To Örebro University

Background and aims: Non-western immigrants to Europe are at high risk for type 2 diabetes (T2D). In this nationwide study including incident cases of T2D, the aim was to compare mortality in first- and second generation immigrants with native Swedes.

Materials and methods: Patients living in Sweden diagnosed with a new-onset pharmacologically treated T2D between 2006 to 2012 were identified through the Swedish Prescription Drug Register. Patients were followed until December 31, 2016 for all-cause mortality (ACM) and until December 31, 2012 for cause-specific mortality (CSM). Analyses were adjusted for age at diagnosis, sex, year of diagnosis, socioeconomy, education, treatment and region. Comparisons were assessed using coxregression analysis.

Results: In total, 169 300 individuals (129 533 (76.3%) native Swedes; 31 988 (18.9%) first-generation immigrants, and 7 799 (4.8%) second-generation immigrants with either one or both parents born outside Sweden) were diagnosed with T2D between 2006 and 2012 and fulfilled inclusion criteria. First-generation immigrants had lower ACM rate [hazard ratio (HR): 0.85, 95% CI 0.82 to 0.89] compared with native Swedes. The mortality was particularly low in persons born in the Middle East [0.45,0.40 to 0.51], Asia [0.56, 0.46 to 0.68], and Africa [0.88. 0.82 to 0.95]. Mortality rates decreased with older age at migration and shorter stay in Sweden, with the lowest rate in those originating from the Middle East living in Sweden <25 years [0.40, 0.34 to 0.46]. First-generation immigrants born in the Middle East (0.43; 0.30-0.62), and Asia (0.38; 0.19- 0.77) had lower cardiovascular disease related mortality rates compared with native Swedes. Middle Eastern immigrants further displayed lower cancer related mortality rate (0.59, 0.42 to 0.84) compared with native Swedes. Second generation immigrants displayed similar survival rates as native Swedes.

Conclusion: Our data indicate that in T2D patients, exposure to the Swedish environment seems to have a larger impact on mortality risk than region of origin. This study indicates protecting mechanisms on mortality related to the non-western environment.

Swedish guidelines recommend cervical screening with primary HPV for women ≥ 30 years of age. The aim of this study was to compare an implemented HPV cervical screening programme in the Region of Örebro County from September 1, 2016, with the former cytology-based screening programme.

The clinical effectiveness by means of number of high-grade squamous intraepithelial lesions (HSILs) and cervical cancer cases detected in histology within 12 months after the screening test, together with cost implications were the main outcomes. Data were retrieved from the Swedish National Cervical Screening Registry between the years 2014-2015 (cytology based screening) and 2017-2018(HPV based screening), including screening information such as invitations and cytology and histology diagnoses.

The detection rate of HSIL + among women ≥ 30 years of age was 1.2 times higher with HPV screening, but data revealed an increase in direct colposcopy referral rate by 54% and a higher percentage of irrelevant findings (≤LSIL). Screening based on HPV for women ≥ 30 has increased yearly cost from 1 to 1.3 million EUR, while increasing the number of HSIL + identified. Two thirds of the total costs are from visits for screening samples in the programme.

HPV screening detected more cases of HSIL + compared to cytology screening among women ≥ 30 although high colposcopy rate, high rate of clinical irrelevant findings and higher costs were shown in the HPV-based screening programme, which implies that alterations in the screening programme in the future are important to consider.

Background: Severe infections in adulthood are associated with subsequent short-term cardiovascular disease. Whether hospital admission for sepsis or pneumonia is associated with persistent increased risk (over a year after infection) is less well established.

Design: The design of this study was as a register-based cohort study.

Methods: Some 236,739 men born between 1952-1956 were followed from conscription assessments in adolescence to 2010. All-cause cardiovascular disease ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n = 3438), was identified through national registers 1970-2010 (at ages 18-58 years).

Results: Sepsis or pneumonia in adulthood (resulting in hospital admission) are associated with increased risk of cardiovascular disease in the years following infection. The risk is highest during the first year after the infection, with an adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the second and 2.12 (1.71-2.62) for the third year after infection. The risk attenuated with time, but remained raised for at least five years after infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in childhood, cardiovascular risk factors and medical history in adolescence. Similar statistically significant associations were found for coronary heart disease and stroke.

Conclusions: Raised risks of cardiovascular disease following hospital admission for sepsis or pneumonia were increased for more than five years after the infection, but with the highest magnitude during the first three years following infection, suggesting a period of vulnerability when health professionals and patients should be aware of the heightened risk for cardiovascular disease.

Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.

Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.

Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).

Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.

OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.

METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.

RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).

CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.

Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.

Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.

Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.

Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.

Background: Depression is associated with coronary heart disease and stroke, but associations with a range of pathologically diverse cardiovascular diseases are not well understood. We examine the risk of 12 cardiovascular diseases according to depression status (history or new onset).

Methods: Cohort study of 1,937,360 adult men and women, free from cardiovascular disease at baseline, using linked UK electronic health records between 1997 and 2010. The exposures were new-onset depression (a new GP diagnosis of depression and/or prescription for antidepressants during a one-year baseline), and history of GP-diagnosed depression before baseline. The primary endpoint was initial presentation of 12 cardiovascular diseases after baseline. We used disease-specific Cox proportional hazards models with multiple imputation adjusting for cardiovascular risk factors (age, sex, socioeconomic status, smoking, blood pressure, diabetes, cholesterol).

Results: Over a median [IQR] 6.9 [2.1-10.5] years of follow-up, 18.9% had a history of depression and 94,432 incident cardiovascular events occurred. After adjustment for cardiovascular risk factors, history of depression was associated with: stable angina (Hazard Ratio = 1.38, 95%CI 1.32-1.45), unstable angina (1.70, 1.60-1.82), myocardial infarction (1.21, 1.16-1.27), unheralded coronary death (1.23, 1.14-1.32), heart failure (1.18, 1.13-1.24), cardiac arrest (1.14, 1.03-1.26), transient ischemic attack (1.31, 1.25-1.38), ischemic stroke (1.26, 1.18-1.34), subarachnoid haemorrhage (1.17, 1.01-1.35), intracerebral haemorrhage (1.30, 1.17-1.45), peripheral arterial disease (1.24, 1.18-1.30), and abdominal aortic aneurysm (1.12,1.01-1.24). New onset depression developed in 2.9% of people, among whom 63,761 cardiovascular events occurred. New onset depression was similarly associated with each of the 12 diseases, with no evidence of stronger associations compared to history of depression. The strength of association between depression and these cardiovascular diseases did not differ between women and men.

Conclusions: Depression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity. Further research is needed in understanding the specific pathophysiology of heart and vascular disease triggered by depression in healthy populations.

BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent.

METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection.

RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH.

CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.

Bakgrund: Randomiserade kontrollerade prövningar har visat effekt av golimumab vid ulcerös kolit men studiedeltagare och förhållanden i kliniska prövningar motsvarar inte alltid svensk klinisk vardag. Syftet med denna studie var att utvärdera säkerhet och effekt av behandling med golimumab vid ulcerös kolit under svenska förhållanden.

Metod: Detta är en prospektiv kohortstudie med inklusion av patienter från svenska sjukhus. Patienter med måttlig till svår aktiv ulcerös kolit, definierad som endoskopiskt Mayo score ≥2 och som påbörjade golimumab fr.o.m. 1/6-2014 inkluderades efter att informerat samtycke inhämtats. Kliniska karakteristika, behandling, klinisk-, biokemisk- och endoskopisk aktivitet liksom skattning av livskvalité samlades in vid inklusion samt prospektivt med hjälp av ett elektroniskt studieformulär, integrerat i svenska kvalitetsregistret för IBD (SWIBREG). Primärt effektmått var klinisk effekt vid 3 samt 12 månader (definierat som minskat Mayo score med ≥3 poäng eller 30 % från inklusion), samt klinisk remission (definierad som Mayo score ≤ 2 utan några enskilda poäng >1). Kontinuerliga data presenteras som median och kvartilavstånd. För statistisk jämförelse mellan inklusion och uppföljning användes Wilcoxon-signed rank test. Data från induktionsbehandling samt 3-månadersuppföljning presenteras här.

Resultat: 50 patienter inkluderades t.o.m. 15/9-2017. Vid studiestart var 24/50 (48 %) samtidigt behandlade med immunmodulerare, 16/50 (32 %) med perorala kortikosteroider samt 27/50 (54 %) med 5-ASA. Totalt hade 35/50 (70 %) tidigare fått behandling med minst en TNF-hämmare (tabell 1). Efter 12 veckor hade 37/50 (74 %), fortfarande behandling med golimumab. Av de patienter som fortsatte med golimumab till vecka 12 var 8 (22 %) i klinisk remission och 13 (35 %) uppvisade klinisk respons. Totalt Mayo score minskade i median från 7 (6-10) vid inklusion till 5 (1-8) vid 12 veckor (p<0.01). Fekalt calprotektin minskade från 710 (275-1850) µg/g till 390 (45-870) µg/g (p=0.02). Livskvalitet hos golimumab-behandlade patienter förbättrades, uppmätt som en signifikant minskning av poäng på short health scale (p=0.04).

Slutsats: Golimumab-behandlade patienter i Sverige utgör en svårbehandlad grupp. Trots det kan förbättring av kliniska parametrar, inflammatorisk aktivitet och upplevd livskvalité uppnås redan efter 12 veckors golimumab-behandling.

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).

Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).

Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.

Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Objectives: Systematic review and meta-analysis on the diagnostic accuracy of temporal artery thermometers (TAT).

Design: Systematic review and meta-analysis. The index test consisted of temperature measurement with TAT. The reference test consisted of an estimation of core temperature.

Participants: Clinical patients as well as healthy participants, with or without fever.

Interventions: Literature search in PubMed, Embase, Cinahl and Web of Science. Three reviewers selected articles for full-text reading after which a further selection was made. Risk of bias was assessed with QUADAS-2. Pooled difference and limits of agreement (LoA) were estimated with an inverse variance weighted approach. Subgroup and sensitivity analyses were performed. Sensitivity and specificity were estimated using hierarchical models. Quality of evidence was assessed according to the GRADE system.

Primary and secondary outcome measures: The primary outcome was measurement accuracy expressed as mean difference ±95% LoA. A secondary outcome was sensitivity and specificity to detect fever. If tympanic thermometers were assessed in the same population as TAT, these results were recorded as well.

Results: 37 articles comprising 5026 participants were selected. Pooled difference was -0.19°C (95% LoA -1.16 to 0.77°C), with moderate quality of evidence. Pooled sensitivity was 0.72 (95% CI 0.61 to 0.81) with a specificity of 0.94 (95% CI 0.87 to 0.97). The subgroup analysis revealed a trend towards underestimation of the temperature for febrile patients. There was a large heterogeneity among included studies with wide LoA which reduced the quality of evidence.

Conclusions: TAT is not sufficiently accurate to replace one of the reference methods such as rectal, bladder or more invasive temperature measurement methods. The results are, however, similar to those with tympanic thermometers, both in our meta-analysis and when compared with others. Thus, it seems that TAT could replace tympanic thermometers with the caveat that both methods are inaccurate.

Trial registration number: CRD42014008832.

Background and purpose: Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated.

Methods: A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination.

Results and conclusions: Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P=0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P=0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS.

OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune liver disease that may progress into liver cirrhosis. Ursodeoxycholic acid (UDCA) is known to prevent or delay the disease progression, but little is known about work incapacity in PBC patients. We aimed to compare clinical outcomes (transplantation-free survival; cirrhosis development) and sick leave in patients with PBC with and without UDCA therapy.

METHODS: The medical records of 526 patients with PBC diagnosed from 2004 to 2016 were reviewed retrospectively. Sick leave data retrieved from the Swedish Social Insurance Agency were analysed for a sub-cohort of patients and matched controls. Cox regression was used for analysis of clinical outcomes. Logistic and conditional logistic regressions were used for sick leave analysis.

RESULTS: A total of 10.6% of patients died and 3.4% received liver transplantation over a median follow-up time of 5.7 years. UDCA-untreated patients (HR 3.62 (95%CI 2.02-6.49)) and UDCA non-responders (HR 3.78 (95% CI 1.87-7.66)) had higher mortality or transplantation rates than UDCA responders. Patients with PBC had higher odds of sick leave (OR 2.50; 95% CI 1.69-3.70) than matched controls. Untreated patients were more likely to be on sick leave (OR 3.22; 95% CI 1.12-9.25) two years after diagnosis than UDCA responders.

CONCLUSION: Both untreated patients and UDCA non-responders had lower liver transplantation-free survival rates than UDCA responders. Patients with PBC were more likely to be on sick leave compared to matched controls from the general population.

It is unclear whether psychological resilience to stress in adolescence represents a persistent characteristic relevant to the subsequent risk for depression and anxiety in later adulthood. We aimed to test whether low psychological stress resilience assessed in adolescence is associated with an increased risk of receiving medication for depression and anxiety in middle age. We utilized Swedish register-based cohort study. Men born between 1952 and 1956 (n = 175,699), who underwent compulsory assessment for military conscription in late adolescence were followed to examine subsequent risk of pharmaceutically-treated depression and anxiety in middle age, from 2006 to 2009 corresponding to ages between 50 and 58 years, using Cox regression. The associations of stress resilience with prescription of antidepressant and anxiolytics medication through potential mediating factors cognitive and physical function and adult socioeconomic factors were calculated. Low stress resilience was associated with elevated risks for antidepressant (hazard ratio (HR):1.5 (95% CI 1.4 1.6)) and anxiolytics (HR:2.4 (CI 2.0 2.7)) medication. Adjustment for measures of childhood living circumstances attenuated the associations somewhat. Around a third of association with low stress resilience, and a half of that with moderate resilience, was mediated through cognitive and physical function in adolescence and adult socioeconomic factors. The magnitude of the inverse association of higher cognitive function with antidepressant medication was eliminated among those with low stress resilience. These results indicate that low stress resilience in adolescence is associated with an increased risk for antidepressant and anxiolytics medication over 30 years later, in part mediated through developmental factors in adolescence and socioeconomic circumstances in adulthood, and low stress resilience can diminish or eliminate the inverse association of higher cognitive function with antidepressant medication.

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

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

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

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

Background: Stress resilience is recognised as a determinant of both psychiatric and somatic health, but the potential link between stress resilience and cancer development has not been explored.

Methods: In this nationwide cohort study, we examined the association between stress resilience in adolescence and subsequent cancer risk. We identified a cohort of 284 257 Swedish men, born 1952-1956, who underwent compulsory military enlistment examinations including measures of psychological stress resilience (median age 18 years). The resulting score was categorised as low, moderate and high stress resilience. Individuals diagnosed with cancer during the follow-up time were identified through data linkage to the Swedish Cancer Register.

Results: Lowest stress resilience, compared with the highest, was associated with increased risks of liver (HR: 4.73, 95% CI 2.73 to 8.19) and lung (HR: 2.75, 95% CI 2.02 to 3.74) cancer after adjusting for markers of socioeconomic circumstances in childhood (p for trend <0.001 for both cancer types). Further adjustment for cognitive and physical fitness at conscription assessment had a marginal influence. In contrast, men with low stress resilience had a decreased risk of being diagnosed with prostate cancer (HR: 0.65, 95% CI 0.56 to 0.76) and malignant melanoma (HR: 0.65, 95% CI 0.55 to 0.76).

Conclusion: We conclude that adolescent stress resilience, plausibly by influencing behavioural choices and social patterns, constitutes an important determinant of adult cancer occurrence. Increased awareness of longterm consequences in susceptible individuals may help direct future efforts to reduce cancer burden in adults.

Background Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods A total of 2134 patients with incident GD and 21261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to ten age, sex- and county-matched controls per patient were selected from databases from The National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and 95% confidence intervals. Results There were no significant differences in fracture rates between GD and controls but after adjustment for co-morbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 (1.05-7.64). The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

PURPOSE: Time management skills are essential for handling daily life in a modern society. People with ADHD, Autism spectrum disorder or mental disorders may have affected time management, which for example might lead to poor occupational balance, low self-efficacy and difficulites to maintain family and working life. Let’s Get Organized’(LGO) is a manual-based group intervention to improve time management skills. The aim of this trial was to evaluate the efficiency of the Swedish version of LGO (LGO-S) compared to treatment as usual (individual occupational therapy) to improve time management for adults with impaired time management skills due to neurodevelopmental or mental disorders.

DESIGN: Multi-center two-armed open parallel randomized controlled trail (RCT). Participants (n=88) from nine out-patient psychiatric or habilitation care units were randomized into 1) Let’s Get Organized (LGO-S) and 2) individual occupational therapy (treatment as usual).

METHOD: Both groups received intervention for 10 weeks. Data was collected pre-, post- and three months post intervention. Primary outcome measure was self-assessed time management skills. Secondary outcome measures were self assessed planning and organisational skills, regulation of emotions, satisfaction with daily occupations and self-efficacy.

RESULTS: Both LGO and Individual occupational therapy showed statistically significant improvements in time management skills after intervention (p<0.001 in both groups). The results were maintained at the three month follow-up. There were no statistically significant differences between groups. Analyzes of secondary outcomes are ongoing and will be presented at the conference.

CONCLUSION: Both LGO and individual occupational therapy had a positive effect on the participants’ time management skills. Conclusions about secondary outcomes and possible correlations will be presented at the conference.

BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.

METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.

RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.

CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

BACKGROUND: Psychosocial stress may influence peptic ulcer disease (PUD) risk, but it can be difficult to identify reliably whether stressful exposures pre-dated disease. The association of stress resilience (susceptibility to stress) with subsequent PUD risk has been incompletely investigated.

AIM: To assess if stress resilience in adolescence is associated with subsequent PUD risk.

METHODS: The participants comprised of 233 093 men resident in Sweden, born 1952-1956 and assessed for compulsory military conscription during 1969-1976, with data provided by national Swedish registers. Stress resilience was evaluated through semi-structured interviews by a certified psychologist. Cox regression assessed the association between stress resilience in adolescence and the risk of PUD from 1985 to 2009, between ages 28 and 57 years, with adjustment for parental socioeconomic index, household crowding and number of siblings in childhood, as well as cognitive function and erythrocyte sedimentation rate in adolescence.

RESULTS: In total, 2259 first PUD diagnoses were identified. Lower stress resilience in adolescence is associated with a higher risk of PUD in subsequent adulthood: compared with high resilience, the adjusted hazard ratios (and 95% CI) are 1.84 (1.61-2.10) and 1.23 (1.09-1.38) for low and moderate stress resilience, respectively.

CONCLUSION: Stress may be implicated in the aetiology of PUD and low stress resilience is a marker of risk.

Background : Number of older siblings is associated with lower cognitive function, possibly as marker of material disadvantage. Sex differences may signal an influence of inter-sibling interactions.

Methods: The study used a national Swedish register-based cohort of men (n=644,603), born between 1970 and 1992 who undertook military conscription assessments in adolescence that included cognitive function measured on a normally-distributed scale of 1-9. Associations with siblings were investigated using linear regression.

Results: After adjustment for numbers of younger siblings, year of conscription assessment, age/year of birth, sex, European socioeconomic classification for parents and maternal age at delivery; the regression coefficients (and 95% confidence intervals) for cognitive function are -0.26 (-0.27, -0.25), -0.42 (-0.44, -0.40), and -0.72 (-0.76, -0.67) for one, two and three or more male older siblings, respectively, compared with none; and -0.22 (-0.23, -0.21), -0.39 (-.41, -0.37), -0.62 (-0.67, -0.58) for one two and three or more female older siblings, respectively, compared with none. A larger number of younger siblings is not associated with lower cognitive function in the adjusted model.

Conclusions: Family size is associated with cognitive function: older male siblings may have greater implications than females due to their demands on familial resources or through inter-sibling interactions.

The aim was to investigate whether older siblings are associated with development of stress resilience in adolescence and if there are differences by sex of siblings. The study used a Swedish register-based cohort of men (n=664 603) born between 1970 and 1992 who undertook military conscription assessments in adolescence that included a measure of stress resilience: associations were assessed using multinomial logistic regression. Adjusted relative risk ratios (95% confidence intervals) for low stress resilience (n=136 746) compared with high (n=142 581) are 1.33 (1.30, 1.35), 1.65 (1.59, 1.71) and 2.36 (2.18, 2.54) for one, two and three or more male older siblings, compared with none. Equivalent values for female older siblings do not have overlapping confidence intervals with males and are 1.19 (1.17, 1.21), 1.46 (1.40, 1.51) and 1.87 (1.73, 2.03). When the individual male and female siblings are compared directly (one male sibling compared with one female sibling, etc.) and after adjustment, including for cognitive function, there is a statistically significant (p<0.005) greater risk for low stress resilience associated with male siblings. Older male siblings may have greater adverse implications for psychological development, perhaps due to greater demands on familial resources or inter-sibling interactions.

BACKGROUND: To evaluate the association of acne in late adolescence with the risk for subsequent malignant melanoma (MM) in men.

METHODS: Swedish register-based cohort study of 242,096 males born between 1952 and 1956, who took part in compulsory assessments for Swedish military conscription in late adolescence between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December 31, 2009. Covariates included measures of childhood circumstances and information from adolescence on presence of acne, physical fitness, cognitive function, body mass index (BMI), and a summary of diagnoses. Cox regression was used for the analysis.

RESULTS: In total 1,058 men were diagnosed with MM. Acne was not associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers, and men who lived in northern Sweden, had lower physical fitness, or lower cognitive function had a lower risk of MM. Overweight and obesity was associated with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71).

CONCLUSIONS: Acne in late adolescence is unlikely to represent a raised risk for subsequent MM in men. Overweight or obesity was identified as a raised risk for MM, possibly due to the associated increased skin surface area.

Oxidative stress and antioxidant deficiency play a pivotal role in initiation, development, and outcomes of cardiovascular disease. Pharmacokinetic parameters as well as the impact of highly bioavailable lycopene on cardiovascular variables, markers of inflammation and oxidation were investigated during a 30-day clinical trial in patients with coronary vascular disease. The patients were randomized into two major groups and were supplemented with a single 7mg daily dose of lycopene ingested either in the form of lactolycopene (68 patients) or in the form of lycosome-formulated GA lycopene (74 patients). The endpoints included cardiovascular function parameters, serum lipids, and four markers of oxidative stress and inflammation. Ingestion of lycosome-formulated lycopene increased serum lycopene levels by 2.9- and 4.3-fold, respectively, after 2 and 4weeks of the trial, whereas supplementation with lactolycopene upregulated serum lycopene by half-fold only after 4weeks of ingestion. Lycosome formulation of lycopene resulted by the end of the trial in a threefold reduction in Chlamydia pneumoniae IgG and reduction to the same degree of the inflammatory oxidative damage marker. The decrease in oxidized LDL caused by lycosome-formulated lycopene was fivefold. Moreover, supplementation with lycosome-formulated lycopene was accompanied by a significant increase in tissue oxygenation and flow-mediated dilation by the end of the observational period. In contrast, lactolycopene did not cause any significant changes in the parameters studied. Therefore, enhanced bioavailability of lycopene promotes its antioxidant and anti-inflammatory functions and endorses a positive effect of lycopene on cardiovascular system.

Introduction Previous research has shown that nursing home applicants had negative experiences of living and receiving care in their ordinary housing due to several factors, such as difficulties in everyday activities and being depressed. However, whether these experiences stand solely for nursing home applicants, or are common in an older population in general needs to be investigated.

Aim of this study was to compare nursing home applicants with matched older adults with respect to difficulties in everyday life, life satisfaction and depressive mood.

Methods Using a case-control design, 34 participants (17 in each group) were compared using Wilcoxon signed rank test for continuous variables and McNemar test for binary variables. The magnitude of associations was explored using conditional logistic regression.

Results Nursing home applicants experienced more difficulties in daily life and were more depressed than their matched peers, and this difference between groups was significant. To experience several difficulties in everyday life and being depressed increased the odds for a nursing home application.

Conclusions As aging in place is the societal norm, older adults with increased likelihood of nursing home applications need to be identified and catered for in an early stage, to prevent nursing home admission.

Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.

Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.

Results: Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model.

Conclusions: Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.

Background: Although acute onset kidney complications associated with severe infections including pneumonia are well characterized, little is known about possible subsequent delayed risk of chronic kidney disease (CKD).

Patients and methods: Associations between hospital admission with pneumonia in adulthood and raised risks of subsequent CKD were evaluated in a cohort of all male residents in Sweden born from 1952 to 1956 (n=284,198) who attended mandatory military conscription examinations in late adolescence (n=264,951) and were followed up through 2009. CKD and pneumonia were identified using Swedish national registers, and their associations were evaluated using Cox regression. Excluding the first year, the subsequent period was divided into <= 5, > 5-<= 15, and > 15 years after hospital admission with pneumonia. Follow-up ended on the date of first incident diagnosis of kidney disease, death, emigration, or December 31, 2009, whichever occurred first.

Results: During a median follow-up of 36.7 (interquartile range 35.3-37.9) years from late adolescence, 5,822 men had an inpatient pneumonia diagnosis without contemporaneous kidney disease. Among exposed men, 136 (2.3%) were later diagnosed with CKD compared with 2,749 (1.2%) of the unexposed. The adjusted hazard ratio for CKD in the first year after the first episode of pneumonia was 14.55 (95% confidence interval, 10.41-20.32), identifying early onset kidney complications and possibly pre-existing undiagnosed CKD. Starting follow-up 1 year after pneumonia to reduce the potential influence of surveillance bias and the risk of reverse causation, the adjusted hazard ratio for CKD in the first 5 years of follow-up was 5.20 (95% confidence interval, 3.91-6.93) and then attenuated with increasing time.

Conclusion: Pneumonia among inpatients is associated with a persistently increased risk for subsequent CKD, with the highest risk during the years immediately after pneumonia. Health care professionals should be aware of this period of heightened risk to facilitate early diagnosis and secondary preventive interventions.

Background: Identification of predictors of end-stage renal disease (ESRD) in adolescence could provide intervention targets and improve understanding of the cause.

Study Design: Register-based nested case-control study.

Setting & Participants: A cohort of all Swedish male residents born from 1952 through 1956 who attended mandatory military conscription examinations in late adolescence was used to identify 534 cases and 5,127 controls matched by birth year, county, and vital status.

Predictor: Erythrocyte sedimentation rate (ESR), proteinuria, blood pressure, and body mass index (BMI) in late adolescence.

Outcomes: ESRD (defined here as dialysis therapy, kidney transplantation, surgical procedures creating long-term access for dialysis therapy, or chronic kidney disease stage 5) from 1985 through 2009.

Measurements: Physical working capacity and cognitive function score in late adolescence. Head of household's occupation and household crowding measured as person-per-room ratio from the 1960 census when participants were children.

Results: Proteinuria is associated notably with future ESRD, with an adjusted OR of 7.72 (95% CI, 3.94-15.14; P < 0.001) for trace or positive dipstick findings. ESR has a dose-dependent association with ESRD with an adjusted OR of 2.07 (95% CI, 1.14-3.75; P = 0.02) for ESR > 15 mm/h. Hypertension is associated strongly with future ESRD with an OR of 3.97 (95% CI, 2.08-7.59; P < 0.001) for grade 2 hypertension and higher. Elevated BMI is associated statistically significantly with increased ESRD risk with an OR of 3.53 (95% CI, 2.04-6.11; P < 0.001) for BMI >= 30 compared with 18.5-<25kg/m(2).

Limitations: The study was limited to men, with no initial estimation of glomerular filtration rate, and information on smoking was unavailable.

Conclusions: ESR, proteinuria, BMI, and blood pressure in late adolescence are independent predictors of ESRD in middle-aged men. This highlights the long natural history and importance of adopting a life-course approach when considering the cause of chronic kidney disease. (C) 2014 by the National Kidney Foundation, Inc.

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH.

METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence.

CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

Accumulating evidence suggests that chronic stress may influence tumour biology through activation of neuroendocrine pathways and thus impair survival. However, measuring stressful exposures and their influence on health is challenging, partly due to substantial inter-individual variation in stress susceptibility. The thesis aimed to explore whether stress resilience and use of β-adrenergic receptor blockers, which are implicated in regulation of neuroendocrine stress response pathways, are linked to survival after a primary cancer diagnosis using data from Swedish national registers. In a cohort of male cancer patients born during 1952-1956 who had their stress resilience assessed during a mandatory conscription examination in late adolescence, low compared with high stress resilience was associated with a higher overall mortality rate. Statistically significant reductions in survival were observed among men with carcinomas of the oropharynx, prostate, upper respiratory tract, and Hodgkin’s lymphoma. In a cohort of patients diagnosed with pancreatic adenocarcinoma during 2006-2009, β-blocker users had a lower pancreatic cancer mortality rate than non-users, particularly among patients without distant metastases at diagnosis. In a cohort of patients diagnosed with non-small cell lung cancer during 2006-2014, there was no clear association between β-blocker use and lung cancer survival, but we cannot exclude the possibility of associations in some sub-groups defined by histology, stage and β-blocker types. In a cohort of patients diagnosed with hepatocellular carcinoma during 2006-2014, β-blocker use was associated with lower liver cancer mortality, particularly among patients with localised disease. A higher-magnitude inverse association was observed for non-selective β-blocker use. In conclusion, greater stress resilience and β-blocker use are associated with improved survival among patients with some cancer types, and this may be explained by a variety of pathways.

Background: Recent observational studies linked beta-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of beta-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of beta-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from beta-blockade therapy. We thus aimed to explore the possible association between beta-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer.

Material and methods: Patients diagnosed during 2006-2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of beta-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported.

Results: Overall, beta-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81-0.96)]. Especially use of nonselective beta-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50-0.86)] and use of other antihypertensive medications [0.72 (0.54-0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18-0.68)]. A lower-magnitude inverse association was observed for selective beta-blocker use [0.91 (0.83-0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70-0.95)] and lipophilic [0.91 (0.83-1.00)] beta-blocker use.

Conclusion: beta-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

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.