Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.

OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers. METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure. RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma. CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.

Musculoskeletal disorders in Norway: trends in health care utilization and patient pathways: a nationwide register study.

OBJECTIVE: Describe trends in health care utilization, demographic characteristics and patient pathways among patients with musculoskeletal disorders (MSD) in Norway. DESIGN: Register-based cohort study. SETTINGS: Data were obtained from two Norwegian National registries; the Norwegian Control and Payment of Health Reimbursements Database (KUHR) and the Norwegian Patient Registry (NPR). SUBJECTS: Patients with MSD according to ICPC-2 and ICD-10 during 2014-2017. MAIN OUTCOME MEASURES: Patient pathways from the first contact and the following two years, described in a Sankey Diagram for all MSD patients and three common diagnoses: spine pain, osteoarthritis (OA) and fibromyalgia (FM). RESULT: About 26% of the Norwegian population consulted PHC annually while 7% were treated in SHC. Mean age was 47 and 53 years in PHC and SHC, respectively. The proportion of women increased by age. Spine pain was the most common diagnosis; 33% and 22% in PHC and SHC, respectively. Over 90% visited a GP first, 50% of them were treated by PT and/or in SHC during follow-up. Patients visiting the PT first were less likely to be treated in SHC. OA patients were most likely to be treated by more than one health care professional (>70%). CONCLUSION: One third of the Norwegian population consulted health care services due to MSD annually between 2014-2017. GP was the most consulted health care professional. Among MSD patients with long-term use of health care services, 50% were treated by a PT and/or in SHC in addition to a GP.

Potato Consumption and All-Cause and Cardiovascular Disease Mortality - A Long-Term Follow-Up of a Norwegian Cohort.

BACKGROUND: Potatoes are a staple food in many traditional cuisines, yet their impact on long-term risk of cardiovascular disease (CVD) and mortality is unclear, hampering evidence-based dietary guidelines. OBJECTIVES: This study aimed to examine the association between potato consumption and all-cause and CVD-specific death over a substantial follow-up period within a cohort predominantly consuming boiled potatoes. METHODS: Adults from 3 Norwegian counties were invited to 3 health screenings in 1974-1988 (>80% attendance). Dietary data were collected using semiquantitative food frequency questionnaires at each screening to categorize weekly potato consumption (≤6, 7-13, or ≥14 potatoes/wk) and calculate daily cumulative mean intakes (grams/day). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression to estimate HRs and 95% CIs for the association between potato consumption and risk of death from all causes, CVD, ischemic heart disease (IHD), and acute myocardial infarction (AMI). RESULTS: Among 77,297 participants with a mean baseline age of 41.1 y (range: 18.0-63.9 y), we observed 27,848 deaths, including 9072 deaths due to CVD, over a median follow-up of 33.5 y. Participants who consumed ≥14 potatoes/wk had a lower risk of all-cause death compared with those consuming ≤6 potatoes/wk (HR: 0.88; 95% CI: 0.84, 0.93). Potato consumption was associated with a minor, inverse risk of death due to CVD, IHD, and AMI. In continuous analyses of cumulative intakes, each 100 g/d increment was associated with 4% lower risk of death from all causes (HR: 0.96; 95% CI: 0.94, 0.98), CVD (HR: 0.96; 95% CI: 0.93, 0.99), IHD (HR: 0.96; 95% CI: 0.91, 1.00), and AMI (HR: 0.96, 95% CI: 0.91, 1.01). CONCLUSIONS: In this cohort with a generally high consumption of predominantly boiled potatoes, we find modest, inverse associations between potato consumption and death from all causes, CVD, and IHD.

Healthcare experiences of fibromyalgia patients and their associations with satisfaction and pain relief. A patient survey.

OBJECTIVES: The etiology of fibromyalgia (FM) is disputed, and there is no established cure. Quantitative data on how this may affect patients' healthcare experiences are scarce. The present study aims to investigate FM patients' pain-related healthcare experiences and explore factors associated with high satisfaction and pain relief. METHODS: An anonymous, online, and patient-administered survey was developed and distributed to members of the Norwegian Fibromyalgia Association. It addressed their pain-related healthcare experiences from both primary and specialist care. Odds ratios for healthcare satisfaction and pain relief were estimated by binary logistic regression. Directed acyclic graphs guided the multivariable analyses. RESULTS: The patients (n = 1,626, mean age: 51 years) were primarily women (95%) with a 21.8-year mean pain duration and 12.7 years in pain before diagnosis. One-third did not understand why they had pain, and 56.6% did not know how to get better. More than half had not received satisfactory information on their pain cause from a physician, and guidance on how to improve was reported below medium. Patients regretted a lack of medical specialized competence on muscle pain and reported many unmet needs, including regular follow-up and pain assessment. Physician-mediated pain relief was low, and guideline adherence was deficient. Only 14.8% were satisfied with non-physician health providers evaluating and treating their pain, and 21.5% were satisfied (46.9% dissatisfied) with their global pain-related healthcare. Patients' knowledge of their condition, physicians' pain competence and provision of information and guidance, agreement in explanations and advice, and the absence of unmet needs significantly increased the odds of both healthcare satisfaction and pain relief. CONCLUSIONS: Our survey describes deficiencies in FM patients' pain-related healthcare and suggests areas for improvement to increase healthcare satisfaction and pain relief. (REC# 2019/845, 09.05.19).

Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.

INTRODUCTION: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). METHODS: In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use. RESULTS: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. DISCUSSION: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Incidence and Factors Associated With Second Primary Invasive Melanoma in Norway.

Importance: Patients diagnosed with a primary melanoma are at high risk of subsequent melanomas. Understanding the risk of second primary invasive melanoma and associated factors is crucial to optimize patient follow-up. Objective: To assess the incidence rate of second primary invasive melanoma and time between the first and second primary invasive melanoma in the Norwegian population. Design, Setting, and Participants: This population-based cohort study included data from deidentified records of all invasive melanomas diagnosed in Norway in 2008 to 2020, obtained from the Cancer Registry of Norway. Data were from adults aged 18 years or older diagnosed with a first primary melanoma. Data analysis was performed from March to August 2023. Main Outcomes and Measures: The main outcome was the incidence rate of second primary invasive melanoma at least 30 days after the first. Accelerated failure time models were fitted to examine potential associations with patient and tumor characteristics. Median time between first and second primary melanomas and 95% CIs were calculated. The likelihood of, and median interval for, second primary melanomas on the same or different site as the first primary were calculated. Results: A total of 19 196 individuals aged 18 years or older were diagnosed with a first primary melanoma. The mean (SD) age at diagnosis of the first primary melanoma was 62 (16) years (range, 18-104 years), and 9763 (51%) were female. The incidence rate in the year following diagnosis was 16.8 (95% CI, 14.9-18.7) per 1000 person-years, which decreased to 7.3 (95% CI, 6.0-8.6) during the second year and stabilized thereafter. Median time between first and second primaries decreased with advancing age and was 37 months (95% CI, 8-49) in patients younger than 40 years, 18 (95% CI, 13-24) in patients aged 50 to 59 years, and 11 (95% CI, 7-18) in patients aged 80 years or older. The second primary was on the same site as their first primary for 47% (359 patients), and on a different site for 53% (407 patients). The median interval until second melanoma on the same site as the initial melanoma was 12 (95% CI, 7-19) months in men and 22 (95% CI, 11-35) months in women. Conclusions and Relevance: Older age and male sex were associated with an increased risk, suggesting that increased surveillance intensity may be considered for men, especially those older than 50 years, for at least 3 years after their initial diagnosis, regardless of the characteristics of their first invasive melanoma.

Benzene exposure and risk of lung cancer in the Norwegian Offshore Petroleum Worker cohort: a prospective case-cohort study.

OBJECTIVE: The objective of our study was to examine whether occupational exposure to benzene is associated with lung cancer among males in the Norwegian Offshore Petroleum Workers cohort. METHODS: Among 25 347 male offshore workers employed during 1965-1998, we conducted a case-cohort study with 399 lung cancer cases diagnosed between 1999 and 2021, and 2035 non-cases sampled randomly by 5-year birth cohorts. Individual work histories were coupled to study-specific job-exposure matrices for benzene and other known lung carcinogens. Weighted Cox regression was used to estimate HRs and 95% CIs for the associations between benzene exposure and lung cancer, by major histological subtypes, adjusted for age, smoking and occupational exposure to welding fumes, asbestos and crystalline silica. Missing data were imputed. RESULTS: For lung cancer (all subtypes combined), HRs (95% CIs) for the highest quartiles of benzene exposure versus unexposed were 1.15 (0.61 to 2.35) for cumulative exposure, 1.43 (0.76 to 2.69) for duration, and 1.22 (0.68 to 2.18) for average intensity (0.280≤P-trend≤0.741). For 152 adenocarcinoma cases, a positive trend was observed for exposure duration (P-trend=0.044). CONCLUSIONS: In this cohort of offshore petroleum workers generally exposed to low average levels of benzene, we did not find an overall clear support for an association with lung cancer (all subtypes combined), although an association was suggested for duration of benzene exposure and adenocarcinoma. The limited evidence might be due to restricted statistical power.

Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy: maternal and offspring risk factors for cardiovascular disease.

Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy. Methods: The "Cardiovascular Risk Reduction Diet In Pregnancy" (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother-offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants. Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers. Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT05030922).

Occupational exposures of firefighting and urinary tract cancer risk among men in the Norwegian Fire Departments Cohort.

OBJECTIVES: Increased risks of bladder cancer and mesothelioma were the strongest evidence for the recent reclassification of firefighting as carcinogenic (Group 1) by the International Agency for Research on Cancer. Our study aim was to develop indicators for specific firefighting exposures and examine associations with urinary tract cancer (UTC), including bladder cancer. METHODS: We developed indicators for exposure from employment at a fire department or in firefighting jobs, to fire and smoke, and to diesel exhaust for men in the Norwegian Fire Departments Cohort (n=4250). Incident UTC cases were obtained from the Cancer Registry of Norway (1960-2021). Poisson regression was used to estimate incidence rate ratios (IRR) with cumulative exposures grouped into tertiles (reference: lowest exposed tertile) with 0-year, 10-year and 15-year lagging of exposures. RESULTS: During 125 090 person-years of follow-up, there were 76 cases of UTC. IRRs were mostly non-significantly increased in the middle tertile and at or below 1 in the highest tertile for total duration of employment, number of fires attended and fire exposure score with and without lags. In the middle tertile for diesel exhaust exposure, UTC risk was elevated over twofold with 10-year (IRR 2.27, 95% CI 1.22 to 4.20) and 15- year (2.21, 1.18 to 4.16) lags, and near 1 in the highest tertile. Findings for bladder cancer were similar to those for UTC. CONCLUSIONS: Dose-response associations between the exposure indicators and UTC were not observed. Future studies using the indicators with more cases are needed.

A lean additive frailty model: With an application to clustering of melanoma in Norwegian families.

Additive frailty models are used to model correlated survival data. However, the complexity of the models increases with cluster size to the extent that practical usage becomes increasingly challenging. We present a modification of the additive genetic gamma frailty (AGGF) model, the lean AGGF (L-AGGF) model, which alleviates some of these challenges by using a leaner additive decomposition of the frailty. The performances of the models were compared and evaluated in a simulation study. The L-AGGF model was used to analyze population-wide data on clustering of melanoma in 2 391 125 two-generational Norwegian families, 1960-2015. Using this model, we could analyze the complete data set, while the original model limited the analysis to a restricted data set (with cluster sizes ≤ 7 $$ \le 7 $$ ). We found a substantial clustering of melanoma in Norwegian families and large heterogeneity in melanoma risk across the population, where 52% of the frailty was attributed to the 10% of the population at highest unobserved risk. Due to the improved scalability, the L-AGGF model enables a wider range of analyses of population-wide data compared to the AGGF model. Moreover, the methods outlined here make it possible to perform these analyses in a computationally efficient manner.

Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression.

Importance: Cutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients. Objective: To study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment. Design, Setting, and Participants: This population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022. Exposures: Receipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment. Main Outcomes and Measures: Absolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis. Results: The study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis. Conclusions and Relevance: In this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

Exposure to benzene and other hydrocarbons and risk of bladder cancer among male offshore petroleum workers.

BACKGROUND: Occupational exposures constitute the second leading cause of urinary bladder cancer after tobacco smoking. Increased risks have been found in the petroleum industry, but high-quality exposure data are needed to explain these observations. METHODS: Using a prospective case-cohort design, we analysed 189 bladder cancer cases (1999-2017) and 2065 randomly drawn non-cases from the Norwegian Offshore Petroleum Workers cohort. Cases were identified in the Cancer Registry of Norway, while work histories (1965-1998) and lifestyle factors were recorded by questionnaire at baseline (1998). Occupational petroleum-related hydrocarbon exposures were assessed by expert-developed job-exposure matrices. Hazard ratios were estimated by weighted Cox-regressions, adjusted for age, tobacco smoking, education, and year of first employment, and with lagged exposures. RESULTS: Increased risks were found in benzene-exposed workers, either long-term exposure (≥18.8 years, HR = 1.89, 95% CI: 1.14-3.13; p-trend = 0.044) or high-level cumulative benzene exposure (HR = 1.60, 95% CI: 0.97-2.63; p-trend = 0.065), compared with the unexposed. Associations persisted with 20-year exposure lag. No associations were found with skin or inhalation exposure to crude oil, mineral oil (lubrication, hydraulics, turbines, drilling), or diesel exhaust. CONCLUSIONS: The results suggest that exposures in the benzene fraction of the petroleum stream may be associated with increased bladder cancer risk.

Nevus Count, Pigmentary Characteristics, and Melanoma-specific Mortality among Norwegian Women with Melanoma >1.0 mm Thick.

Little is known about if and how nevi and pigmentation are associated with melanoma-specific mortality. However, increased melanoma awareness in people with lighter pigmentation and many nevi may result in earlier diagnosis of thinner less-lethal tumors. The aim of this study was to investigate associations between nevus count (asymmetrical > 5 mm and small symmetrical), pigmentary characteristics (hair colour, eye colour, skin colour, freckling, pigmentary score), and melanoma-specific mortality in subjects with melanomas > 1 mm. Data from the Norwegian Women and Cancer cohort, established in 1991, with complete follow-up of melanoma patients until 2018 through the Cancer Registry of Norway, were used to estimate hazard ratios with 95% confidence intervals for the associations between nevus count, pigmentary characteristics, and melanoma-specific mortality, stratified by tumor thickness using Cox regression. Estimated hazard ratios consistently indicated a higher risk of melanoma death for those with darker vs lighter pigmentary characteristics in patients with tumors > 1.0-2.0 mm and > 2.0 mm thick (e.g. pigmentary score hazard ratio 1.25, 95% confidence interval (0.74-2.13)). Among women with melanomas > 1.0 mm thick, lighter pigmentation and asymmetrical nevi may be associated with lower melanoma-specific mortality, suggesting that factors that increase the risk of melanoma may also be associated with decreased risk of death from melanoma.

Nutritional assessment of women with celiac disease compared to the general population.

BACKGROUND & AIMS: The nutritional quality of a gluten-free diet is debated because of the elimination of grains that are important sources of nutrients. The aim of this cross-sectional study was to perform a nutritional assessment in treated women with celiac disease and ongoing symptoms, and compare dietary intake with a healthy reference group (Norkost 3). METHODS: Celiac disease patients with biopsy confirmed mucosal healing, but persistent gastrointestinal symptoms, were included from an ongoing clinical trial. Nutritional assessment included anthropometrics, blood samples and dietary intake obtained by two 24 h recalls. Dietary intake in celiac women was compared with dietary intake in healthy women (Norkost 3). Two sample t-test was used for comparison of CeD and Norkost 3 women. Adjustment for age, BMI, education and smoking, by use of multiple linear regression analysis, did not change the results. RESULTS: In total, 59 women with celiac disease and 925 women that participated in Norkost 3 were included, with a mean age of 45 years in both groups. Women with celiac disease had a higher proportion of energy (E%) from fat (39 vs 34%, P < 0.001) and saturated fat (15 vs 13%, P = 0.01), a lower E% from protein (16 vs 18%, P = 0.01) and a lower intake of dietary fiber (19 vs 22 g, P = 0.002) compared to Norkost 3 women. Women with celiac disease had a lower intake of bread, fruit and milk, and a higher intake of cereals and cheese compared to Norkost 3 women. The average requirement was not met for several micronutrients, but blood analysis revealed few nutritional deficiencies: two women with insufficient vitamin D status and one with insufficient folic acid status. CONCLUSION: The women with celiac disease had an unbalanced diet with a higher intake of total- and saturated fatty acids and a lower intake of fiber compared to the general population. These findings emphasizes the need for nutritional follow-up of celiac patients and development of nutrient dense gluten-free products.

Extracorporeal Photopheresis as Graft-versus-Host Disease Prophylaxis: A Randomized Controlled Trial.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P = .32). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GVHD between the intervention group (per-protocol; n = 39 of 76) and the control group (n = 77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P = .006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P = .42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.

Association between use of low-dose aspirin and detection of colorectal polyps and cancer in a screening setting.

BACKGROUND: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated. METHODS: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions. CONCLUSION: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.

Use of antihypertensive drugs and risk of cutaneous melanoma: a nationwide nested case-control study.

BACKGROUND: Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk. METHODS: A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004-15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage. RESULTS: Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01-1.15), calcium-channel blockers (RR 1.10, CI 1.04-1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04-1.16), but not for beta blockers (RR 0.97, CI 0.92-1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR. CONCLUSIONS: Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk.

Night shift work and risk of aggressive prostate cancer in the Norwegian Offshore Petroleum Workers (NOPW) cohort.

BACKGROUND: Night shift work may acutely disrupt the circadian rhythm, with possible carcinogenic effects. Prostate cancer has few established risk factors though night shift work, a probable human carcinogen, may increase the risk. We aimed to study the association between night shift work and chlorinated degreasing agents (CDAs) as possible endocrine disrupters in relation to aggressive prostate cancer as verified malignancies. METHODS: We conducted a case-cohort study on 299 aggressive prostate cancer cases and 2056 randomly drawn non-cases in the Norwegian Offshore Petroleum Workers cohort (1965-98) with linkage to the Cancer Registry of Norway (1953-2019). Work history was recorded as years with day, night, and rollover (rotating) shift work, and CDA exposure was assessed with expert-made job-exposure matrices. Weighted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for aggressive prostate cancer, adjusted for education and year of first employment, stratified by 10-year birth cohorts, and with 10, 15, and 20 years of exposure lag periods. RESULTS: Compared with day work only, an increased hazard of aggressive prostate cancer (HR = 1.86, 95% CI 1.18-2.91; P-trend = 0.046) was found in workers exposed to ≥19.5 years of rollover shift work. This persisted with longer lag periods (HR = 1.90, 95% CI 0.92-3.95; P-trend = 0.007). The exposure-hazard curve for a non-linear model increased linearly (HRs ≥1.00) for 18-26 years of rollover shift work. No association was found with CDA exposure. CONCLUSIONS: Long-term exposure to rollover shift work may increase the hazard of aggressive prostate cancer in offshore petroleum workers.