BACKGROUND:SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS:In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS:The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322 597 treatment episodes among 282 282 patients with type 2 diabetes (mean age 63 years, 116 521 [36·1%] of 322 597 women). During a median (IQR) follow-up of 1·3 (0·7-2·8) years, 1452 ketoacidosis events occurred (incidence 2·43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (≥83 vs ≤52 mmol/mol: odds ratio [OR] 15·37 [95% CI 11·50-20·53]), malnutrition (OR 10·54 [7·32-15·18]), previous ketoacidosis (OR 10·40 [7·09-15·24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9·98 [5·68-17·53]), and recent hypoglycaemia (OR 5·22 [2·60-10·49]). Infection was the most common precipitating or co-occurring event (454 [31·8%] of 1428 vs 862 [6·1%] of 14 233 for ketoacidosis cases vs controls; OR 7·60 [6·62-8·71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25·1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31·9%) of 842 to 615 (73·0%) of 842. INTERPRETATION:Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING:Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Abstract Introduction Colon ischemia (CI) is the most common form of intestinal ischemia, yet case identification in epidemiological research remains challenging due to heterogeneous diagnostic criteria and absence of a specific ICD code. The use of SNOMED (Systematized Nomenclature of Medicine) for gastrointestinal biopsies and surgical specimens enables a unique possibility to identify CI cases. Methods In this validation study, 231 individuals with SNOMED code M54 (necrosis) and colorectal topography codes (T67-T68) were randomly selected from five Swedish regions. Medical charts were retrieved for 204 cases, where 143 contained sufficient information for evaluation. Cases were classified according to Brandt & Boley criteria and assigned an etiological group. Positive predictive values (PPVs) were calculated for overall IC based on histopathology alone and for etiological subsets where histopathology was combined with ICD codes. Results Histopathology confirmed ischemia of any cause in 99% (141/143) cases. According to Brandt & Boley criteria, 14 (10%) patients had definite CI, 0 had probable CI, 78 (54%) had possible CI, and 51 (36%) no CI. Common triggers included postoperative complications after treatment for colorectal cancer, intestinal obstruction, inflammatory disorders, arterial disease. Idiopathic CI was the most common etiological group (44%). Combining SNOMED with ICD codes yielded a PPV of 84% for idiopathic CI, increasing to 92% when using stricter ICD-10 criteria (K55.x or K52.8/9). Discussion Histopathology-based identification using SNOMED codes provides high diagnostic accuracy for CI of any cause. Combining SNOMED with ICD codes offers a feasible approach to identify patients with idiopathic CI, for future population-based research.

BACKGROUND:There are concerns about a possible link between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and nonarteritic anterior ischemic optic neuropathy (NAION). OBJECTIVE:To examine whether use of GLP-1RAs increases risk for AION, which predominantly comprises NAION. DESIGN:Nationwide, register-based, cohort study. SETTING:Sweden, 2013 to 2024. PATIENTS:Initiators of GLP-1RAs compared with initiators of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. MEASUREMENTS:Anterior ischemic optic neuropathy in the national patient register. Adjusted risk differences (RDs) and risk ratios (RRs) were estimated using propensity score weighting. RESULTS:Median follow-up was 1.6 years (IQR, 0.7 to 3.1 years) for GLP-1RA users and 1.5 years (IQR, 0.7 to 2.9 years) for SGLT-2 inhibitor users. Sixty-two of 107 518 GLP-1RA users and 64 of 185 898 SGLT-2 inhibitor users experienced AION. Risks were 0.04% versus 0.02% (RD, 0.02% [95% CI, 0.00% to 0.03%]; RR, 1.93 [CI, 1.00 to 3.73]) at 1 year and 0.12% versus 0.07% (RD, 0.05% [CI, 0.00% to 0.10%]; RR, 1.69 [CI, 0.95 to 3.01]) at 5 years. The differences were substantially attenuated in analyses restricted to patients receiving metformin at baseline (1 year: RD, 0.01% [CI, -0.01% to 0.02%]; RR, 1.40 [CI, 0.64 to 3.05]; 3 years: RD, 0.01% [CI, -0.02% to 0.04%]; RR, 1.24 [CI, 0.68 to 2.26]; 5 years: RD, 0.02% [CI, -0.04% to 0.08%]; RR, 1.23 [CI, 0.65 to 2.33]). LIMITATION:Few outcome events, unmeasured confounding, and limited generalizability to GLP-1RA users without diabetes. CONCLUSION:The relative risk for AION was higher with GLP-1RA use compared with SGLT-2 inhibitor use in type 2 diabetes. However, absolute risks were small, and the RDs were substantially reduced in analyses restricted to patients receiving metformin to better account for confounding by diabetes severity, suggesting observed increases in risk may reflect residual confounding. PRIMARY FUNDING SOURCE:Karolinska Institutet, Swedish Society of Medicine, Swedish Research Council, and Region Stockholm.

Importance Phototherapy is widely used in the care of preterm newborns to prevent brain damage resulting from hyperbilirubinemia. However, concerns regarding its safety have been raised. Objective To determine the associations between phototherapy and neonatal mortality or morbidity. Design, Setting, and Participants This population-based cohort study from the Swedish Neonatal Quality Register included preterm newborns (gestational age, 22-31 weeks) admitted for care between November 2015 and December 2024, and followed up to hospital discharge. Deaths before 7 days of age, major congenital anomalies, or newborns without data on phototherapy were excluded. Exposures Duration of phototherapy categorized as 0 to 3, 4 to 5, and 6 to 7 days. Peak bilirubin levels in the first week were categorized as less than 25th, 25th to 50th, 51st to 75th, and greater than 75th percentiles. Main Outcomes and Measures The primary outcome was late neonatal mortality (LNM) on postnatal days 8 to 27 with a composite of severe neonatal morbidity as secondary outcome: intraventricular hemorrhage (IVH) grade 3 to 4; treated patent ductus arteriosus; necrotizing enterocolitis stage IIa or higher; severe bronchopulmonary dysplasia (BPD); or retinopathy of prematurity. Adjusted odds ratios (aORs) were calculated and adjusted for multiple pregnancy, preeclampsia, cesarean delivery, newborn sex, gestational age, Apgar score less than 4 at 5 minutes, and being small for gestational age or large for gestational age. Results This study included a total of 4970 newborns. Median (IQR) gestational age was 29.1 (26.7-30.7) weeks, the median (IQR) birth weight was 1180 (860-1510) g, 2741 newborns (55.2%) were male, and 4746 newborns (95.5%) were treated with phototherapy. LNM occurred in 34 of 1995 newborns (1.7%) treated with phototherapy for 0 to 3 days, in 55 of 1921 newborns (2.9%) treated 4 to 5 days, and in 48 of 1054 newborns (4.6%) treated 6 to 7 days. Compared with 0 to 3 days of phototherapy, the aOR for LNM after 4 to 5 was 1.13 (95% CI, 0.71-1.78), and that for 6 to 7 days of treatment was 1.01 (95% CI, 0.62-1.65). Excluding newborns with IVH, hemolytic disease, or Apgar score below 4 at 5 minutes did not alter the results; neither did an evaluation of phototherapy duration and LNM stratified by peak bilirubin categories. Compared with 0 to 3 days, the aOR for composite morbidity after 4 to 5 days of phototherapy was 1.29 (95% CI, 1.04-1.59), and that for 6 to 7 days of phototherapy was 1.66 (95% CI, 1.31-2.09), which could be attributed to more prevalent IVH and severe BPD in newborns with longer treatment durations. Conclusions and Relevance In this cohort study of very preterm newborns, the duration of phototherapy for hyperbilirubinemia was not associated with neonatal mortality. Nevertheless, prolonged phototherapy in very preterm newborns should be avoided.

BACKGROUND:Findings conflict regarding the risk of peripartum mental illness in women with multiple sclerosis (MS) and how this compares to the risk among women with other chronic diseases. We compared the incidence and prevalence of peripartum mental illness among women with MS, epilepsy, inflammatory bowel disease (IBD), diabetes, and women without any of these diseases (comparators). METHODS:Using population-based Swedish administrative health data we selected women with MS, epilepsy, IBD, diabetes, and comparators who had deliveries between 2002 and 2019. Using validated case definitions for peripartum mental illness we estimated the incidence and prevalence of mental illness during the period encompassing pregnancy and the first post-partum year. We compared incidence and prevalence between cohorts using crude estimates and unadjusted Poisson regression. RESULTS:We included 1096,814 women (1936 MS; 7709 epilepsy; 7731 IBD; 7182 diabetes; 1072,256 comparators). Mean (SD) age at conception was 30.1 (5.1) years. Compared to comparators, mothers with MS had a higher incidence of any mental illness (incidence rate ratio [IRR] 1.36; 1.04-1.78), as did mothers with epilepsy (1.78; 1.58-2.00), IBD (1.46; 1.28-1.66) and diabetes (1.61; 1.41-1.83). Mothers with MS, epilepsy, IBD and diabetes also had a higher incidence and prevalence of depression and bipolar disorder than comparators. Mothers with epilepsy had higher incidence rates of anxiety, and higher prevalence ratios of any mental illness and anxiety than mothers with MS. CONCLUSIONS:Women with MS, epilepsy, IBD and diabetes have a similarly elevated incidence and prevalence of peripartum mental illness as compared to mothers without these conditions.

BACKGROUND AND AIMS:Absolute risk estimates of serious infections in inflammatory bowel disease (IBD) across therapies and concomitant corticosteroid treatment are limited. We aimed to assess serious infection risk in IBD patients receiving different therapies, with or without corticosteroids. METHODS:Using nationwide Swedish registers (2007-2024), we compared rates of serious infections in patients with IBD treated with different therapies versus matched population comparators (≤10 per patient), stratified by corticosteroid use. We also performed 1:1 propensity score (PS)-matching for direct comparison of infection risk in IBD with or without concomitant corticosteroids exposure across advanced therapies. Incidence rates and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated. RESULTS:We identified 145,125 exposure periods in patients with IBD naïve to immunomodulators and advanced therapies, 82,675 to immunomodulators, and 90,181 to advanced therapies (TNF inhibitors with and without immunomodulator, anti-integrins, anti-interleukins, and JAK inhibitors). Across therapies, exposure periods with corticosteroids carried a higher risk of serious infections than periods without, both compared to the general population (incidence rate difference range=3.6-10.2/100 person-years; aHR range=4.52-15.86) and in PS-matched within therapy group comparisons (incidence rate difference range=3.9-8.5/100 person-years; aHR=1.82-3.60). Relative risk was highest in children and increased with cumulative corticosteroid dose. CONCLUSION:Patients with IBD receiving corticosteroids had significantly higher rates of serious infections compared with those not receiving corticosteroids across therapies, with rate differences across age groups and combinations of treatments. These data will inform infection risk assessment and consideration of individualized infection-prevention strategies.

BACKGROUND:We aimed to assess the risk of serious infections in patients with inflammatory bowel disease (IBD) exposed to different advanced therapies. METHODS:We linked nationwide registers and compared rates of incident serious infections in patients with Crohn's disease (CD) and ulcerative colitis (UC) exposed to medical therapies versus matched general population comparators during 2007-2023. We 1:1 propensity score-matched individuals with IBD to compare infection risk across therapies. RESULTS:We identified 55 866 patients with IBD naïve to immunomodulators (IMM) and advanced therapies, 20 392 exposed to IMM, 15 973 to anti-tumor necrosis factor (anti-TNF), 9035 to IMM with anti-TNF, 3948 to vedolizumab, 2926 to ustekinumab, 659 to tofacitinib, 987 to upadacitinib, 262 to filgotinib, and 163 to risankizumab with 987 366 matched comparators with up to 18 years of follow-up. Compared to the general population (incidence rate range 0.39-1.13 per 100 person-years [PY]), patients with IBD had a higher incidence of serious infections (naïve 2.31 per 100 PY; adjusted hazard ratio [aHR] 1.89, 95% confidence interval [CI] 1.84-1.94), IMM 3.27 per 100 PY (aHR 4.45, 95% CI 4.24-4.66), and advanced therapies 3.14-8.10 per 100 PY (aHR 3.45-10.55, 95% CI 3.04-26.65). Relative risks were elevated in the pediatric population, and for opportunistic and gastrointestinal infections. No differences in infection rates were observed in propensity score-matched comparisons of different advanced therapies. CONCLUSION:Patients with IBD were at an increased risk of infections, even among those naïve to IMM and advanced therapies. There was no significant difference in the risk of infections across advanced therapy exposures.

BACKGROUND & AIMS:Antibiotic exposure has, albeit inconsistently, been linked to future celiac disease (CD), but may reflect health care-seeking behavior or treatment of undiagnosed CD. We examined prior antibiotic use in individuals with biopsy-verified CD vs their matched general population comparators and siblings. We also compared associations with individuals with normal mucosa. METHODS:This nationwide Swedish study (2007-2023) assessed antibiotic use up until 1 year before diagnosis/matching in 27,789 individuals with biopsy-verified CD, 133,451 comparators, and 33,112 siblings. Secondary analyses included individuals with histologically normal mucosa (n = 225,548) vs matched comparators (n = 1,089,796). Odds ratios (aORs) were adjusted for comorbidities, socioeconomic status, and health care use. RESULTS:Earlier antibiotic exposure was more common in CD (69%) than in comparators (63%; aOR, 1.24; 95% confidence interval [CI], 1.21-1.28). Restricted analyses to antibiotics ≥5 years before CD diagnosis yielded an aOR of 1.15 (95% CI, 1.11-1.19). The association increased with the number of dispensations (aOR, 1.21; 95% CI, 1.17-1.25 for 1-2; 1.35; 95% CI, 1.30-1.41 for ≥3 vs none). The association between CD and prior antibiotics persisted in sibling comparisons (any use: aOR, 1.29; 95% CI, 1.24-1.35). An even stronger association with antibiotics was seen among individuals with normal mucosa (aOR, 1.50; 95% CI, 1.48-1.51), with a particularly elevated risk in those with ≥3 earlier dispensations (aOR, 1.80; 95% CI, 1.78-1.83). CONCLUSIONS:Individuals with CD were more often exposed to antibiotics before diagnosis than their general population comparators. However, an even stronger association with antibiotic use was seen in those with normal mucosa, suggesting that heightened surveillance rather than causality may contribute to the observed patterns. Although antibiotic stewardship remains important, CD concerns should not deter appropriate antibiotic use.

Context: The effect of autoimmune Addison's disease (AAD) on work ability and income over time remains unclear. Objective: This work aimed to evaluate differences and temporal trends in income and lost workdays among patients with AAD before and after diagnosis, vs matched general population comparators. This nationwide, register-based cohort study was conducted in Sweden. We linked the Swedish Addison Register with national health registers to identify 716 working-age individuals (aged 20-62 years) with incident AAD 2003 to 2019 and 3271 general-population comparators matched by sex, age, county, calendar year, and education level. Annual work loss, taxable earnings, and disposable income were examined over a 10-year period around diagnosis using linear (work loss) and quantile (earnings, income) regression. Results: Patients with AAD had significantly more work loss than comparators from 1 year before to 3 years after diagnosis, with the largest difference the year after diagnosis (mean difference: 30.5 days; 95% CI, 22.9-38.0 days). Median taxable earnings were lower in patients with AAD 1 year before (median difference: $-1107; 95% CI, $-2042 to $-173; P = .02) and 1 year after diagnosis ($-1105; 95% CI, $-2166 to $-43; P = .04). Disposable income was also reduced 1 year after diagnosis (median difference: $-1084; 95% CI, $-1813 to $-354; P = .004). Conclusion: In AAD, increased work loss and reduced earnings and income were concentrated around diagnosis, peaking in the year after. Reassuringly, both absence from work and income normalized within 4 years following diagnosis.

BACKGROUND:We aimed to determine corticosteroid (CS) use in paediatric inflammatory bowel disease (PIBD, < 18 years), which remains common despite recommendations for limited use and the emergence of steroid-sparing therapies. METHODS:We conducted a study of all children in Sweden diagnosed with CD (n = 2460) or UC (n = 2470) in 2006-2022. Nationwide health registers provided annual individual-level data on CS use, classified as any use and excess use (i.e., ≥ 2 courses or ≥ 3 months of use per year). RESULTS:The mean age at diagnosis was 13.7 (SD = 3.4) for CD and 13.9 (SD = 3.8) years for UC. In CD, the proportion of patients with any annual CS use decreased from 42.9% (2006) to 27.6% (2022; p < 0.001), particularly for excess CS use (decreasing from 33.7% to 19.1%; p < 0.001). Rates in UC remained largely unchanged, with any CS use at 41.0% in 2006 and 43.6% in 2022 (p = 0.43), while excess use was 32.4% in 2006 and 36.2% in 2022 (p = 0.21). Although any CS use was most common during the first year after diagnosis (CD: 63.8%, UC: 70.6%), annual rates stabilised only during the fourth (CD) and fifth (UC) years of diagnosis. Older age at diagnosis and prior IBD-related hospitalisation were risk factors for excess CS use in both CD and UC. CONCLUSIONS:The use of CS in PIBD remains high, with annual rates showing no reduction in UC over the past more than 15 years, while a marked decline is observed in CD. Our data should inform strategies to reduce excess CS use in children.

INTRODUCTION:Real-world data quantifying absolute cancer risk in Crohn's disease (CD) by treatment status are lacking but are essential for patient counselling. METHODS:We linked nationwide Swedish register data and assessed incident cancers overall and by type in patients with CD 2007-2023. We estimated age-stratified incidence rate (IR) differences compared with the general population in a once-exposed-always-exposed design. Treatment cohorts comprised new users of thiopurine, tumor necrosis factor inhibitors (TNFi), thiopurine + TNFi, vedolizumab, ustekinumab, and patients naïve to immunomodulatory drugs. RESULTS:We followed 38,733 patients and 360,616 comparator subjects for a median 7.3 years. The IR differences for any cancer (number of excess cancers in each treatment cohort per 1,000 person-years versus the matched population) were 2.43 (95% CI: 1.92; 2.94) for the naive cohort; 3.14 (95% CI: 2.50; 3.78) for thiopurine-treated, 2.42 (95% CI: 1.63; 3.22) for TNFi-treated, 2.59 (95% CI: 1.53; 3.64) for thiopurine + TNFi, 2.61 (95% CI: -0.08; 5.30) for vedolizumab, and 1.54 (95% CI: -1.34; 4.41) for ustekinumab. The excess cancer incidence was primarily because of nonmelanoma skin cancer (squamous cell and basal cell carcinoma). After exclusion of nonmelanoma skin cancers, the excess overall cancer incidence was 1.27 to 0.96 cases/1,000 person-years in the naïve, thiopurine, and TNFi-treated groups, but not significantly increased in the other. IR differences for overall cancer increased and hazard ratios decreased with increasing patient age. DISCUSSION:Elevated overall cancer incidence was observed across all treatment cohorts, also in treatment-naïve patients. After exclusion of nonmelanoma skin cancer, the excess cancer incidence in CD was around 1 extra case per 1,000 person-years because of lung, small bowel, hepatobiliary, and hematologic cancers.

BACKGROUND & AIMS:Celiac disease (CeD) is associated with chronic diseases of the liver, kidney, and heart. Despite this, the risk of severe disease requiring transplantation has not been established. Our objective was to measure the risk of solid organ transplantation in individuals with celiac disease relative to that of the general population. METHODS:This was a population-based matched cohort study in Sweden. We identified individuals with biopsy-proven celiac disease diagnosed between 2000 and 2023 using the nationwide histopathology cohort, ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden). We calculated the incidence of solid organ transplantation (liver, heart, kidney, and lung) in patients with celiac disease and estimated the risk relative to the general population using Cox proportional hazards models. In secondary analyses, we estimated the risk of liver, heart, and kidney transplants specifically. RESULTS:We identified 41,277 individuals with celiac disease and 196,863 age- and sex-matched comparators. During a mean follow-up of 12.1 years, there were 85 solid organ transplantations in patients with celiac disease (17.0 per 100,000 person-years) and 111 in matched comparators (4.6 per 100,000 person-years). This corresponded to an adjusted hazard ratio of 2.76 (95% confidence interval, 1.96-3.89). There was a significantly increased risk of liver transplantation (hazard ratio, 7.26; 95% confidence interval, 3.88-13.56) and kidney transplantation (hazard ratio, 1.85; 95% confidence interval, 1.11-3.10), but the hazard ratio for heart transplantation did not attain statistical significance (hazard ratio, 2.35; 95% confidence interval, 0.84-6.61). CONCLUSIONS:In this nationwide study, celiac disease was associated with an almost 3-fold increased risk of solid organ transplantation, particularly liver transplantation. Further research is needed to explore the pathophysiological relationship between celiac disease and end-stage organ disease.

Ulcerative colitis (UC) is a chronic immune-mediated disease of the large intestine, characterized by recurrent or persistent inflammation. Chronic systemic inflammation may increase the long-term risk of comorbidities such as cardiovascular disease (CVD), diabetes, and dementia, and these risks can be further amplified by corticosteroid use. Early colectomy, however, may mitigate these cardiometabolic risks by definitively eliminating the source of ongoing inflammation and need for continued medical treatment. Therefore, in this nationwide matched cohort study, we compared the long-term risk of cardiometabolic disease among individuals who underwent colectomy within the first two years of UC diagnosis vs. those who did not. Using Swedish nationwide registries, we identified all individuals aged ≥18 years with UC between July 2006 and December 2023. Individuals who had an early colectomy (≤2 years from diagnosis) were matched 1:1 to individuals without an early colectomy, based on age, sex, and calendar year (exact match at UC diagnosis). Additionally, nearest neighbor propensity scores were used to balance demographics and IBD- and clinical characteristics at colectomy. The primary outcome was incident CVD, with diabetes and dementia assessed as secondary outcomes. Cox proportional hazards models were then used to obtain adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). In the primary analysis, 1,832 individuals with UC and no prior history of CVD were included: 916 who underwent early colectomy (median time to colectomy 92 days) and 916 who did not undergo early colectomy. The median age at inclusion was 45.4 years, and 64.6% were male. During a median follow-up time of 8.8years, 8.0% developed CVD in the early colectomy group as compared with 11.4% in the non-colectomy group (aHR 0.68, 95% CI 0.44–1.06; Figure 1, Table 1). The proportion of individuals who developed dementia was numerically reduced by half among those who underwent early colectomy (1.2% vs. 2.4%), although this difference was not statistically significant (aHR 0.07, 95%CI 0.00-36.14). A similar pattern was observed for diabetes, with a numerically lower risk observed in the early colectomy group (aHR 0.76, 95% CI 0.39–1.48; Table 1). In this nationwide matched cohort study of individuals with UC, colectomy within two years of diagnosis was associated with a numerically lower risk of CVD, diabetes and dementia. These findings suggest that early surgical intervention may help mitigate the risk of inflammation-related cardiometabolic disease, although further studies are needed to confirm these associations and evaluate long-term outcomes. Conflict of interest: Dr. Faye, Adam: Consulting/Educational funding from: AbbVie, Takeda, Eli Lilly Kochar, Bharati: Speaking or advisory/consulting fees from Bristol Myers Squibb, Janssen, Merck, Pfizer Inc., and Takeda Axelrad, Jordan: Research grants from BioFire Diagnostics, Genentech, Janssen, and Takeda. Consultancy fees, honorarium, or advisory board fees from Abbvie, Abviax, Adiso, BioFire Diagnostics, Biomerieux, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Pfizer, Sanofi, Takeda, and Vedanta. Sun, Jiangwei: No conflicts Nordenvall, Caroline: none Halfvarson, Jonas: Grant support: Swedish Foundation for Strategic Research (RB13-0160 to J.H.), the Swedish Research Council (2020-02021 to J.H.), the Örebro University Hospital research foundation (OLL-890291 to J.H.), NordForsk (90569 to J.H.) and Vinnova (2019-01185 to JH and 2024-01155 co-applicant), IHI, EU, INTERCEPT (Grant agreement number 101194780, co-applicant), miGut-Health, HORIZON-HLTH-2022, EU (Grant Agreement 101095470, Co-applicant), 3TR, IMI 2, EU, (Grant agreement number 831434, Co-applicant), Janssen, MSD, and Takeda. Consulting and/or advisory board fees from: AbbVie, Alfasigma, Aqilion, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Hospira, Index Pharmaceuticals, Janssen, Johnson & Johnson, MEDA, Medivir, Medtronic, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, Thermo Fisher Scientific, Tillotts Pharma, Vifor Pharma, UCB and speaker’s fees from: AbbVie, Alfasigma, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, Hospira, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma and research grant support from Janssen, Merck Sharp & Dohme and Takeda. Olen, Ola: Karolinska Institutet has received research grants from Pfizer, Janssen, AbbVie, Takeda, Ferring, Bristol Myers Squibb, and Alfasigma for projects led by Olén. Ola Olén has also received fees for lectures from Pfizer, Janssen, Bristol Myers Squibb, and Takeda. Soderling, Jonas: None Ludvigsson, Jonas: Dr Ludvigsson has received financial support from Merck/MSD for a study on inflammatory bowel disease and fibrosis and for developing a paper reviewing national healthcare registers in China. Dr Ludvigsson also has an ongoing research collaboration on celiac disease with Takeda. Earlier support includes a grant from Janssen for an unrelated study on behalf of the Swedish IBD quality register (SWIBREG).

ABSTRACT Background and Aims Studies show that corticosteroid use in inflammatory bowel disease (IBD) exceeds guideline recommendations. To better understand patterns of corticosteroid use and identify factors associated with excess exposure, we examined long‐term trends in corticosteroid prescribing practices in large IBD populations across 3 countries. Methods This retrospective analysis used data from US administrative claims (2007–2018) and national registries from Sweden (2006–2022) and Denmark (1995–2018). The prevalent cohort included patients with ≥ 2 records of an IBD diagnosis since data collection. The incident cohort included patients with a new IBD diagnosis. Excess corticosteroid use was defined as ≥ 2 separate corticosteroid courses within 1 year and/or continuous corticosteroid exposure ≥ 3 months. We conducted multivariable logistic regression to identify variables associated with excess use. Results In prevalent cohorts, including 257,359 (United States), 75,301 (Sweden), and 46,785 (Denmark) patients, annual rates of corticosteroid use and excess declined over the study period in the United States (use: CD [28.1 → 26.4%], UC [31.6 → 27.5%]; excess: CD [13.7 → 11.3%], UC [16.9% → 11.8%]), Sweden (use: CD [29.8% → 20.9%], UC [21.5% → 14.8%]; excess: CD [22.8% → 15.2%], UC [14.8% → 9.5%]), and Denmark (use: CD [15.5% → 10.0%], UC [12.1% → 8.5%]; excess: CD [6.8% → 3.2%], UC [4.9% → 2.5%]). In incident cohorts, including 106,845 (United States), 45,347 (Sweden), and 37,681 (Denmark) patients, corticosteroid use and excess were highest during the first year post‐diagnosis. During years 2‐4 post‐diagnosis, IBD complications, IBD‐related hospitalizations, and previous advanced therapy exposure (excluding CD Danish cohort) were associated with excess use. Conclusions Corticosteroid use decreased over time, though exposure varied across countries. Corticosteroid use and excess were highest during the first year after diagnosis.

BACKGROUND & AIMS:Individuals with inflammatory bowel disease (IBD) have an elevated risk of colorectal neoplasia (CRN), including colorectal dysplasia and cancer (CRC). Despite surveillance strategies to prevent CRC, the clinical course of dysplasia types remains poorly understood. METHODS:We conducted a nationwide cohort study using the Swedish Patient Register and the ESPRESSO histopathology cohort to identify patients diagnosed with IBD between 1969 and 2023. Patients were classified according to their first (baseline) incident episode of dysplasia (no dysplasia [ND]; indefinite [IND]; low-grade [LGD]; high-grade [HGD]). Our primary outcome was future advanced CRN (HGD or CRC) during follow-up. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS:We identified 54,534 patients with IBD, including 1320 with a first (baseline) episode of dysplasia (264 IND, 1031 LGD, 25 HGD), and 53,214 with ND. Over a median follow-up of 13.3 years, 2.3% of patients with ND had future advanced CRN compared with 5.3% of patients with IND (aHR, 1.85; 95% CI, 1.09-3.15) and 8.3% of patients with LGD (aHR, 3.51; 95% CI, 2.77-4.45). Of those with HGD, 40% developed CRC (aHR, 47.88; 95% CI, 25.53-89.80). Risk factors for future dysplasia included male sex, younger age at diagnosis, extensive colitis, primary sclerosing cholangitis, and histologic inflammation. CONCLUSIONS:Patients with IBD and dysplasia have a significantly increased risk of future dysplasia, particularly among patients with HGD. Personalized surveillance strategies based on risk factors are critical for preventing advanced CRN.

BACKGROUND:Obesity is increasing among patients with inflammatory bowel disease, but bariatric surgery has been rare in this group owing to concerns about worsening the inflammatory bowel disease. The aim of the study was to evaluate inflammatory bowel disease-related outcomes following bariatric surgery. METHODS:Nationwide cohort of all adult patients in Sweden between 2007 and 2020 with obesity and inflammatory bowel disease. Patients were matched 1 : 1 with a two-stage matching process between those undergoing bariatric surgery with those who did not (classified by inflammatory bowel disease subtype followed by a propensity score match including sex, age, number of previous targeted therapies, presence of immunotherapy, cumulative oral corticosteroid dose, and previous intestinal surgery). The primary composite outcome comprised inflammatory bowel disease-related hospitalization, initiation of corticosteroid therapy, immunomodulation, commencement of a new targeted therapy or major inflammatory bowel disease-related surgery. RESULTS:The study included 798 patients with inflammatory bowel disease and obesity: 399 who underwent bariatric surgery (145 Crohn's disease, 238 ulcerative colitis, 16 unclassified inflammatory bowel disease) versus 399 who did not. Over a median observation period of 3.3 years in the surgery group and 3.0 years in the non-surgery group, the composite primary endpoint occurred in 201 patients who had surgery (incidence rate 11.9 (95% confidence interval (c.i.) 10.2 to 13.5) per 100 person-years) and 226 without surgery (incidence rate 15.1 (13.1 to 17.0) per 100 person-years), corresponding to an adjusted hazard ratio of 0.66 (95% c.i. 0.51 to 0.85) in those undergoing bariatric surgery compared with those who did not. CONCLUSION:Bariatric surgery was associated with improved inflammatory bowel disease-related outcomes among patients with inflammatory bowel disease and obesity, suggesting a potential benefit from bariatric surgery among patients with concomitant obesity and inflammatory bowel disease.

Pregnant and puerperal women are at increased risk of venous thromboembolism (VTE) owing to hemostatic changes in preparation for childbirth. The objective of this study was to investigate if COVID-19 infection was associated with VTE in pregnancy or 12 weeks postpartum when considering (prophylactic or therapeutic) anticoagulant use. This population-based register study included all women in Sweden and Norway giving birth after 22 gestational weeks, with conception dates from March 2020 to 2022. A PCR-verified COVID-19 test was used as the exposure, and a VTE diagnosis during pregnancy or 12 weeks postpartum was the outcome. Non-infected women consisted of those testing negative and untested individuals. Cox regression analyses, with COVID-19 infection as a time-varying exposure, and adjusted for maternal characteristics and anticoagulant use, provided overall hazard ratios. To evaluate whether there was a particular increased risk of VTE shortly after testing positive for COVID-19, we estimated time-specific risk of VTE in the first 2, 4, 8, 12, and 16 weeks following COVID-19 infection. Data from each country were first analyzed separately and then meta-analyzed. Among 323,868 participants, 46,048 (14.2%) had COVID-19 during pregnancy, and 80 (0.2%) were diagnosed with VTE. Pregnant women with COVID-19 had a higher VTE incidence rate compared to non-infected (4.9 vs. 2.9 per 1000 person-years; adjusted overall hazard ratio [aHR] 1.26, 95% Confidence Interval [CI] 0.80-2.00). The highest risk was within two weeks of infection (aHR 4.63, 95% CI 2.71-7.90) but remained elevated up to 12 weeks post-infection (aHR 1.86, 95% CI 1.17-2.94). In the postpartum period, 8,515 (2.6%) had COVID-19, and 6 (0.07%) were diagnosed with VTE (aHR 5.17, 95% CI 2.50-10.69). Although VTE post-COVID-19 infection was rare, the infection was associated with increased VTE risk during pregnancy and postpartum, even after adjusting for anticoagulant use. These findings should contribute to the individual risk assessment when evaluating the need for prophylactic anticoagulants in pregnancy and postpartum.

BACKGROUND:Statins reduce the risk of inflammatory bowel disease (IBD), however their effect on IBD disease progression is largely unknown. METHODS:We linked Swedish healthcare registers and performed a nationwide cohort study (2006-2020) of 19 788 adults (≥18 years) with ulcerative colitis (UC) and 12 582 with Crohn's disease (CD). Of these, 1733 with UC and 962 with CD were identified as incident statin users after UC or CD diagnosis. After 1:1 propensity score matching, we compared statin users with non-users to estimate the risk of IBD-related surgery, hospitalizations, and disease flares expressed as incidence rates (IRs) and multivariable-adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). For outcomes with statistically significant estimates, we calculated the numbers needed to treat (NNT). RESULTS:During a median follow-up of 3.4 years we observed a reduced risk of IBD-related surgery in statin users (UC, IR: 3.4 [95%CI: 2.1-4.8] per 1000 person-years; CD, IR: 9.2 [6.2-12.2]) compared with non-users in UC (IR: 6.3 [4.2-8.5]; aHR: 0.55 [0.31-0.97]) and CD (IR: 15.4 [11.0-19.7]; aHR: 0.54 [0.33-0.88]). The NNT to avoid one IBD-related surgical event per year of statin treatment were 345 (UC) and 161 (CD). For statin users, the risks of hospitalizations (IR: 17.0 [13.9-20.2]; aHR: 0.68 [0.51-0.91]) and disease flares (IR: 207.4 [193.2-221.6]; aHR: 0.86 [0.77-0.97]) were reduced in UC, but not in CD (IR: 20.3 [15.8-24.9]; aHR: 0.78 [0.56-1.09] and IR: 245.5 [223.9-267.1]; aHR: 1.02 [0.88-1.19]). In UC, NNT for hospitalizations and disease flares were 145 and 15. CONCLUSIONS:Statins were associated with a reduced risk of IBD-related surgery, hospitalizations, and disease flares in patients with UC, and with a reduced risk of IBD-related surgery in patients with CD.

OBJECTIVE:Autoimmune Addison's disease (AAD) is associated with reduced health-related quality of life and possibly reduced employability. The aim of this study was to assess differences in income and work loss between patients with AAD and matched comparators. DESIGN:Nationwide, cross-sectional register-based study. METHODS:By linking the Swedish Addison Register and national health registers, we identified working age (18-64 years) individuals with AAD and general population comparators (matched 1:5 by sex, age, and county of residence). We assessed differences in taxable earnings and disposable income through quantile regression and differences in work loss through linear regression during 2019. RESULTS:We identified 1140 cases with AAD and 5700 comparators (mean age 46.1 years, 48.4% men). Type 1 diabetes was prevalent in 15.7% and 1.1%, respectively. Work loss was higher in AAD; adjusted mean difference 14.4 days; 95% CI, 8.6-20. The adjusted median differences in taxable earnings and disposable income were non-significant overall at -617 (95% CI; -2317 to 1083) and -405 (95% CI; -1417 to 607) €. However, significantly lower taxable earnings and disposable income were found among patients with short education: -5303 (95% CI; -9603 to -992) and -3754 (95% CI; -6486 to -1022) €, or concomitant type 1 diabetes: -5808 (95% CI; -9937 to -1690) and -3349 (95% CI; -6203 to -506) €. CONCLUSION:Patients with AAD had more work loss, yet overall similar taxable earnings and disposable incomes versus comparators. Patients with AAD with shorter education or type 1 diabetes were most socioeconomically vulnerable.