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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
Wernroth, M.-L., Fall, K., Svennblad, B., Ludvigsson, J. F., Sjölander, A., Almqvist, C. & Fall, T. (2020). Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes: A Nationwide Register-Based Study With Sibling Analysis. Diabetes Care, 43(5), 991-999
Open this publication in new window or tab >>Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes: A Nationwide Register-Based Study With Sibling Analysis
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2020 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, no 5, p. 991-999Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The effect of early life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis.

RESEARCH DESIGN AND METHODS: = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings.

RESULTS: for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00-1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations.

CONCLUSIONS: Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10, most prominently in children delivered by cesarean section.

Place, publisher, year, edition, pages
American Diabetes Association, 2020
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-80480 (URN)10.2337/dc19-1162 (DOI)000528504700010 ()32132008 (PubMedID)2-s2.0-85083841034 (Scopus ID)
Funder
Swedish Research Council, 2015-03477
Note

Funding Agencies:

Vetenskapsrådet (Swedish Research Council) through Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework  340-2013-5867

Uppsala Antibiotic Center 

Available from: 2020-03-09 Created: 2020-03-09 Last updated: 2020-05-06Bibliographically approved
Chen, R., Zhan, Y., Pedersen, N., Fall, K., Valdimarsdóttir, U. A., Hägg, S. & Fang, F. (2020). Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort. Heart, 106(4), 267-272
Open this publication in new window or tab >>Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort
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2020 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 106, no 4, p. 267-272Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association.

DESIGN: Population-based prospective cohort study SETTINGS: Swedish Twin Registry.

PARTICIPANTS: Based on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique.

MAIN OUTCOME MEASURES: Incident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index.

RESULTS: A total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:-0.014, 95% CI: -0.035, 0.007), widowed (β:-0.035, 95% CI: -0.061, -0.010), or living alone (β:-0.033, 95% CI: -0.052, -0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34).

CONCLUSIONS: Living singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2020
Keywords
Cardiac risk factors and prevention, epidemiology, quality and outcomes of care
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-77941 (URN)10.1136/heartjnl-2019-315629 (DOI)000518192600009 ()31727634 (PubMedID)
Note

Funding Agency:

Karolinska Institutet (the Strategic Research Area in Epidemiology)

Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2020-03-20Bibliographically approved
Jerlström, T., Ruoqing, C., Liedberg, F., Andrén, O., Ströck, V., Aljabery, F. A. S., . . . Fall, K. (2020). No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study. World journal of urology, 38(2), 381-388
Open this publication in new window or tab >>No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study
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2020 (English)In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, no 2, p. 381-388Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking.

METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not.

RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81).

CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

Place, publisher, year, edition, pages
Springer, 2020
Keywords
Bladder cancer, Induction chemotherapy, Neoadjuvant chemotherapy, Postoperative complications, Radical cystectomy
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-73968 (URN)10.1007/s00345-019-02770-2 (DOI)000511513400017 ()31020424 (PubMedID)2-s2.0-85064805869 (Scopus ID)
Note

Funding Agencies:

Lions Cancer Research Foundation  

Foundation for Medical Research at Örebro University Hospital, Sweden  

Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2020-03-17Bibliographically approved
Zhu, J., Chen, R., Davidsson, S., Carlsson, J., Messing-Eriksson, A., Fridfeldt, J., . . . Fall, K. (2020). Psychological and physiological impacts of a fast-track diagnostic workup for men with suspected prostate cancer: Preliminary report from a randomized clinical trial [Letter to the editor]. Cancer communications (London, England)
Open this publication in new window or tab >>Psychological and physiological impacts of a fast-track diagnostic workup for men with suspected prostate cancer: Preliminary report from a randomized clinical trial
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2020 (English)In: Cancer communications (London, England), ISSN 2523-3548Article in journal, Letter (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
John Wiley & Sons, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-81198 (URN)10.1002/cac2.12021 (DOI)000525266500001 ()32255568 (PubMedID)
Funder
Swedish Cancer Society, CF2016/795 2018/765
Note

Funding Agency:

Nyckelfonden, Örebro, Sweden

Available from: 2020-04-17 Created: 2020-04-17 Last updated: 2020-04-30Bibliographically approved
Li, Y., Wang, Y., Jiang, J., Valdimarsdóttir, U. A., Fall, K., Fang, F., . . . Zhang, W. (2020). Psychological distress among health professional students during the COVID-19 outbreak. Psychological Medicine, 1-12
Open this publication in new window or tab >>Psychological distress among health professional students during the COVID-19 outbreak
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2020 (English)In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, p. 1-12Article in journal (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
Cambridge University Press, 2020
National Category
Psychology
Identifiers
urn:nbn:se:oru:diva-81843 (URN)10.1017/S0033291720001555 (DOI)32389148 (PubMedID)
Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2020-05-13Bibliographically approved
Zhang, Y., Zhou, C. K., Rencsok, E. M., Fall, K., Lotan, T. L., Loda, M., . . . Ebot, E. M. (2019). A prospective study of intraprostatic inflammation, focal atrophy, and progression to lethal prostate cancer. Cancer Epidemiology, Biomarkers and Prevention, 28(12), 2047-2054
Open this publication in new window or tab >>A prospective study of intraprostatic inflammation, focal atrophy, and progression to lethal prostate cancer
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 12, p. 2047-2054Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance.

METHODS: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up.

RESULTS: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. Eighty-four percent of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR=0.45, 95% CI 0.30 to 0.69 for mild, HR=0.51, 95% CI 0.33 to 0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer.

CONCLUSIONS: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among prostate cancer patients.

IMPACT: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-76639 (URN)10.1158/1055-9965.EPI-19-0713 (DOI)000502588500014 ()31533941 (PubMedID)2-s2.0-85076025800 (Scopus ID)
Note

Funding Agencies:

Cancer Center Support Grants from the NCI  P30 CA006516 P30 CA006973

Emory, Harvard and University of Washington Prostate Cancer Biomarker Center  U01 CA113913   U01 CA167552

Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2020-01-14Bibliographically approved
Kantor, E. D., Udumyan, R., Giovannucci, E. L., Valdimarsdottir, U. A., Signorello, L. B., Montgomery, S. & Fall, K. (2019). Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality [Letter to the editor]. JAMA pediatrics, 173(11), 1095-1097
Open this publication in new window or tab >>Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality
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2019 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 173, no 11, p. 1095-1097Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Biochemistry and Molecular Biology Pediatrics
Identifiers
urn:nbn:se:oru:diva-76166 (URN)10.1001/jamapediatrics.2019.2835 (DOI)000503205800017 ()31479147 (PubMedID)2-s2.0-85071754548 (Scopus ID)
Note

Funding Agencies:

Örebro University  

Economic & Social Research Council (ESRC) RES-596-28-0001ES/JO19119/1

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Cancer Institute (NCI) T32CA009001 P30CA008748

Harvard T. H. Chan School of Public Health 

Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2020-01-14Bibliographically approved
Udumyan, R., Montgomery, S., Fang, F., Valdimarsdóttir, U., Hardardottir, H., Ekbom, A., . . . Fall, K. (2019). Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer. Cancer Epidemiology, Biomarkers and Prevention, 29(1), 119-126
Open this publication in new window or tab >>Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 1, p. 119-126Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Beta-adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for non-small cell lung cancer (NSCLC) patients is contradictory and limited to small hospital-based studies. We therefore aimed to investigate if β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date.

PATIENTS AND METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between beta-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register.

RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with non-use, beta-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [hazard ratio (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific beta-blockers and some histopathological subtypes exist cannot be excluded.

CONCLUSION: In this nationwide cohort of NSCLC patients, beta-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some beta-blockers is less conclusive.

IMPACT: Our results do not indicate that beta-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in NSCLC patients.

Place, publisher, year, edition, pages
Prevention American Association for Cancer Research, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-77618 (URN)10.1158/1055-9965.EPI-19-0710 (DOI)000521285100015 ()31641010 (PubMedID)2-s2.0-85077915694 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2013/650
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2020-05-05Bibliographically approved
Ugge, H., Downer, M. K., Carlsson, J., Bowden, M., Davidsson, S., Mucci, L. A., . . . Andrén, O. (2019). Circulating inflammation markers and prostate cancer. The Prostate, 79(11), 1338-1346
Open this publication in new window or tab >>Circulating inflammation markers and prostate cancer
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2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 11, p. 1338-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population-based case-control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation.

METHODS: Serum samples collected from 235 prostate cancer patients and 198 population-based controls recruited in Örebro County, Sweden, in 1989-1991, were assessed using a multiplex bead-based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers.

RESULTS: Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C-X3-C motif chemokine ligand 1, platelet-derived growth factor subunit B homodimer, interleukin 10, C-C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant.

CONCLUSIONS: In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.

Place, publisher, year, edition, pages
Alan R. Liss Inc., 2019
Keywords
Circulating, cytokines, inflammation, markers, prostate cancer
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-74753 (URN)10.1002/pros.23842 (DOI)000473235500014 ()31212389 (PubMedID)2-s2.0-85068041866 (Scopus ID)
Note

Funding Agency:

Lions Cancerforskningsfond vid Akademiska sjukhuset i Uppsala. (Part of Lions International)

Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-08-09Bibliographically approved
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