Risk of malignant lymphomas in patients with inflammatory bowel disease: a population-based cohort study.

OBJECTIVE: To estimate the risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) in patients with inflammatory bowel disease (IBD). DESIGN: We undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference. RESULTS: Among 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn's disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9). CONCLUSION: Patients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.

A Comparison of Risk Classification Systems of Colorectal Adenomas: A Case-Cohort Study.

BACKGROUND & AIMS: Because post-polypectomy surveillance uses a growing proportion of colonoscopy capacity, more targeted surveillance is warranted. We therefore compared surveillance burden and cancer detection using 3 different adenoma classification systems. METHODS: In a case-cohort study among individuals who had adenomas removed between 1993 and 2007, we included 675 individuals with colorectal cancer (cases) diagnosed a median of 5.6 years after adenoma removal and 906 randomly selected individuals (subcohort). We compared colorectal cancer incidence among high- and low-risk individuals defined according to the traditional (high-risk: diameter ≥10 mm, high-grade dysplasia, villous growth pattern, or 3 or more adenomas), European Society of Gastrointestinal Endoscopy (ESGE) 2020 (high-risk: diameter ≥10 mm, high-grade dysplasia, or 5 or more adenomas), and novel (high-risk: diameter ≥20 mm or high-grade dysplasia) classification systems. For the different classification systems, we calculated the number of individuals recommended frequent surveillance colonoscopy and estimated number of delayed cancer diagnoses. RESULTS: Four hundred and thirty individuals with adenomas (52.7%) were high risk based on the traditional classification, 369 (45.2%) were high risk based on the ESGE 2020 classification, and 220 (27.0%) were high risk based on the novel classification. Using the traditional, ESGE 2020, and novel classifications, the colorectal cancer incidences per 100,000 person-years were 479, 552, and 690 among high-risk individuals, and 123, 124, and 179 among low-risk individuals, respectively. Compared with the traditional classification, the number of individuals who needed frequent surveillance was reduced by 13.9% and 44.2%, respectively, and 1 (3.4%) and 7 (24.1%) cancer diagnoses were delayed using the ESGE 2020 and novel classifications. CONCLUSIONS: Using the ESGE 2020 and novel risk classifications will substantially reduce resources needed for colonoscopy surveillance after adenoma removal.

Risk of hepato-pancreato-biliary cancer is increased by primary sclerosing cholangitis in patients with inflammatory bowel disease: A population-based cohort study.

BACKGROUND: There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC). OBJECTIVE: To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra - and extrahepatic cholangiocarcinoma. METHODS: In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics. RESULTS: Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8-5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0-2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2-1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123-159) for biliary tract, 38.6 (95% CI 29.2-50.0) for hepatocellular, and 9.0 (95% CI 6.3-12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients. CONCLUSIONS: The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.

Mortality in Norway and Sweden during the COVID-19 pandemic.

Background: Norway and Sweden are similar countries in terms of socioeconomics and health care. Norway implemented extensive COVID-19 measures, such as school closures and lockdowns, whereas Sweden did not. Aims: To compare mortality in Norway and Sweden, two similar countries with very different mitigation measures against COVID-19. Methods: Using real-world data from national registries, we compared all-cause and COVID-19-related mortality rates with 95% confidence intervals (CI) per 100,000 person-weeks and mortality rate ratios (MRR) comparing the five preceding years (2015-2019) with the pandemic year (2020) in Norway and Sweden. Results: In Norway, all-cause mortality was stable from 2015 to 2019 (mortality rate 14.6-15.1 per 100,000 person-weeks; mean mortality rate 14.9) and was lower in 2020 than from 2015 to 2019 (mortality rate 14.4; MRR 0.97; 95% CI 0.96-0.98). In Sweden, all-cause mortality was stable from 2015 to 2018 (mortality rate 17.0-17.8; mean mortality rate 17.1) and similar to that in 2020 (mortality rate 17.6), but lower in 2019 (mortality rate 16.2). Compared with the years 2015-2019, all-cause mortality in the pandemic year was 3% higher due to the lower rate in 2019 (MRR 1.03; 95% CI 1.02-1.04). Excess mortality was confined to people aged ⩾70 years in Sweden compared with previous years. The COVID-19-associated mortality rates per 100,000 person-weeks during the first wave of the pandemic were 0.3 in Norway and 2.9 in Sweden. Conclusions: All-cause mortality in 2020 decreased in Norway and increased in Sweden compared with previous years. The observed excess deaths in Sweden during the pandemic may, in part, be explained by mortality displacement due to the low all-cause mortality in the previous year.

Long-term colorectal cancer incidence and mortality after adenoma removal in women and men.

BACKGROUND: Women and men with colorectal adenomas are at increased risk of colorectal cancer and colonoscopic surveillance is recommended. However, the long-term cancer risk remains unknown. AIMS: To investigate colorectal cancer incidence and mortality after adenoma removal in women and men METHODS: We identified all individuals who had adenomas removed in Norway from 1993 to 2007, with follow-up through 2018. We calculated standardized incidence ratios (SIR) and incidence-based mortality ratios (SMR) with 95% confidence intervals (CI) for colorectal cancer in women and men using the female and male population for comparison. We defined high-risk adenomas as ≥2 adenomas, villous component, or high-grade dysplasia. RESULTS: The cohort comprised 40 293 individuals. During median follow-up of 13.0 years, 1079 women (5.5%) and 866 men (4.2%) developed colorectal cancer; 328 women (1.7%) and 275 men (1.3%) died of colorectal cancer. Colorectal cancer incidence was more increased in women (SIR 1.64, 95% CI 1.54-1.74) than in men (SIR 1.12, 95% CI 1.05-1.19). Colorectal cancer mortality was increased in women (SMR 1.13, 95% CI 1.02-1.26) and reduced in men (SMR 0.79, 95% CI 0.71-0.89). Women with high-risk adenomas had an increased risk of colorectal cancer death (SMR 1.37, 95% CI 1.19-1.57); women with low-risk adenomas (SMR 0.90, 95% CI 0.76-1.07) and men with high-risk adenomas had a similar risk (SMR 0.89, 95% CI 0.76-1.04), while men with low-risk adenomas had reduced risk (SMR 0.70, 95% CI 0.59-0.84). CONCLUSIONS: After adenoma removal, women had an increased risk of colorectal cancer death, while men had reduced risk, compared to the general female and male populations. Sex-specific surveillance recommendations after adenoma removal should be considered.

Covid-19 transmission in fitness centers in Norway - a randomized trial.

BACKGROUND: Closed fitness centers during the Covid-19 pandemic may negatively impact health and wellbeing. We assessed whether training at fitness centers increases the risk of SARS-CoV-2 virus infection. METHODS: In a two-group parallel randomized controlled trial, fitness center members aged 18 to 64 without Covid-19-relevant comorbidities, were randomized to access to training at a fitness center or no-access. Fitness centers applied physical distancing (1 m for floor exercise, 2 m for high-intensity classes) and enhanced hand and surface hygiene. Primary outcomes were SARS-CoV-2 RNA status by polymerase chain reaction (PCR) after 14 days, hospital admission after 21 days. The secondary endpoint was SARS-CoV-2 antibody status after 1 month. RESULTS: 3764 individuals were randomized; 1896 to the training arm and 1868 to the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained ≥six times. Of 3016 individuals who returned the SARS-CoV-2 RNA tests (80.5%), there was one positive test in the training arm, and none in the no-training arm (risk difference 0.053%; 95% CI - 0.050 to 0.156%; p = 0.32). Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (risk difference - 0.87%; 95%CI - 1.52% to - 0.23%; p = 0.001). No outpatient visits or hospital admissions due to Covid-19 occurred in either arm. CONCLUSION: Provided good hygiene and physical distancing measures and low population prevalence of SARS-CoV-2 infection, there was no increased infection risk of SARS-CoV-2 in fitness centers in Oslo, Norway for individuals without Covid-19-relevant comorbidities. TRIAL REGISTRATION: The trial was prospectively registered in ClinicalTrials.gov on May 13, 2020. Due to administrative issues it was first posted on the register website on May 29, 2020: NCT04406909 .

The COVID-19 pandemic in Norway and Sweden - threats, trust, and impact on daily life: a comparative survey.

BACKGROUND: Norway and Sweden have similar populations and health care systems, but different reactions to the COVID-19 pandemic. Norway closed educational institutions, and banned sports and cultural activities; Sweden kept most institutions and training facilities open. We aimed to compare peoples' attitudes towards authorities and control measures, and perceived impact of the pandemic and implemented control measures on life in Norway and Sweden. METHODS: Anonymous web-based surveys for individuals age 15 or older distributed through Facebook using the snowball method, in Norway and Sweden from mid-March to mid-April, 2020. The survey contained questions about perceived threat of the pandemic, views on infection control measures, and impact on daily life. We performed descriptive analyses of the responses and compared the two countries. RESULTS: 3508 individuals participated in the survey (Norway 3000; Sweden 508). 79% were women, the majority were 30-49 years (Norway 60%; Sweden 47%), and about 45% of the participants in both countries had more than 4 years of higher education. Participants had high trust in the health services, but differed in the degree of trust in their government (High trust in Norway 17%; Sweden 37%). More Norwegians than Swedes agreed that school closure was a good measure (Norway 66%; Sweden 18%), that countries with open schools were irresponsible (Norway 65%; Sweden 23%), and that the threat from repercussions of the mitigation measures were large or very large (Norway 71%; Sweden 56%). Both countries had a high compliance with infection preventive measures (> 98%). Many lived a more sedentary life (Norway 69%; Sweden 50%) and ate more (Norway 44%; Sweden 33%) during the pandemic. CONCLUSION: Sweden had more trust in the authorities, while Norwegians reported a more negative lifestyle during the pandemic. The level of trust in the health care system and self-reported compliance with preventive measures was high in both countries despite the differences in infection control measures.

Laparoscopy-assisted versus balloon enteroscopy-assisted ERCP after Roux-en-Y gastric bypass.

BACKGROUND: Patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreatography (ERCP). The most widely used approaches to perform ERCP after RYGB are laparoscopy-assisted ERCP (LA-ERCP) and balloon enteroscopy-assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. We aimed to compare the performance, benefits, and harms of LA-ERCP and BEA-ERCP in RYGB patients. METHODS: We identified all RYGB patients who underwent ERCP at two tertiary care endoscopy centers in Oslo, Norway between May 2013 and December 2017. One center performed BEA-ERCP, the other LA-ERCP. Procedure success was defined as fulfillment of the therapeutic or diagnostic aim, according to the procedure description. Adverse events were classified according to the Clavien-Dindo grading system. RESULTS: During the study period, 40 BEA-ERCP and 39 LA-ERCP procedures were performed in 68 patients. Procedure success rate was 72.5 % for BEA-ERCP and 87.2 % for LA-ERCP (P = 0.14). Adverse events occurred in 18 % of BEA-ERCP and 28 % of LA-ERCP (P = 0.23). Serious adverse events (Clavien-Dindo grade ≥ 3b) occurred in 2.5 % of BEA-ERCP and 7.7 % of LA-ERCP procedures (P = 0.36). Concomitant cholecystectomy was performed in 25 of the 39 LA-ERCP procedures. The median procedure times for LA-ERCP performed with and without concomitant cholecystectomy were 201 minutes and 140 minutes, respectively, and for BEA-ERCP was 125 minutes. CONCLUSIONS: In experienced hands, both LA-ERCP and BEA-ERCP have high success rates after RYGB. The choice of approach should be individualized according to patient characteristics and available physician competence.

Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH. STUDY DESIGN AND METHODS: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records. RESULTS: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 109 /L. CONCLUSIONS: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.

Unraveling the role of maternal anti-HLA class I antibodies in fetal and neonatal thrombocytopenia-Antibody specificity analysis using epitope data.

Anti-HLA class I antibodies have been suggested as a possible cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to characterize maternal anti-HLA class I alloantibodies in suspected cases of FNAIT. The study population consisted of all nationwide referrals of neonates with suspected FNAIT to the National Unit for Platelet Immunology in Tromsø, Norway, during 1998-2009 (cases), and 250 unselected pregnancies originally included in a prospective study (controls). Inclusion criterion was a positive screening for maternal anti-HLA class I antibodies. Neonates with other identifiable causes of thrombocytopenia, including maternal anti-human platelet antigens (HPA) antibodies, were excluded. Ultimately, 50 cases with suspected FNAIT were compared with 60 controls. The median neonatal platelet count nadir among cases was 24×109/L (range 4-98×109/L). Five children (10%) were reported to have intracranial hemorrhage. Maternal and neonatal HLA class I genotype was available for 33 mother/child pairs (66%). Immunization was not tied to any particular HLA class I antigen. Using epitope mapping, we could demonstrate that the maternal anti-HLA class I antibodies were specific towards mismatched paternally-inherited fetal epitopes, with little reactivity towards any third-party epitopes. Antibody reactivity patterns were similar to those found among controls, although the mean fluorescence intensities (MFI) among cases were significantly higher. This study demonstrates the value of using data on HLA epitope expression, instead of HLA antigens, to examine alloimmune responses in connection with neonatal thrombocytopenia. Our findings support the idea that maternal anti-HLA class I antibodies are involved in FNAIT.

Sensitive detection of platelet-specific antibodies with a modified MAIPA using biotinylated antibodies and streptavidin-coated beads.

We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA) with enhanced sensitivity in detecting antibodies against human platelet antigens (HPA), using biotinylated monoclonal antibodies, streptavidin-coated beads and detection by flow cytometry. The beads-MAIPA gave superior signal-to-noise resolution (>10-fold higher) for detection of anti-HPA-1a and anti-HPA-5b compared with the in-house standard MAIPA. Also, efficient and reproducible detection of anti-HPA-15 (CD109) was shown. The enhanced sensitivity was confirmed using WHO International Reference Reagents for anti-HPA-1a, anti-HPA-3a and anti-HPA-5b, which allowed comparison of detection endpoints with other laboratories. Finally, the beads-MAIPA was validated for quantification of anti-HPA-1a. The lower limit of quantification was 0.4IU/mL for beads-MAIPA, compared to 1IU/mL previously reported for standard MAIPA. Based on improved performance against all HPA-antibodies tested, the beads-MAIPA has replaced the standard MAIPA in our laboratory in diagnostics of conditions due to HPA-immunization, such as fetal and neonatal alloimmune thrombocytopenia (FNAIT).