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Udumyan, R., Montgomery, S., Duberg, A.-S., Fang, F., Valdimarsdottir, U., Ekbom, A., . . . Fall, K. (2020). Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients. Scandinavian Journal of Gastroenterology
Open this publication in new window or tab >>Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients
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2020 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014.

Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures.

Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); p = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); p = .006], β1-receptor selective [0.86 [0.75-1.00); p = .049] and lipophilic [0.78 (0.67-0.90); p = .001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80-1.28); p = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); p = .062].

Conclusion: β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Register-based cohort study, beta-adrenergic signaling, non-selective beta-blockers, selective beta-blockers, survival analysis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-81928 (URN)10.1080/00365521.2020.1762919 (DOI)32412855 (PubMedID)
Available from: 2020-05-19 Created: 2020-05-19 Last updated: 2020-05-19Bibliographically approved
Sundh, J., Magnuson, A., Montgomery, S., Andell, P., Rindler, G., Fröbert, O., . . . Lokke, A. (2020). Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial. Trials, 21(1), Article ID 123.
Open this publication in new window or tab >>Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
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2020 (English)In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 21, no 1, article id 123Article in journal (Refereed) Published
Abstract [en]

Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.

Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.

Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Beta-blocker, Cardiovascular event, COPD, Exacerbation, Mortality, Pragmatic randomized trial, Real-world evidence
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-80376 (URN)10.1186/s13063-019-3907-1 (DOI)000513538600001 ()32000825 (PubMedID)2-s2.0-85078711805 (Scopus ID)
Funder
Swedish Research Council, 2018-00511
Note

Funding Agencies:

Swedish Respiratory Society  

Uppsala-Örebro Regional Research Council  RFR-851601

Örebro University  ORU 2018/01219

Region Örebro County through ALF research funding  OLL-843061

Available from: 2020-03-04 Created: 2020-03-04 Last updated: 2020-03-04Bibliographically approved
Smith, K. A., Burkill, S., Hiyoshi, A., Olsson, T., Bahmanyar, S., Wormser, D., . . . Montgomery, S. (2020). Comorbid disease burden among MS patients 1968-2012: A Swedish register-based cohort study. Multiple Sclerosis
Open this publication in new window or tab >>Comorbid disease burden among MS patients 1968-2012: A Swedish register-based cohort study
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2020 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden.

OBJECTIVE: To describe lifetime CMD burden among pwMS.

METHODS:  PwMS identified using Swedish registers between 1968 and 2012 (n = 25,476) were matched by sex, age, and county of residence with general-population comparators (n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures.

RESULTS: The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS.

CONCLUSION: Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.

Place, publisher, year, edition, pages
Sage Publications, 2020
Keywords
Multiple sclerosis, Sweden, burden, chronic disease, cohort, comorbidity, prevalence, registries
National Category
Geriatrics
Identifiers
urn:nbn:se:oru:diva-80606 (URN)10.1177/1352458520910497 (DOI)000523823900001 ()32162580 (PubMedID)
Note

Funding Agencies:

Hoffmann-La Roche

Novartis Pharma AG 

Available from: 2020-03-13 Created: 2020-03-13 Last updated: 2020-04-20Bibliographically approved
Kisiel, M. A., Zhou, X., Sundh, J., Ställberg, B., Lisspers, K., Malinovschi, A., . . . Janson, C. (2020). Data-driven questionnaire-based cluster analysis of asthma in Swedish adults. NPD Bulletin, 30(1), Article ID 14.
Open this publication in new window or tab >>Data-driven questionnaire-based cluster analysis of asthma in Swedish adults
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2020 (English)In: NPD Bulletin, ISSN 1892-8110, E-ISSN 2055-1010, Vol. 30, no 1, article id 14Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to identify asthma phenotypes through cluster analysis. Cluster analysis was performed using self-reported characteristics from a cohort of 1291 Swedish asthma patients. Disease burden was measured using the Asthma Control Test (ACT), the mini Asthma Quality of Life Questionnaire (mini-AQLQ), exacerbation frequency and asthma severity. Validation was performed in 748 individuals from the same geographical region. Three clusters; early onset predominantly female, adult onset predominantly female and adult onset predominantly male, were identified. Early onset predominantly female asthma had a higher burden of disease, the highest exacerbation frequency and use of inhaled corticosteroids. Adult onset predominantly male asthma had the highest mean score of ACT and mini-AQLQ, the lowest exacerbation frequency and higher proportion of subjects with mild asthma. These clusters, based on information from clinical questionnaire data, might be useful in primary care settings where the access to spirometry and biomarkers is limited.

Place, publisher, year, edition, pages
Nature Research, 2020
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:oru:diva-81106 (URN)10.1038/s41533-020-0168-0 (DOI)000526433300002 ()32249767 (PubMedID)2-s2.0-85083051775 (Scopus ID)
Funder
Swedish Heart Lung FoundationSwedish Asthma and Allergy Association
Note

Funding Agencies:

County councils of the Uppsala-Örebro Health Care region

Bror Hjerpstedts Foundation  

Center for Clinical Research, Dalarna 

Available from: 2020-04-07 Created: 2020-04-07 Last updated: 2020-04-30Bibliographically approved
Cao, Y., Montgomery, S., Ottosson, J., Näslund, E. & Stenberg, E. (2020). Deep Learning Neural Networks to Predict Serious Complications After Bariatric Surgery: Analysis of Scandinavian Obesity Surgery Registry Data. JMIR medical informatics, 8(5), Article ID e15992.
Open this publication in new window or tab >>Deep Learning Neural Networks to Predict Serious Complications After Bariatric Surgery: Analysis of Scandinavian Obesity Surgery Registry Data
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2020 (English)In: JMIR medical informatics, E-ISSN 2291-9694, Vol. 8, no 5, article id e15992Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Obesity is one of today's most visible public health problems worldwide. Although modern bariatric surgery is ostensibly considered safe, serious complications and mortality still occur in some patients.

OBJECTIVE: This study aimed to explore whether serious postoperative complications of bariatric surgery recorded in a national quality registry can be predicted preoperatively using deep learning methods.

METHODS: Patients who were registered in the Scandinavian Obesity Surgery Registry (SOReg) between 2010 and 2015 were included in this study. The patients who underwent a bariatric procedure between 2010 and 2014 were used as training data, and those who underwent a bariatric procedure in 2015 were used as test data. Postoperative complications were graded according to the Clavien-Dindo classification, and complications requiring intervention under general anesthesia or resulting in organ failure or death were considered serious. Three supervised deep learning neural networks were applied and compared in our study: multilayer perceptron (MLP), convolutional neural network (CNN), and recurrent neural network (RNN). The synthetic minority oversampling technique (SMOTE) was used to artificially augment the patients with serious complications. The performances of the neural networks were evaluated using accuracy, sensitivity, specificity, Matthews correlation coefficient, and area under the receiver operating characteristic curve.

RESULTS: In total, 37,811 and 6250 patients were used as the training data and test data, with incidence rates of serious complication of 3.2% (1220/37,811) and 3.0% (188/6250), respectively. When trained using the SMOTE data, the MLP appeared to have a desirable performance, with an area under curve (AUC) of 0.84 (95% CI 0.83-0.85). However, its performance was low for the test data, with an AUC of 0.54 (95% CI 0.53-0.55). The performance of CNN was similar to that of MLP. It generated AUCs of 0.79 (95% CI 0.78-0.80) and 0.57 (95% CI 0.59-0.61) for the SMOTE data and test data, respectively. Compared with the MLP and CNN, the RNN showed worse performance, with AUCs of 0.65 (95% CI 0.64-0.66) and 0.55 (95% CI 0.53-0.57) for the SMOTE data and test data, respectively.

CONCLUSIONS: MLP and CNN showed improved, but limited, ability for predicting the postoperative serious complications after bariatric surgery in the Scandinavian Obesity Surgery Registry data. However, the overfitting issue is still apparent and needs to be overcome by incorporating intra- and perioperative information.

Place, publisher, year, edition, pages
JMIR Publications, 2020
Keywords
Bariatric surgery, computational neural networks, deep learning, postoperative complications, projections and predictions
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-81770 (URN)10.2196/15992 (DOI)000531089200004 ()32383681 (PubMedID)
Note

Funding Agency:

Örebro Region County Council  OLL-864441

Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-05-25Bibliographically approved
Rundquist, S., Sachs, M., Eriksson, C., Olén, O., Montgomery, S. & Halfvarson, J. (2020). Effectiveness of anti-TNF vs. vedolizumab as a second biologic in IBD: results from national Swedish registers. Journal of Crohn's & Colitis, 14(Suppl. 1), S317-S318
Open this publication in new window or tab >>Effectiveness of anti-TNF vs. vedolizumab as a second biologic in IBD: results from national Swedish registers
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2020 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no Suppl. 1, p. S317-S318Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2020
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-81139 (URN)10.1093/ecco-jcc/jjz203.456 (DOI)000518803401226 ()
Available from: 2020-04-14 Created: 2020-04-14 Last updated: 2020-04-14Bibliographically approved
Göthlin Eremo, A., Lagergren, K., Othman, L., Montgomery, S., Andersson, G. & Tina, E. (2020). Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer. Scientific Reports, 10(1), Article ID 1451.
Open this publication in new window or tab >>Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer
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2020 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 10, no 1, article id 1451Article in journal (Refereed) Published
Abstract [en]

Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor- positive (ER+) breast cancer tissue. Tamoxifen- treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30-4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45-9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-79955 (URN)10.1038/s41598-020-58323-w (DOI)000528915400031 ()31996744 (PubMedID)2-s2.0-85078689992 (Scopus ID)
Funder
Swedish Cancer Society
Note

Funding Agencies:

Lions Cancer Research fund (Region Uppsala Örebro), Research committee, Region Örebro County  

ALF grants, Region Örebro County 

Available from: 2020-02-19 Created: 2020-02-19 Last updated: 2020-05-18Bibliographically approved
Wireklint, P., Hasselgren, M., Montgomery, S., Lisspers, K., Ställberg, B., Janson, C. & Sundh, J. (2020). Factors associated with knowledge of self-management of worsening asthma in primary care patients: a cross-sectional study. Journal of Asthma, 1-11
Open this publication in new window or tab >>Factors associated with knowledge of self-management of worsening asthma in primary care patients: a cross-sectional study
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2020 (English)In: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, p. 1-11Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Self-management is important for asthma control. We examined associations of patient- and healthcare-related factors with self-reported knowledge of self-management of worsening asthma.

METHOD: Two asthma patient cohorts from 2012 (n = 527) and 2015 (n = 915) were randomly selected from 54 primary health care centers (PHCC) in central Sweden. Data were collected using patient questionnaires and questionnaires to the PHCCs. Logistic regression analyzed associations of relevant variables with knowledge of self-management of worsening asthma.

RESULTS: In total, 63% of patients reported moderate to complete knowledge of self-management procedures. The adjusted OR for moderate to complete knowledge relative to high education level was 1.38 [95% CI 1.03-1.85)]; for physician continuity 2.19 (95% CI 1.62-2.96); for a written action plan, 11.9 (95% CI 6.16-22.9); for Step 2 maintenance treatment, 1.53 (95% CI 0.04-2.24); and 2.07 (95% CI 1.44-2.99) for Step 3. An asthma/COPD nurse visit within the previous 12 months was associated with greater knowledge in women but not in men (p for interaction =0.042). Smoking [OR 0.56 (95% CI 0.34-0.95)], co-morbidities ≥1 [OR 0.68 (95% CI 0.49-0.93)], and self-rated moderate/severe disease [OR 0.68 (95% CI 0.51-0.90)] were associated with low self-management knowledge.

CONCLUSION: Self-reported knowledge of self-management procedures was associated with a higher educational level, physician continuity, a written action plan, advanced treatment and, in women, visiting an asthma/COPD nurse. The results reinforce the importance of implementing guidelines of patient access to a specific physician, a written action plan, and structured education by an asthma/COPD nurse.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Self-management, asthma, asthma/COPD nurse, education level, patient-specific physician, primary care, written action plan
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:oru:diva-81349 (URN)10.1080/02770903.2020.1753209 (DOI)000532277100001 ()32283944 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Asthma and Allergy Association
Note

Funding Agencies:

County councils of the Uppsala-Örebro Health Care region

Bror Hjerpstedts Foundation  

Center for Clinical Research, Dalarna  

Uppsala-Örebro Regional Research Council  

Region Örebro County through ALF research fund 

Available from: 2020-04-29 Created: 2020-04-29 Last updated: 2020-05-29Bibliographically approved
Lindgren, H., Hasselgren, M., Montgomery, S., Lisspers, K., Ställberg, B., Janson, C. & Sundh, J. (2020). Factors associated with well-controlled asthma: A cross-sectional study [Letter to the editor]. Allergy. European Journal of Allergy and Clinical Immunology, 75(1), 208-211
Open this publication in new window or tab >>Factors associated with well-controlled asthma: A cross-sectional study
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2020 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 75, no 1, p. 208-211Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Munksgaard Forlag, 2020
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:oru:diva-75593 (URN)10.1111/all.13976 (DOI)000479801000001 ()31298735 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Asthma and Allergy Association
Note

Funding Agencies:

County councils of the Uppsala-Örebro Health Care region

Bror Hjerpstedts Foundation  

Center for Clinical Research, Dalarna  

Region Örebro County through ALF 

Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-13Bibliographically approved
Batyrbekova, N., Aleman, S., Lybeck, C., Montgomery, S. & Duberg, A.-S. (2020). Hepatitis C virus infection and the temporal trends in the risk of liver cancer: a national register-based cohort study in Sweden. Cancer Epidemiology, Biomarkers and Prevention, 29(1), 63-70
Open this publication in new window or tab >>Hepatitis C virus infection and the temporal trends in the risk of liver cancer: a national register-based cohort study in Sweden
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2020 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 1, p. 63-70Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV-infection between 1990 and 2015.

METHODS: The HCV-cohort (n: 52,853) was compared with a matched non-HCV comparison-cohort (n: 523,649). Both the Cancer (CR) and Death registers (DR) were used for follow-up. The crude and age-standardised PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as hazard ratios (HR) using stratified Cox hazards regression.

RESULTS: There were 1,609 with PLC-diagnosis in the HCV-cohort, the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013, while remaining low and stable in the comparison-cohort. In the HCV-cohort, the age-standardised PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 (95% CI: 1.54, 3.75) in 2000 and 3.31 (2.51, 4.12) in 2014. The highest SIR was 73 (65.9, 79.5) among those infected for 35-40 years; and the highest HR was 65.9 (55.9, 77.6) for men and 62.2 (31.9, 121.1) for women.

CONCLUSIONS: There was a considerable increase in PLC-incidence over time and an extremely high relative risk in the population with HCV-infection for more than 35 years.

IMPACT: The national HCV-associated PLC-incidence should be monitored in future studies to evaluate the effect of DAA-treatment.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-77946 (URN)10.1158/1055-9965.EPI-19-0769 (DOI)000521285100008 ()31719064 (PubMedID)2-s2.0-85077926564 (Scopus ID)
Note

Funding Agencies:

Research ALF grants from Region Örebro County  OLL-683801

Nyckelfonden, Örebro, Sweden  OLL-691511

Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2020-04-07Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6328-5494

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