To Örebro University

BACKGROUND: Dietary patterns influencing systemic levels of inflammation have been proposed and investigated as possible determinants of cancer risk. We evaluated the association between the anti-inflammatory potential of diet and the risk of bladder cancer (BC).

METHODS: The Anti-Inflammatory Diet Index (AIDI), composed of 16 food groups (11 anti- and 5 pro-inflammatory), was used to score dietary patterns in N=79,292 individuals derived from the Cohort of Swedish Men (COSM, established in 1997) and the Swedish Mammography Cohort (SMC, established in 1987). Dietary information was collected in 1997 and 2009; repeated-measure analyses used a cumulative-average AIDI. Incident BC cases were identified from the Swedish Cancer Register using ICD-10 code C67, and baseline study questionnaire was used to assess covariates. We estimated multivariable hazard ratios across AIDI quartiles using Cox models.

RESULTS: After a 22-year follow-up, 1,165 individuals were diagnosed with BC, of whom 249 had non-muscle invasive (NMI) BC, 201 muscle invasive (MI) BC and 715 unknown stage. In repeated-measures analyses, the highest anti-inflammatory quartile (Q4) was associated with lower BC risk compared with the lowest quartile (Q1) (HR 0.74, 95% CI 0.61-0.89). Stratifying for tumour stage, there was a clear association between AIDI-score and MIBC (HR 0.35, 95% CI 0.22-0.57), but not for NMIBC (HR 0.86, 95% CI 0.57-1.28).

CONCLUSIONS: An anti-inflammatory dietary pattern was associated with lower BC risk, with the clearest association for MIBC. IMPACT: These findings support the role of dietary inflammation in BC aetiology and suggest that promoting anti-inflammatory dietary patterns could contribute to cancer prevention strategies.

BACKGROUND: Clostridioides difficile infections (CDIs) are associated with antibiotic use, although the link with other drugs remains underexplored.

OBJECTIVES: To investigate the association between antibiotic and non-antibiotic drugs with microbiome-modulating activity on new occurrences of CDI.

DESIGN: We conducted a Swedish population-based case-control study from 2006 to 2019 including 42 921 cases matched with 355 159 population controls on age and sex, obtained from multiple linked Swedish registries. The effect of antibiotic and non-antibiotic use within 30 days from the index date on CDI occurrence was estimated using multivariable conditional logistic regression additionally with a lasso penalty. Models were adjusted for age and sex by design and for Charlson Comorbidity Index and concomitant drug use, providing adjusted ORs (aORs) with 95% CIs.

RESULTS: Antibiotics with the greatest CDI risk were lincosamides (aOR=31.4, 95% CI 27.9 to 35.3), combinations of penicillins (aOR=19.8, 95% CI 15.9 to 24.5), sulfonamides and trimethoprim, and cephalosporins, though no association for tetracyclines. Among non-antibiotic drugs, we found decreased risks of CDI for lipid-modifiers (aOR=0.8, 95% CI 0.8 to 0.8) and aspirin (aOR=0.8, 95% CI 0.7 to 0.8) and increased risks for antidiarrhoeals (aOR=7.3, 95% CI 6.8 to 7.8), corticosteroids (aOR=2.4, 95% CI 2.3 to 2.5), proton-pump inhibitors (PPIs) (aOR=1.8, 95% CI 1.7 to 1.8), nervous system drugs, constipation drugs, histamine H2-receptor antagonists, antidepressants, and beta blockers, but no significant risk for non-steroidal anti-inflammatory drugs.

CONCLUSIONS: We found varying effects of antibiotics on CDI, providing evidence for ongoing efforts in prudent prescribing decisions and antimicrobial stewardship. We confirmed PPI as a main risk factor for CDI and provided new evidence for other non-antibiotic drugs as potentially important risk factors considering their high prescription prevalence.

Introduction & Objectives: The diagnostic workup for suspected prostate cancer is often emotionally distressing and may negatively affect patients’ well-being. Considerable variability exists in waiting times across diagnostic pathways, yet evidence on how such delays influence psychological distress is limited. Objective: To assess whether a fast-track diagnostic workup reduces psychological and physiological stress among men with suspected prostate cancer.

Materials & Methods: In this randomized clinical trial, 304 men referred for suspected prostate cancer at the Urology Department, Örebro University Hospital (Sweden), were randomized to either a fast-track diagnostic workup—aiming for the shortest possible waiting time—or usual care. Primary outcomes were patient-reported symptoms of distress (anxiety, depression, perceived stress, and sleep disruption); secondary outcomes included physiological stress markers, such as diurnal salivary cortisol. Data were collected from randomization to 12 months post-enrollment.

Results: Men in the fast-track group had a significantly shorter waiting time to their first consultation (median 7 days) compared with the usual care group (median 35 days). During the first six months, participants in the fast-track arm reported lower levels of distress, anxiety, and perceived stress, and improved sleep quality. Among those undergoing prostate biopsy, the strongest intervention effect was seen one to four weeks post-procedure. For men subsequently diagnosed with prostate cancer, the effect was most pronounced one week after biopsy. Differences between groups were no longer evident at 12 months. Diurnal cortisol profiles indicated a more favorable stress pattern in th efast-track group, especially during the period surrounding diagnostic disclosure.

Conclusions: A fast-track diagnostic workup for suspected prostate cancer substantially reduces psychological and physiological stress during the diagnostic phase. These findings support the implementation of accelerated diagnostic pathways in urological practice to improve patient experience and potentially reduce stress-related health risks.

Background and Aims: Informal caregiving has increased over recent decades. Caregivers may face an increased risk of accidental falls because of care tasks or their consequences, such as fatigue. However, this association has not been investigated. Therefore, we aimed to examine whether giving personal care to someone at home increases fall risk.

Methods: Using longitudinal repeated measures for adults aged over 50 years in 17 European countries, with biennial data collection in 2004-2017 (N = 51,132), we compared periods of caregiving to non-caregiving for falls (outcome) using fixed-effects logistic models, estimating odds ratios (OR) with 95% confidence intervals (95% CI) while controlling for measured time-varying variables as well as unmeasured time-invariant confounders. To shed light on mechanisms, we tested effect modification by sociodemographic characteristics, and examined whether fatigue, sleep problems, lower concentration, and changes in behaviour mediate the association.

Results: Compared with the period of not giving care, the period of providing care was associated with higher fall risk (OR 1.19 [95% CI 1.05-1.35]). This association differed by baseline household income (below or above median). In higher-income households, there was no statistically significant difference in fall risk between the period giving and not giving care (OR 1.07 [95% CI 0.90, 1.26]). In contrast, in lower-income households, the caregiving period was associated with higher fall risk (OR 1.36 [95% CI 1.14-1.63]), which was equivalent to 29% (95% CI 12-46) increased probability of falls in caregiving periods. Fatigue, sleep problems, lower concentration, and behavioural changes jointly mediated 12% of the effect; thus, most of the effect of caregiving on falls is a direct effect.

Conclusion: There was an increased fall risk among caregivers who provide personal care at home in lower-income households. Fatigue and other consequences of caregiving mediated only small effects. Other factors, such as lack of equipment and living space, may relate to mechanisms.

There is evidence that persistent dysregulation of the immune system caused by SARS-CoV-2 infection may increase susceptibility to other infections. Here, we assessed whether it is associated with subsequent diagnoses of infectious mononucleosis due to Epstein-Barr virus (EBV-IM). Residents of Sweden aged 3-100 years without a prior diagnosis of EBV-IM were followed between January 1, 2020, and November 30, 2022, comprising a total of 9 978 860 participants. Individuals were categorized into those without a COVID-19 diagnosis, those with a positive SARS-CoV-2 polymerase chain reaction (PCR) test only - less severe exposure, and those admitted to hospital with COVID-19 - more severe exposure. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the association between the exposure, modeled as a time-varying covariate, and EBV-IM occurrence. EBV-IM rates per 100 000 person-years and 95% CIs were 4.6 (4.4-4.9) for individuals not diagnosed with COVID-19, 7.8 (6.9-8.9) for those with a positive SARS-CoV-2 test only, and 10.5 (6.2-17.6) for patients admitted to hospital with COVID-19. HR and 95% CI were 1.61 (1.39-1.88) for people with a positive PCR test only and 5.71 (3.33-9.79) for those admitted to hospital with COVID-19 compared with people without a COVID-19 diagnosis, after adjustment for birth year, sex, Swedish healthcare region, region of birth, and Charlson comorbidity index. SARS-CoV-2 infection was associated with a subsequent raised risk of EBV-IM, including among those with less severe acute infection, signaling immune perturbation and the possibility of further delayed sequelae linked with EBV-IM.

Introduction & Objectives: Tobacco smoking and occupational exposure to carcinogens constitute well-established risk factors for bladder cancer (BC), while limited evidence suggest a possible effect of dietary factors and inflammation on BC risk. Dietary patterns with impact on systemic levels of inflammation have further been proposed and investigated as possible determinants of cancer risk. In this cohort study, we evaluated the association between the anti-inflammatory potential of diet and the risk of BC.

Materials & Methods: Using the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research (SIMPLER), we identified a study population of N=79,292 men and women derived from the two original cohorts Cohort of Swedish Men (COSM, established in 1997) and Swedish Mammography Cohort (SMC, established in 1987). We used a 96-item food frequency questionnaire (FFQ), completed at baseline in 1997 and repeated in 2009, to calculate the Anti-Inflammatory Diet Index (AIDI) for all participants. AIDI is a previously developed, empirically derived composite measure of dietary anti-inflammatory potential, based on the food groups previously found to have the strongest association with levels of systemic inflammation. The index comprises 16 food groups: 11 with proposed anti-inflammatory and 5 with proposed pro-inflammatory potential. We used ICD-10 code C67 to identify incident BC cases op to year 2020 in the Swedish National Cancer Register, and we used baseline study questionnaire to assess covariates, including smoking status and socioeconomic measures. We further used Cox proportional hazards regression models to estimate unadjusted and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between quartiles of AIDI in the population and later BC diagnosis – overall as well as with outcome separated into non-muscle invasive (NMIBC: Ta or T1 or CIS and N0, M0) and muscle invasive (MIBC: ≤T2 or N1 or M1) BC for cases occurring after year 2004.

Results: During follow-up until 2020, 1165 BC cases occurred, of which 249 were non-muscle invasive, 201 muscle invasive and 715 of unknown stage. Overall, we observed an inverse association between the highest quartile of AIDI (Q4 vs. Q1, representing most anti-inflammatory diet compared to most pro-inflammatory) and later BC diagnosis (multivariable-adjusted HR 0.74, 95% CI 0.61-0.89, p-trend: 0.01). When separating outcome by stage, we observed an association for MIBC (HR 0.35, 95% CI 0.22-0.57), but not for NMIBC (HR 0.86, 95% CI 0.57-1.28).

Conclusions: We observed an inverse association between a measure of dietary anti-inflammatory potential and BC risk, particularly the risk of MIBC. Our observations support a possible implication of the inflammatory potential of diet in BC development and the more pronounced association observed for MIBC may hint at a true biological association.

INTRODUCTION: A diet rich in fruits, vegetables, coffee, and tea, limited red meat, and moderate alcohol intake may reduce the risk of renal cell carcinoma (RCC). The anti-inflammatory potential of diet has been proposed as a mechanism influencing cancer risk. This study assessed the association between an anti-inflammatory diet and RCC risk.

METHODOLOGY: Data from two Swedish cohorts, the Swedish-Mammography-Cohort and the Cohort-of-Swedish-Men, were analysed. Dietary habits were assessed using a 96-item food frequency questionnaire. The Anti-Inflammatory Diet Index (AIDI), composed of 16 food groups (11 anti-inflammatory and 5 pro-inflammatory), was used to score dietary patterns. RCC cases were identified from the Swedish Cancer Register using ICD-10 codes, and Cox proportional hazards models were used to estimate hazard ratios based on AIDI quartiles.

RESULTS: Among 71,421 participants, 431 RCC cases were identified during a 19.7-year follow-up. Higher AIDI scores were associated with a lower RCC risk (HR for Q4 vs. Q1: 0.68, CI: 0.52-0.89). In sex-stratified analyses (p-for heterogeneity = 0.006), the association was stronger in among women (HR: 0.47, CI: 0.30-0.75) but less clear in among men (HR: 0.83, CI: 0.63-1.24).

CONCLUSION: These data suggest that adherence to an anti-inflammatory diet may confer a reduced risk for RCC, especially among women.

AIMS/HYPOTHESIS: The potential impact of childhood bereavement-a severe psychological stressor-on childhood type 1 diabetes development remains unclear. Here, we aimed to bridge this knowledge gap and assess whether bereavement characteristics influenced any impact.

METHODS: We conducted a register-based cohort study encompassing 3,598,159 children born in Sweden between 1987 and 2020. Childhood bereavement was defined as the death of a biological mother, father or sibling. Diagnosis of type 1 diabetes in childhood (<18 years) was ascertained through the National Patient Register. We applied a Cox proportional hazards regression model to investigate the impact of childhood bereavement on type 1 diabetes, while adjusting for potential confounders (including parental type 1 diabetes status, country of birth and demographic characteristics).

RESULTS: During follow-up, 86,226 children (2.4%) lost a family member, and 18,817 children (0.52%) were diagnosed with type 1 diabetes (median age at onset 9.1 years). We did not detect any overall association between childhood bereavement and type 1 diabetes (adjusted HR 1.04; 95% CI 0.93, 1.17). We found no influence of age at loss, cause of death, familial relationship to the deceased, and time since loss.

CONCLUSIONS/INTERPRETATION: In this large population-based Swedish study, we observed no evidence supporting a link between childhood bereavement and type 1 diabetes.

INTRODUCTION: Despite increasing numbers of working-age cancer survivors, evidence on their future work-related circumstances is limited. This study examined their future sick leave, disability pension, and unemployment benefits compared to matched cancer-free individuals.

METHODS: A matched cohort study was conducted using nationwide Swedish registers. In total, 94,411 individuals aged 25 to 59 years when diagnosed with incident cancer in 2001-2012 and who returned to work after cancer were compared with their matched cancer-free individuals (N = 354,814). Follow-up started from the year before cancer diagnosis and continued up to 14 years. Generalized estimating equations were used to calculate incidence rate ratios (IRR) and odds ratios for the difference between cancer survivors and matched cancer-free individuals.

RESULTS: Compared with cancer-free individuals, cancer survivors had six times higher sick-leave days per year after cancer (IRR 6.25 [95% CI, 5.97-6.54] for men; IRR, 5.51 [5.39-5.64] for women). This higher number of sick-leave days declined over time but a two-fold difference persisted. An approximate 1.5 times higher risk of receiving disability pension remained during follow-up. The unemployment days tended to be lower for cancer survivors (IRR, 0.84 [0.75-0.94] for men; IRR, 0.91 [0.86-0.96] for women). Risk of sick leave and disability pension was higher among those with leukemia, colorectal, and breast cancer than skin and genitourinary cancers.

CONCLUSIONS: Cancer survivors who returned to work experienced a high and persisting sick leave and disability pension for over a decade. Prolonged receipt of a high amount of benefits may have long-term adverse impacts on financial circumstances; more knowledge to promote the environment that encourages returning to and remaining in work is needed.