Nationwide Register-based Cohort Study Research Articles

Prevention is still the key to success.

In this issue of the journal, we publish a survey of cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA) in 14 503 patients from 19 countries during 2014–2019. Dr Semb and co-workers report considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for lipid lowering treatment was observed, and only half of the patients obtained blood pressure goal. The authors conclude that despite a high focus on the increased CVD risk in RA patients over the last decade,1 there is still substantial potential for improvement in CVD preventive measures. In recent years, numerous cardiovascular (CV) outcomes trials have demonstrated not only CV safety but reductions in CV outcomes with two new classes of glucose lowering drugs, namely glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in patients with type II DM.2–6 In a Danish study, Dr Nørgaard and co-workers examined CV outcomes associated with the initiation of GLP-1RA vs. SGLT-2i treatment in a real-world setting among patients with type 2 diabetes. They used a Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first-ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015, with follow-up until the end of 2018. The authors concluded that in this nationwide study of patients with type 2 diabetes, initiating GLP-1RA vs. SGLT-2i was not found to be associated with significant differences in CV risk.

Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study.

Animal studies have related glucagon-like peptide 1 receptor agonists (GLP-1) to lower alcohol intake. We examined whether GLP-1 was associated with risk of alcohol-related events in a nationwide cohort study and a self-controlled case series analysis including all new users of GLP1 (n = 38 454) and dipeptidyl peptidase 4 inhibitors (DPP4) (n = 49 222) in Denmark 2009-2017. They were followed for hospital contacts with alcohol use disorder or purchase of drugs for treatment of alcohol dependence in nationwide registers from 2009 to 2018. Associations were examined using Cox proportional hazard and conditional Poisson regression. During follow-up of median 4.1years, 649 (0.7%) of participants were registered with an alcohol-related event. Initiation of GLP-1 treatment was associated with lower risk of an alcohol-related event (Hazard ratio = 0.46 (95%CI: 0.24-0.86) compared with initiation of DPP4 during the first 3months of follow-up. Self-controlled analysis showed the highest risk of alcohol-related events in the 3-month pretreatment period (incidence rate ratio [IRR] = 1.25 (1.00-1.58)), whereas the risk was lowest in the first 3-month treatment period (IRR = 0.74 (0.56-0.97). In conclusion, compared with DPP4 users, individuals who start treatment with GLP-1 had lower incidence of alcohol-related events both in cohort and self-controlled analyses. Thus, there might be a transient preventive effect of GLP1 on alcohol-related events the first months after treatment initiation.

Assessing how routes to diagnosis vary by the age of patients with cancer: a nationwide register-based cohort study in Denmark

BackgroundOlder patients with cancer have poorer prognosis compared to younger patients. Moreover, prognosis is related to how cancer is identified, and where in the healthcare system patients present, i.e. routes to diagnosis (RtD). We investigated whether RtD varied by patients’ age.MethodsThis population-based national cohort study used Danish registry data. Patients were categorized into age groups and eight mutually exclusive RtD. We employed multinomial logistic regressions adjusted for sex, region, diagnosis year, cohabitation, education, income, immigration status and comorbidities. Screened and non-screened patients were analysed separately.ResultsThe study included 137,876 patients. Both younger and older patients with cancer were less likely to get diagnosed after a cancer patient pathways referral from primary care physician compared to middle-aged patients. Older patients were more likely to get diagnosed via unplanned admission, death certificate only, and outpatient admission compared to younger patients. The patterns were similar across comorbidity levels.ConclusionsRtD varied by age groups, and middle-aged patients were the most likely to get diagnosed after cancer patient pathways with referral from primary care. Emphasis should be put on raising clinicians’ awareness of cancer being the underlying cause of symptoms in both younger patients and in older patients.

Extrahepatic autoimmune diseases in autoimmune hepatitis: Effect on mortality.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with an increased prevalence of extrahepatic autoimmune diseases and an increased mortality compared with the general population. The contribution of extrahepatic autoimmune diseases to the increased mortality has not been clarified. Our aim was to determine the effect of extrahepatic autoimmune diseases on mortality in AIH patients. This nationwide register-based cohort study included all Danish patients diagnosed with AIH between 1995 and 2019. We examined the presence of extrahepatic autoimmune diseases and compared the mortality between AIH patients with and without extrahepatic autoimmune diseases. We adjusted our analysis for age, sex, calendar year of AIH diagnosis, cirrhosis, cancer, chronic obstructive pulmonary disease and ischaemic heart disease. We included 2479 AIH patients of whom 19.8% had one extrahepatic autoimmune disease and 3.3% had multiple. The adjusted 10-year cumulative mortality was 27.2% (95% confidence interval [CI]: 25.2-29.4) for patients with extrahepatic autoimmune diseases and 21.6% (95% CI: 19.9-23.6) for patients without. The adjusted mortality hazard ratio was 1.30 (95% CI: 1.12-1.52) for AIH patients with versus without extrahepatic autoimmune diseases; it was 1.25 (95% CI: 1.06-1.48) for patients with one extrahepatic autoimmune disease and 1.54 (95% CI: 1.15-2.05) for those with more than one. Extrahepatic autoimmune diseases increased the mortality in patients with AIH. Patients with multiple extrahepatic autoimmune diseases had a higher mortality than patients with just one extrahepatic autoimmune disease.

Disparities in Reperfusion Therapy and Time Delays Among Patients With Ischemic Stroke and a History of Mental Illness.

Comorbid mental illness may delay recognition of stroke symptoms and reduce the chance of reperfusion therapy. The aim of this study was to compare the use of reperfusion therapy and treatment delays in patients with or without a history of mental illness. A nationwide registry-based cohort study of patients with ischemic stroke. We combined data from the Danish Stroke Registry and the Danish Quality Database for Prehospital Emergency Medical Services from 2016 to 2017 containing information on reperfusion therapy (thrombolysis or thrombectomy) and relevant time stamps. Patients were categorized according to the severity of their mental health history (how recent and severity, for example, hospital- versus primary-based care). A total of 19 592 admissions were included (18% had a minor, 3% had a moderate, and 3% had a history of major mental illness). Significant differences were found regarding age, comorbidity, and socioeconomic factors. Reperfusion therapy was used in 17% of patients. Patients with a history of mental illness were less likely to receive reperfusion therapy: risk ratios with 95% CI were 0.79 (0.72-0.86) for minor, 0.85 (0.72-0.99) for moderate, and 0.63 (0.51-0.77) for patients with a history major mental illness, respectively. Total prehospital delay was longer for patients with a history of major mental illness compared to patients with no history of mental illness, especially when no call had been made to the emergency medical service. The median times from symptom onset to hospital arrival was 811 minutes (197-2845) and 115 minutes (41-188), respectively. We found no differences regarding door-to-needle time, response time, on-scene time, transport time, nor in time-to-imaging among patients arriving within 4 hours from symptoms onset between patients with and without a history of mental illness. Almost one-quarter of patients with ischemic stroke had a history of mental illness. Regardless of severity of mental illness, these patients were less likely to receive reperfusion therapy. Longer delays from symptom onset to hospital arrival contributed to the patients' risk of not being eligible for reperfusion therapy.

Can National Registries Contribute to Predict the Risk of Cancer? The Cancer Risk Assessment Model (CRAM).

Simple SummaryEarly identification of individuals with an increased risk of cancer is an important challenge. Danish administrative registers may be useful in this respect because they cover the entire population and include comprehensive and consistently coded long-term data. We aimed to develop a predictive model based on Danish administrative registers to facilitate the automated identification of individuals at risk of any type of cancer. In addition to age, almost all the included factors contributed statistically significantly, but also only marginally, to the prediction models, which means that we have not overlooked obvious information available in the register. Future prediction studies should focus on specific cancer types where more precise risk estimations might be expected. It is our ultimate ambition that an effective model can be used at the point of care, integrated into electronic patient record systems to alert physicians of patients at a high risk of cancer.Purpose: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer. Methods: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer during 2017 excluding nonmelanoma skin cancer. Diagnoses, medication, and contact with general practitioners in the exposure period (2007–2016) were considered for the predictive model. We applied backward selection to all variables by logistic regression to develop a risk model for cancer. We applied the models to the validation cohort, calculated the receiver operating characteristic curves, and estimated the corresponding areas under the curve (AUC). Results: The study population consisted of 4.2 million persons; 32,447 (0.76%) were diagnosed with cancer in 2017. We identified 39 predictive risk factors in women and 42 in men, with age above 30 as the strongest predictor for cancer. Testing the model for cancer risk showed modest accuracy, with an AUC of 0.82 (95% CI 0.81–0.82) for men and 0.75 (95% CI 0.74–0.75) for women. Conclusion: We have developed and tested a model for identifying the individual risk of cancer through the use of administrative data. The models need to be further investigated before being applied to clinical practice.

Fractures in patients with and without congenital heart disease – A nationwide register-based cohort study

BackgroundPatients with congenital heart disease (CHD) now live longer; thus, there is a need to assess factors related to ageing in this group. We aimed to determine the incidence and risk of fractures in patients with CHD. MethodsData of patients with CHD were retrieved from the National Swedish Patient Register (n = 83,084) and matched according to birth year and sex, with nearly nine controls per patient from the Total Population Register in Sweden (n = 719,447). CHD diagnoses were classified according to complexity, and fractures according to anatomical disposition. ResultsIn comparison with controls, lower incidence rate (IRs) per 10,000 person-years were found in male patients (7.59, 95% confidence interval [CI]: 6.92–8.31 vs. 9.29, 95% CI: 9.06–9.53) and female patients (5.73, 95% CI: 5.11–6.40 vs. 6.02, 95% CI: 5.83–6.23) aged 0–17 years with complex CHD. However, the IR of fractures for all patients with CHD was slightly higher than that of controls (7.42 vs. 7.06 per 10,000 person-years). Patients with CHD from the oldest age group (≥60 years) had a 21% increased risk of fractures in comparison with controls without CHD. ConclusionWe found that younger patients with complex CHD had a decreased risk of fractures compared with controls without CHD. In contrast, older patients with CHD showed a slightly increased risk of fractures. The increased risk of fractures, together with previous reports of decreased physical capacity, increasing age, and the sequent onset of osteoporosis, warrants close attention in the ageing population of patients with CHD.

Increased morbidity evaluated on hospital contacts and prescriptions among 100,834 Danish breast cancer survivors.

Cardiovascular disease competes with breast cancer (BC) as the leading cause of death for females diagnosed with breast cancer. Not much is known concerning morbidity and medicine use in the short and long term after a BC diagnosis. The aim of this study was to determine acute and long-term morbidity in Danish women treated for BC. A nationwide registry-based cohort study of 100,834 BC patients identified in the clinical database of Danish Breast Cancer Cooperative Group (DBCG) and 1,100,320 (10 per patient) age-matched Danish women without BC, serving as controls. Morbidity was studied using complete data on hospital contacts and medicinal use. The risk of hospital contacts was significantly increased in BC survivors compared with controls evaluated both by means of Cox regression and negative binomial regression analysis both during and after cessation of breast cancer treatment. Young age at breast cancer diagnosis was associated with the most pronounced increase in risk of hospital contacts, both during and after cessation of BC treatment. Medicinal use was significantly increased among BC patients compared to controls, both during (HR 1.27 (1.26-1.28), p < 0.0001) and after BC treatment (HR 1.18 (1.17-1.19), p < 0.0001, and present for all subgroups of medicine. Overall, BC survivors have a pronounced increase in hospital contacts and medicinal use compared to women without BC. Premenopausal status at BC diagnosis was associated with an overall higher excess morbidity and a higher burden both during and after treatment.

July 2022 Stroke Highlights.

July 2022 Stroke Highlights.

P-711 Differences in live birth results using donor or partner semen in single women, same-sex and different-sex couples. A Danish Nationwide register-based Cohort Study

Abstract Study question Are there any differences in the chance of a live birth using donor or partner semen in the different groups of women attending fertility clinics? Summary answer The chance of a live birth improves using donor semen for Intrauterine Insemination (IUI) treatments. No difference is observed for In Vitro Fertilization (IVF) treatments. What is known already Few studies regarding the efficacy of ART treatments using donor semen are available and most of them focus only on IUI treatments. Moreover, they usually do not take into account the different groups of women utilizing them or possible differences with the use of male partner semen. Study design, size, duration Danish nationwide cohort study based on health registers including all ART treatments from 2007 to 2017. The number of treatments in women using donor semen was 31540 for IUI and 7770 for IVF. For women using partner semen the number of treatments was 80949 for IUI and 74425 for IVF. ART treatments in women using donor semen were further subdivided into three groups based on women's relationship status: different-sex couples single women, and same-sex couples. Participants/materials, setting, methods Live birth chance per ART treatment cycle, IUI or IVF, using donor or partner semen has been assessed. In a subanalysis, the difference in a live birth was also evaluated comparing women using partner semen and women using donor semen stratified according to the partner with whom they attend the fertility clinics. The crude and confounders adjusted odds ratio (OR and aOR) were obtained by multilevel logistic regression. Main results and the role of chance A live birth was obtained in 13.9% of IUI treatments in women using donor semen compared to 12.3% in women using partner semen with an aOR of 1.33 (95% CI: 1.27-1.40). More in detail, for different groups of women using donor semen the aOR of live birth after IUI treatments was: aOR 1.48 (95% CI: 1.38-1.59) in women with male partners using donor semen, aOR 1.20 (95% CI: 1.13-1.28) in single women and aOR 1.46 (95% CI: 1.32-1.62) in women with female partners using donor semen. For what concern IVF treatments, 20.7% of treatments in women using donor semen and 25.7% of treatments in women using partner semen resulted in a live birth. The aOR was 0.99 (95% CI: 0.92-1.06). Moreover, for the different groups of women using donor semen compared to women using partner semen, the aOR of live birth after IVF treatments was: aOR 1.16 (95% CI: 1.02-1.32) in women with male partners using donor semen, aOR 0.88 (95% CI: 0.80-0.96) in single women, and aOR 1.20 (95% CI: 1.00-1.44), in women with female partners using donor semen. Limitations, reasons for caution Being an observational study, it is not possible to exclude the presence of unknown confounders or residual confounding which might affect the results. Wider implications of the findings This is one of the few studies assessing the ART success chances using donor or partner semen with attention to the now diverse population groups receiving ART treatments. We hope our results would be useful to healthcare professionals to better advise and help all women and couples attending fertility clinics Trial registration number not applicable

Toward Improving the Transition of Patients With Congenital Adrenal Hyperplasia From Pediatrics to Adult Healthcare in Japan

The transition of patients with childhood-onset chronic diseases from pediatric to adult healthcare systems has recently received significant attention. Since 2013, the Japan Pediatric Society developed working groups to formulate guidelines for transition of patients with childhood-onset chronic diseases from pediatric to their disease specialty. Herein, we report on the activities of the Japan Society of Pediatric Endocrinology (JSPE) and the current status of transition medicine for 21-hydroxylase deficiency (21-OHD) in Japan. The JSPE proposed roadmaps and checklists for transition and prepared surveys on the current status of healthcare transition for childhood-onset endocrine diseases. In Japan, newborn screening for 21-OHD started in January 1989; however, there is no nationwide registry-based longitudinal cohort study on 21-OHD from birth to adult. The current status and the whole picture of healthcare and health problems in adult patients with 21-OHD remain unclear. Thus, we conducted a questionnaire survey on JSPE members to clarify the current status of healthcare transition of 21-OHD and discuss future perspectives for the healthcare transition of patients with 21-OHD in Japan.

Use of hypnotics among women diagnosed with cervical cancer – A population-based cohort study

ObjectivePrevious studies suggest that sleeping problems are frequent after cervical cancer. However, the evidence on the use of hypnotics is sparse. We investigated if women diagnosed with cervical cancer have an increased risk of using hypnotics and identified risk factors for prolonged use. MethodsIn this nationwide register-based cohort study, 4264 women diagnosed with cervical cancer from 1997 to 2013 and 36,632 cancer-free women were followed in registers until 2016. Prolonged use of hypnotics was defined as more than three prescriptions with no more than three months in between. Data were analysed using Cox proportional hazards regression models and multistate Markov models separately for women with localized and advanced cervical cancer. ResultsThe rate of first use of hypnotics was substantially increased during the first year after cervical cancer diagnosis compared to cancer-free women (HRlocalized 4.4, 95% CI 3.9–5.1; HRadvanced 8.9, 95% CI 7.5–10.6) and remained markedly increased for up to five years after diagnosis. Dependent on stage of disease and age, 1.4 to 4.7 excess women per 100 with cervical cancer were prolonged users of hypnotics compared to cancer-free women one year after diagnosis. Risk factors for prolonged use of hypnotics were higher age, short education, previous use of antidepressants or anxiolytics, and advanced disease. ConclusionsWomen diagnosed with cervical cancer are at increased risk of prolonged use of hypnotics. For the majority, treatment with hypnotics is initiated within the first year after cancer diagnosis, but the rate of first use is increased for up to five years.

Association of maternal psoriasis and small for gestational age or preterm birth: a nationwide matched cohort study in 69 080 singleton infants.

Women with certain inflammatory diseases have an increased risk of giving birth to infants who are small for gestational age (SGA) or preterm birth (PTB), with maternal disease activity being the most important risk factor. However, previous studies investigating an association between psoriasis and SGA are scarce and have shown conflicting results. To investigate the association between maternal psoriasis and risk of SGA infants and PTB, respectively, both overall and stratified by psoriasis severity. This was a nationwide register-based matched cohort study of women with psoriasis matched 1 : 10 to women without psoriasis on age at delivery, body mass index and smoking status and with their first singleton infant born during the period 2004-2017. Odds ratio (OR) and 95% CI were calculated in conditional logistic regression models adjusted for known risk factors. From 516 063 deliveries, we identified 6282 women with psoriasis and 62 798 matched women without psoriasis. The risk of SGA and PTB was similar in women with psoriasis and matched controls: adjusted OR (aOR) = 1.07 (95% CI 0.98-1.17) and aOR = 1.05 (95% CI 0.93-1.19), respectively. The risk of term SGA was increased in women with psoriasis (aOR 1.11; 95% CI 1.01-1.22) compared with matched controls. Maternal psoriasis was not associated with increased risk of SGA or PTB. Risk of term SGA was slightly increased in women with a history of psoriasis compared with matched controls, however; these infants are likely to be constitutionally small with no increased risk of perinatal morbidity and mortality.

Risk prediction of 30-day mortality after stroke using machine learning: a nationwide registry-based cohort study

BackgroundsWe aimed to develop and validate machine learning (ML) models for 30-day stroke mortality for mortality risk stratification and as benchmarking models for quality improvement in stroke care.MethodsData from the UK Sentinel Stroke National Audit Program between 2013 to 2019 were used. Models were developed using XGBoost, Logistic Regression (LR), LR with elastic net with/without interaction terms using 80% randomly selected admissions from 2013 to 2018, validated on the 20% remaining admissions, and temporally validated on 2019 admissions. The models were developed with 30 variables. A reference model was developed using LR and 4 variables. Performances of all models was evaluated in terms of discrimination, calibration, reclassification, Brier scores and Decision-curves.ResultsIn total, 488,497 stroke patients with a 12.3% 30-day mortality rate were included in the analysis. In 2019 temporal validation set, XGBoost model obtained the lowest Brier score (0.069 (95% CI: 0.068–0.071)) and the highest area under the ROC curve (AUC) (0.895 (95% CI: 0.891–0.900)) which outperformed LR reference model by 0.04 AUC (p < 0.001) and LR with elastic net and interaction term model by 0.003 AUC (p < 0.001). All models were perfectly calibrated for low (< 5%) and moderate risk groups (5–15%) and ≈1% underestimation for high-risk groups (> 15%). The XGBoost model reclassified 1648 (8.1%) low-risk cases by the LR reference model as being moderate or high-risk and gained the most net benefit in decision curve analysis.ConclusionsAll models with 30 variables are potentially useful as benchmarking models in stroke-care quality improvement with ML slightly outperforming others.

Association of Celiac Disease and Inflammatory Bowel Disease: A Nationwide Register-Based Cohort Study

To determine the risk of inflammatory bowel disease (IBD) in patients with celiac disease (CeD) (and vice versa ) compared with general-population comparators. Using Swedish histopathology and healthcare register data, we identified 48,551 patients with CeD and 83,529 with IBD diagnosed in 1969-2016. Each patient was compared with age- and sex-matched general-population comparators (CeD: n = 240,136; IBD: n = 408,195). Cox regression estimated hazard ratios (HRs) for IBD in patients with CeD and vice versa . Our main analyses were limited to events beyond the first year of follow-up to reduce potential surveillance bias. During follow-up, 784 (1.6%) patients with CeD were diagnosed with IBD compared with 1,015 (0.4%) matched comparators. In patients with CeD, the HR for IBD was 3.91 (95% confidence interval [CI] 3.56-4.31), with largely similar HRs for Crohn's disease (4.36; 3.72-5.11) and ulcerative colitis (3.40; 3.00-3.85). During follow-up, 644 (0.8%) patients with IBD and 597 (0.1%) comparators were diagnosed with CeD. The HR for CeD in patients with IBD was 5.49 (95% CI 4.90-6.16), with the highest risk estimates seen in ulcerative colitis (HR = 6.99; 6.07-8.05), and the HR for Crohn's disease was 3.31 (2.69-4.06). In patients with CeD and IBD, the diagnostic interval was usually &lt;1 year; however, HRs of 3-4 were seen even after 10 years of follow-up. During 20 years of follow-up, 2.5% of patients with CeD developed incident IBD, and 1.3% of patients with IBD developed CeD. The bidirectional association between CeD diagnosis and IBD warrants attention in the initial assessment and follow-up of these conditions. Their co-occurrence, independent of temporal sequence, suggests shared etiology.

Thromboembolism and bleeding in patients with atrial fibrillation and liver disease – A nationwide register-based cohort study: Thromboembolism and bleeding in liver disease

BackgroundBalancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging. PurposeTo examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF. MethodsDanish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease. ResultsFour hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1–2 (2–3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22–2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45–0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status. ConclusionOral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease.

Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark

Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 × 107 person-years (women, 4.18 × 107 person-years; men, 4.04 × 107 person-years). The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5.0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P < .001). This study in Denmark provides nationwide empirical incidence of TED and strabismus and surgical interventions after TED that required inpatient or outpatient hospital treatment, and might be used for patient information and health care planning.

Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke

Reperfusion therapies (thrombolysis and thrombectomy) are of paramount importance for the recovery after ischemic stroke. We aimed to investigate if socioeconomic status (SES) was associated with the chance of receiving reperfusion therapy for ischemic stroke in a country with tax-funded health care. This nationwide register-based cohort study included patients with ischemic stroke registered in the Danish Stroke Registry between 2015 and 2018. SES was determined by prestroke educational attainment, income level, and employment status. Data on SES was obtained from Statistics Denmark and linked on an individual level with data from the Danish Stroke Registry. Risk ratios (RR) for receiving reperfusion therapies were calculated using univariate and multivariable Poisson regression with robust variance. A total of 37 187 ischemic stroke patients were included. Low SES, as defined by education, income and employment status, was associated with lower treatment rates. The socioeconomic gradient was most pronounced according to employment status, with intravenous thrombolysis rates of 23.7% versus 15.8%, and thrombectomy rates of 5.1% versus 2.8% for employed versus unemployed patients. When the analyses were restricted to patients with timely hospital arrival, and adjusted for age, sex and immigrant status, low SES according to income and employment remained unfavorable for the likelihood of receiving intravenous thrombolysis: adjusted RR, 0.90 (95% CI, 0.86-0.95) for low versus high income, and adjusted RR, 0.77 (95% CI, 0.71-0.84) for unemployed versus employed patients. Similarly, low SES according to income and employment status remained unfavorable for the likelihood of receiving thrombectomy: adjusted RR, 0.83 (95% CI, 0.72-0.95) for low versus high income and adjusted RR, 0.68 (95% CI, 0.53-0.88) for unemployed versus employed patients. Socioeconomic inequalities in reperfusion treatment rates among ischemic stroke patients prevail, even in a country with tax-funded universal health care.

Association Between Inflammatory Bowel Disease and Spondyloarthritis: Findings from a Nationwide Study in Sweden.

Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age. We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients. IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn's disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]). IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

MO439: Cardiovascular Mortality Among Persons With Advanced Chronic Kidney Disease: A Matched Cohort Study

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) and diabetes are both well-established risk factors for cardiovascular mortality. However, the risk of cardiovascular mortality and the impact of diabetes for those who have already reached advanced CKD are poorly examined. We examined the risk of cardiovascular mortality among persons with advanced CKD with and without diabetes. METHOD In a nationwide registry-based retrospective matched cohort study, we identified all Danish persons aged ≥ 18 years with advanced CKD between 2002 and 2018. Persons were included in the study at first measured estimated glomerular filtration rate (eGFR) &amp;lt; 30 mL/min/1.73 m2. We excluded persons having a major cardiovascular event or dying &amp;lt; 30 days after inclusion. Non-exposed persons with eGFR ≥ 30 mL/min/1.73m2 (with and without diabetes) were matched on birthyear and sex in a ratio of 4:1. By using the Danish Register of Medicinal Product Statistics, persons with diabetes were identified. Information regarding mortality was obtained from the Danish Registry of Causes of Death. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized absolute risk of cardiovascular mortality adjusted for age, sex and prior cardiovascular disease and subsequently stratified by age group (18–49, 50–59, 60–69, 70–79, 80 years or older). RESULTS We included 135 824 persons with advanced CKD. Overall, 52% were women and the mean age was 76 years. There were 31 991 (23.6%) with diabetes, of whom 2512 (7.9%) had type 1 diabetes. The mean duration of diabetes was 9.7 years. Figure 1 depicts the standardized absolute risk of cardiovascular mortality. Estimations stratified by age groups are shown in Table 1. For persons with diabetes, the standardized absolute risk (95% CI) of cardiovascular mortality was 13.4% (11.5–15.1) in persons aged 18–49 years 5 years after diagnosis, rising to 35.7% (34.7–36.6) in persons aged ≥ 80 years. Compared with age- and sex matched persons, the corresponding relative risk [95% confidence interval (CI)] was 38.0 (29.9–48.1) in persons aged 18–49 years, declining to 1.8 (1.7–1.8) in persons aged ≥ 80 years. Among persons without diabetes, the standardized absolute risk (95% CI) 5 years after diagnosis was 5.2% (4.5–5.8) in persons aged 18–49 years, rising to 33.6% (33.1–34.0) in persons aged ≥ 80 years. The corresponding relative risk was 14.6 (11.7–18.4) and 1.7 (1.6–1.7), respectively, compared with matched persons. Comparing persons with diabetes to persons without diabetes, the relative risk (95% CI) of cardiovascular mortality 5 years after diagnosis was 2.6 (2.2–3.2), 1.8 (1.6–2.9), 1.4 (1.3–1.5), 1.2 (1.1–1.2), 1.1 (1.0–1.1) for age group 18–49, 50–59, 60–69, 70–79, ≥80 years, respectively. CONCLUSION Persons with advanced CKD have, independently of age, a much higher risk of cardiovascular mortality compared with the background population and in the age groups ˂70 years this is even more outspoken in persons with concomitant diabetes. These data highlight the importance of early cardiovascular risk assessment for this population.