44) at baseline to 0.15 (IQR 0.05-0.22; p = 0.001), PGWB from 75 (IQR 59-88) to 90 (62-97; p = 0.102) and three of five sleep parameters improved.

    CONCLUSION: Both EA and HT increased HRQoL and sleep, probably through decreasing numbers of and distress by hot flushes. Although flushes decreased less in the EA group than in the HT group, HRQoL improved at least to the same extent maybe due to other effects of EA, not induced by HT, e.g. on anxiety, vitality and sleep, supported by subscale analyses. EA should be further evaluated as treatment for women with breast cancer and climacteric complaints, since HT no longer can be recommended for these women.

  • 40.
    Gladh, Mathias
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi.
    Rahgozar, Mohammad
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi.
    Hammar, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Fredrikson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin.
    Spetz, Anna-Clara
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi.
    Prevalence of symptoms possibly related to PADAM, in a Swedish population aged 55, 65 and 75 years2005Ingår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 50, nr 3, s. 161-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: With age there is an average decline in the concentration of biologically active testosterone. It is still controversial if this leads to a clinically relevant deficit, "partial androgen deficiency of the ageing man" (PADAM). Our objective was to investigate the prevalence of a series of symptoms possibly associated with PADAM in an assumed normal-population of older men. Methods: We developed a questionnaire including items about symptoms possibly associated with PADAM as well as background data covering demography, medical history, mood status, medication, castration therapy, as well as smoking, exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to predict low bio-available T, were also included. The questionnaire was sent to all 1885 men 55, 65 or 75-years-old, living in Linköping, Sweden. Results: We identified a number of symptoms that differed significantly (P<0.01) between age groups, e.g., "increased abdominal circumference", "decrease in muscle strength and/or endurance", "decreased libido", "less strong erection" and "lack of energy". From factorial analysis we found that the symptoms co-varied in four different groups. Conclusion: The prevalence of a number of symptoms differed significantly between age groups, but we cannot infer that there is a causal connection between an average age-dependent decline in testosterone function and these symptoms. There are several other ways to interpret these results like the existence of concurrent somatic and/or mood disorders or ageing as such. For this purpose further studies including measurements of testosterone concentrations relating to the findings of this study have to be performed. © 2004 Elsevier Ireland Ltd. All rights reserved.

  • 41.
    Graff, Pal
    et al.
    Orebro Univ, Sweden; Natl Inst Occupat Hlth STAMI, Norway.
    Bryngelsson, Ing-Liss
    Orebro Univ, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Flodin, Ulf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Adult onset asthma in non-allergic women working in dampness damaged buildings: A retrospective cohort study2019Ingår i: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 62, nr 4, s. 357-363Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background There is still no consensus about the association between working in dampness-damaged buildings and new onset of asthma among adults. The purpose of this study was to assess asthma in the staff of two psychiatric clinics where some premises were suffering from dampness. Methods A 20-year retrospective cohort study was performed using questionnaires. Results Incidence rate ratios (IRR) for asthma were non-significantly elevated (IRR = 2.3) among exposed individuals. The risk was greater among females (IRR = 3.5, 95% CI 1.0-16). IRR for non-atopic women was 8.8 (95% CI 1.4-196). Adjusting for smoking habits weakened the risks marginally (IRR = 7.3, 95% CI 1.1-167). The number of male participants was too low to draw conclusion regarding the risk for men. Conclusion The results suggest that working in dampness-damaged buildings might be a possible health hazard. This finding is most pronounced in non-atopic females.

  • 42.
    Graff, Pål
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Flodin, Ulf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Non-sensitising air pollution at workplaces and adult-onset asthma in the beginning of this millennium2011Ingår i: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 84, nr 7, s. 797-804Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men.

  • 43.
    Guldbrand, Hans
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Dizdar, B.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Bunjaku, B.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet.
    Bachrach-Lindström, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Nyström, Fredrik H.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Institutionen för medicin och hälsa, Endokrinologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss2012Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, nr 8, s. 2118-2127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n = 31); LCD -4.31 ± 3.6 kg (n = 30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.

  • 44.
    Götmar, Anders
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Samsioe, Göran
    Departments of Clinical Sciences in Lund and Malmö, Lund University, Sweden.
    Nerbrand, Christina
    Departments of Clinical Sciences in Lund and Malmö, Lund University, Sweden.
    Lidfeldt, Jonas
    Departments of Clinical Sciences in Lund and Malmö, Lund University, Sweden.
    Spetz, Anna-Clara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Symptoms in peri- and postmenopausal women in relation to testosterone concentrations. Data fromThe Women's Health in the Lund Area (WHILA) study2008Ingår i: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 11, nr 4, s. 304-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this study was to investigate possible associations between androgen concentrations in perimenopausal women and symptoms that may be associated with low androgen concentrations in the blood.

    Methods: All women born 1935 to 1945 living in a defined geographic area in Sweden (n=10766) were invited to a screening program that included physical and laboratory examinations and a questionnaire. Three groups were identified; premenopausal women, women on hormone replacement therapy (HRT) and postmenopausal women without HRT. Concentrations of testosterone (T), androstendione, Sex Hormone Binding Globulin and estradiol were measured. Waist Hip Ratio, Body Mass Index and Free Testosterone Index (FTI) were calculated.

    Results: 6908 women participated. The women on HRT had lower T and FTI and were less satisfied with mood and energy (p<0.05). Women with hot flushes had higher T and FTI and women reporting coldness had lower concentrations (p<0.05). Sexual well-being were not correlated to T or FTI (p>0.05).

    Conclusions: Lower T concentrations were associated with lower quality of life in perimenopausal women but not to sexual well-being. There must be other factors than decrements in sex hormones that contribute to the emergence of some perimenopausal symptoms.

  • 45.
    Hanberger, Håkan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ternhag, Anders
    Swedish Institute Communicable Disease Control, Sweden .
    Giske, Christian G.
    Karolinska University Hospital, Sweden .
    Letter: Rational use of aminoglycosides - author response2013Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, nr 8, s. 655-656Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 46.
    Helmfrid, Ingela
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Ljunggren, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Nosratabadi, Ali Reza
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Augustsson, Anna
    Linnaeus University, Kalmar, Sweden.
    Filipsson, Monika
    Linnaeus University, Kalmar, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Helen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Berglund, Marika
    Karolinska Institutet, Stockholm, Sweden.
    Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glasswork area2019Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 131, artikel-id UNSP 104985Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.

    Objective

    The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.

    Methods

    The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.

    Results

    Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.

    Conclusions

    The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

  • 47.
    Hjelm, Carina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Broström, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurofysiologiska kliniken US. Jönköping University.
    Dahl, Anna
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Boo
    Department of Psychology, University of Gothenburg, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Strömberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Factors Associated With Increased Risk for Dementia in Individuals Age 80 Years or Older With Congestive Heart Failure2014Ingår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 29, nr 1, s. 82-90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND RESEARCH OBJECTIVE:: An increasing body of evidence shows that individuals diagnosed with congestive heart failure (CHF) are at a higher risk for dementia. However, the prevalence rate of dementia among persons with CHF in very old individuals has not been previously reported, and little is known about the comorbidities that place old persons with CHF at a higher risk for dementia. The aim of this study was to compare the prevalence of dementia in individuals 80 years or older who have CHF with that in individuals without CHF and to identify factors related to dementia in individuals diagnosed with CHF.

    METHODS:: A total of 702 participants from a Swedish population-based longitudinal study (Octogenerian Twin) were included. The group consisted of same-sex twin pairs, age 80 years or older, and 138 participants had CHF. Dementia was diagnosed according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Generalized estimating equations including gender, age and educational level, waist circumference, diabetes, hypertension, smoking, depression, and blood values were used in a case-control analysis.

    RESULTS:: Individuals with CHF had a significantly higher prevalence of vascular dementia, 16% vs 6% (P < 0.001), and of all types of dementia, 40% vs 30% (P < 0.01), than those not diagnosed with CHF. The generalized estimating equation models showed that depression, hypertension, and/or increased levels of homocysteine were all associated with a higher risk for dementia in individuals with CHF. Diabetes was specifically associated with an increased risk for vascular dementia.

    CONCLUSIONS:: The prevalence of dementia was higher among individuals with CHF than in those without CHF. Diabetes, depression, and hypertension in patients with CHF require special attention from healthcare professionals because these conditions are associated with an elevated risk for dementia. Higher levels of homocysteine were also found to be a marker of dementia in patients with CHF. Further research is needed to identify the factors related to dementia in individuals 80 years or older diagnosed with CHF.

  • 48.
    Holmbom, Martin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Giske, Christian G.
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden..
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Östholm Balkhed, Åse
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Claesson, Carina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Lennart E
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Hoffmann, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Hanberger, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    14-Year Survey in a Swedish County Reveals a Pronounced Increase in Bloodstream Infections (BSI). Comorbidity: An Independent Risk Factor for Both BSI and Mortality2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county.

    Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI).

    Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04).

    Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics.

  • 49.
    Huang-Link, Yu-Min
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Link, Hans
    Karolinska Institute, Sweden.
    Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes2015Ingår i: JOURNAL OF CLINICAL NEUROLOGY, ISSN 1738-6586, Vol. 11, nr 3, s. 241-247Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON). Methods Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs. Results The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54 +/- 0.24 and -0.43 +/- 0.21 mu m/year, mean SE; pless than0.05 for both), and not in non-ON BMS (-0.11 +/- 0.27 and -0.24 +/- 0.24 mu m/year). Conclusions The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.

  • 50.
    Ingves, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Vilhelmsson, Nathalie
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Ström, Edvin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Guldbrand, Hans
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    A randomized cross-over study of the effects of macronutrient composition and meal frequency on GLP-1, ghrelin and energy expenditure in humans2017Ingår i: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 93, s. 20-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Little is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition. Design: Randomized cross-over study with four conditions for each participant. Methods: Seven men and seven women (mean age 23 +/- 1.5 years) were randomly assigned to the order of intake of a 750 kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150 kcal portions every 30 min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30 min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p amp;lt; 0.013 was considered statistically significant following Bonferroni-correction. Results: The area under the curve (AUC) for EE was higher during the 2.5 h after the high-carbohydrate drinks (p = 0.005 by Wilcoxon) and also after ingesting one drink compared with five (p = 0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p = 0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9 +/- 18 pg/ml/h, high-carbohydrate: 45.2 +/- 16 pg/ml/h, p = 0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p = 0.009). Conclusions: We found higher EE during 2.5 h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.

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