Danish Cohort Study Research Articles

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.

Use of non-recommended drugs in Brugada Syndrome: a Danish nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Background To lower the risk of sudden cardiac death, patients with Brugada Syndrome (BrS) are recommended to avoid intake of drugs known to increase the risk of arrhythmias or the development of type-1 BrS ECG. However, information on adherence to these recommendations among patients with BrS is limited. Purpose To examine treatment with non-recommended drugs before and after diagnosis with BrS, risk factors of treatment with these drugs, and whether treatment was associated with a higher risk of hospitalization with ventricular arrhythmias or death. Methods All patients diagnosed with BrS in Denmark (1995-2018) with &amp;gt;12 months of follow-up were identified through nationwide registries using the ICD-10 diagnosis code DI472M (PPV 95.8%). Relevant BrS risk drugs were identified and grouped as drugs to "avoid" or "preferably avoid" in agreement with the likelihood of promoting arrhythmias and type-1 BrS ECG according to brugadadrugs.org(1) (accessed August 2021). Multiple logistic regression (adjusted for sex, age, year of diagnosis, and relevant comorbidities and drugs) was performed to identify factors associated with risk drug use during follow-up. Results We identified 270 patients with BrS. Median age at the time of diagnosis was 46.2 years [IQR 32.6-57.6], 70.4% were male. Before the time of diagnosis, 16 patients (5.9%) were treated with a drug to "avoid" or "preferably avoid" (n=5 and n=12, respectively). During a median follow-up of 79 months, 89 patients (33%) were treated with at least one BrS risk drug after the time of diagnosis (table). A total of 22 patients with BrS (8.1%) received ≥2 different drugs at any time during follow-up. There was no significant difference in proportions of patients receiving a risk drug the year prior to diagnosis (12.2%) compared to each of the five years following diagnosis (year 1-5, respectively: 12.2%; 9.7%; 12.3%; 13.6%; 13.5% (p&amp;gt;0.05 for all)). Females had an odds ratio (OR) of 2.21 [95% CI 1.21-4.03] for use of risk drugs. Also associated with a greater likelihood of risk drug use after diagnosis were having a psychiatric disease at baseline (OR=4.80 [1.72-13.41]) and any use of a risk drug within 90 days prior to diagnosis (OR=8.54 [2.13-34.31]) (figure). During follow-up, six patients were hospitalized for ventricular arrhythmias; none had redeemed a prescription of a risk drug. In total, 12 patients died, of which five (41.7%) had redeemed a prescription of one or more risk drugs within 50 days of death. Conclusions 1/3 patients with BrS received a risk drug at any time point after diagnosis. No change in proportions of patients treated with risk drugs was identified after time of diagnosis. 5/12 patients that died during follow-up had redeemed a prescription of one or more risk drugs within 50 days of death. Female sex, any psychiatric diagnosis, and use of a non-recommended drug before diagnosis with BrS were associated with a greater likelihood of risk drug use after diagnosis.

Factors associated with risk and prognosis of intensive care unit admission in patients with acute leukemia: a Danish nationwide cohort study

Identifying risk factors for intensive care unit (ICU) admission in acute leukemia (AL) patients may guide decision-making and improve prognosis. We included all adult AL patients receiving high-intensive chemotherapy in Denmark from 2005 to 2016. We examined risk factors [crude and adjusted (a) relative risks (RRs) with 95% confidence intervals (CI)] and calculated RRs of death after 1-, 3-, and 5-years in ICU-admitted patients compared with matched cohorts. In 1417 AML and 306 ALL patients, the 1-year risk of ICU admission was 28.1% for AML and 26.4% for ALL patients, with the majority related to the first course of chemotherapy. Performance status >1 was associated with increased risk. The 1-year mortality was higher in ICU-admitted patients (AML: 69.7 vs. 35.0% [aRR 2.74;CI = 2.17–3.47]; ALL 65.0 vs. 20.0% [aRR 3.04;CI = 1.54–6.02]). The excess mortality decreased with time. In this study, performance status was associated with increased risk of ICU admission and identifies high-risk patients. ICU admission was associated with high mortality, especially within the first year.

Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study

Background/aimsAssociations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment...

Associations between single and combined occupational mechanical exposures and surgery for subacromial impingement syndrome: a nationwide Danish cohort study.

This study aimed to evaluate whether the risk of surgery for subacromial impingement syndrome (SIS) increases with the number of combined occupational mechanical exposures compared with single exposure. We reanalyzed data from a register-based cohort study of the entire Danish working population (N=2 374 403) with 14 118 events of surgery for SIS (2003-2008). Exposure information in 10-year windows was obtained by combining occupational codes with a job exposure matrix. For single and combined mechanical exposures, we created three exposure variables of the number of years with specific exposure intensities with or without co-existing mechanical exposures. We used logistic regression as survival analysis. We found exposure-response relations for duration and intensity of each single mechanical exposure except for repetition. The single effect of arm elevation >90º reached a maximum adjusted odds ratio (ORadj) of 1.7 [95% confidence interval (CI) 1.5-2.0], which increased to 1.8 (95% CI 1.5-2.0), 2.0 (95% CI 1.9-2.2), and 2.2 (95% CI 2.0-2.5) when combined with repetition, force, and both. When combining repetition with arm elevation >90º, force, and both, ORadj increased from 1.5 (95% CI 1.3-1.8) to 2.1 (95% CI 1.8-2.4), 2.5 (95% CI 2.4-2.9), and 2.7 (95% CI 2.4-3.0). For force, ORadj increased from 2.5 (95% CI 2.1-2.9) to 2.6 (95% CI 2.3-2.8), 2.8 (95% CI 2.4-3.2), and 3.0 (95% CI 2.6-3.4). We found an increased risk of surgery for SIS with the number of combined exposures; the risk was especially pronounced when the combined exposures included force.

Alemtuzumab induced thyroid disease: a Danish cohort study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SGLT2 inhibitor treatment does not increase risk of osteoporotic fractures compared to GLP-1 receptor agonists: a Danish population-based cohort study

SGLT2 inhibitor treatment does not increase risk of osteoporotic fractures compared to GLP-1 receptor agonists: a Danish population-based cohort study

Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study

BackgroundMultisystem inflammatory syndrome in children (MIS-C) occurs after infection with SARS-CoV-2 and its incidence is likely to depend on multiple factors, including the variant of the preceding SARS-CoV-2 infection and vaccine effectiveness. We aimed to estimate the incidence of MIS-C, and describe the clinical phenotype, following the delta variant of SARS-CoV-2 (B.1.617.2 and sublineages) according to vaccination status. We aimed to compare the incidence and clinical phenotype of MIS-C from our cohort during the pre-delta era.MethodsThis prospective, population-based cohort study included patients aged 0–17 years hospitalised with MIS-C in Denmark, according to the US Centers for Disease Control and Prevention case definition, from Aug 1, 2021, to Feb 1, 2022, a period dominated by the delta variant. We identified MIS-C cases via a nationwide research collaboration involving real-time data collection from all 18 paediatric departments. Aggregated number of SARS-CoV-2 infections by vaccination status was obtained from the Danish COVID-19 surveillance registries. The incidence of MIS-C was calculated using the estimated number of infected individuals by vaccination status. We calculated the incidence of MIS-C per 1 000 000 vaccinated and unvaccinated person-years, and estimated vaccine effectiveness as 1–incidence rate ratio using Poisson regression. Incidence and phenotype of MIS-C were compared with MIS-C cases from the first year of the pandemic. This study is registered at ClinicalTrials.gov, NCT05186597.FindingsWe identified 51 MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The incidence of MIS-C was one in 3400 unvaccinated individuals (95% CI 2600–4600) with the delta variant and one in 9900 vaccinated individuals (95% CI 1800–390 000) with breakthrough infection. The estimated vaccine effectiveness against MIS-C after the delta variant was 94% (95% CI 55–99; p=0·0061) in individuals aged 5–17 years. The clinical phenotype during the delta wave was comparable to the pre-delta era.InterpretationWe found the incidence and phenotype of MIS-C in unvaccinated children during the delta wave to be similar to the incidence during the first year of the pandemic. We found vaccine effectiveness to be high against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased incidence of MIS-C after breakthrough infection. Knowledge of the incidence of MIS-C after different SARS-CoV-2 variants and the effect of vaccination might contribute to the elucidation of the extent to which MIS-C is a vaccine-preventable disease.FundingNational Ministry of Higher Education and Science and Innovation Fund Denmark.

Increasing Incidence of Pouchitis Between 1996 and 2018: A Population-Based Danish Cohort Study

Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis. Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis. Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05). This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

Significant gender differences in clinical disease activity and severity of multiple sclerosis: a Danish nationwide cohort study (S40.005)

Significant gender differences in clinical disease activity and severity of multiple sclerosis: a Danish nationwide cohort study (S40.005)

Validation of MRI radiological reports in pediatric MS according to the McDonald 2017 criteria: A Danish nationwide multicenter cohort study (P13-4.007)

Validation of MRI radiological reports in pediatric MS according to the McDonald 2017 criteria: A Danish nationwide multicenter cohort study (P13-4.007)

PO-24: Incidence of venous thromboembolism following head and neck surgery stratified according to cancer: a Danish nation-wide cohort study

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PO-12: Risk of bleeding after surgery for colorectal cancer in type 2 diabetes patients: a Danish population-based cohort study

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OC-12: Stroke and risk of cancer: a Danish population-based cohort study

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PO-01: KRAS mutation in colorectal cancer and risk of venous thromboembolism: a Danish population-based cohort study

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Investigation of the potential association between the use of fluoxetine and occurrence of acute pancreatitis: a Danish register-based cohort study.

BackgroundThere is currently conflicting evidence of the association between the use of selective serotonin reuptake inhibitors (SSRIs) and acute pancreatitis. The SSRI fluoxetine has been suspected to be the driver of this serious outcome. Therefore, this study aims to investigate the potential association between fluoxetine use and the occurrence of acute pancreatitis.MethodsWe conducted a nationwide cohort study using Danish register-based data from 1996 to 2016. The exposed group were new users of fluoxetine (1-year washout). The control subjects were new users of citalopram or SSRIs, excluding fluoxetine. The outcome was an incident diagnosis of acute pancreatitis with a 5-year washout. We used an intention-to-treat approach following patients for a maximum of 6 months. Cox regression analyses were performed, estimating hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age/sex, comorbidities and co-medications, using propensity score adjustment and matching.ResultsIn the propensity score-matched analyses, 61 783 fluoxetine users were included. The incidence rates among users of fluoxetine and other SSRIs were 5.33 (3.05–8.66) and 5.36 (3.06–8.70) per 10 000 person-years, respectively. No increased risk of acute pancreatitis was identified following fluoxetine exposure compared with either citalopram [HR 1.00, 95% CI 0.50–2.00) or other SSRIs (0.76, 0.40–1.46).ConclusionsFluoxetine use was not associated with an increased risk of acute pancreatitis compared with citalopram or other SSRIs. The absolute risk of acute pancreatitis was low and did not vary between different SSRIs. Further research is needed to determine whether there is a class effect on the risk of acute pancreatitis.

Functional outcome and quality of life after transanal minimal invasive pouch surgery.

To investigate functional outcomes and quality of life (QoL) after restorative proctocolectomy (RPC) using transanal minimal invasive surgery (TAMIS). The study consists of two sub-studies. A cohort study comprised 98 consecutive patients, who underwent TAMIS RPC. These patients were the first at our department to undergo TAMIS RPC. We collected information about surgery, complications, postoperative morbidity and mortality ≤ 30days, and pouch problems. Patients were also invited to participate in a case-control study in which the patients would respond to three different questionnaires, the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short Form-36 General Health Questionnaire (SF-36), and questions from the Pouch Dysfunction Score. We compared the responding TAMIS RPC patients to a Danish national cohort (0-10years from RPC, n = 514) of patients having RPC between 1980 and 2010. We compared functional outcomes and QoL. Four (4%) of the TAMIS patients had an anastomotic leak; none of these required re-operation with removal of the pouch. Anastomotic leak was treated with antibiotics and drain. Out of the four leaks, only one ended up with a permanent stoma; all others had their stoma reversed successfully. The TAMIS patients had the same number of bowel movements as the patients in the Danish national cohort study. The same was seen with regard to incontinence. We had no conversions in our series of TAMIS procedures. The TAMIS technique shows acceptable outcomes, both in regard to postoperative complications and also functional outcome and QoL.

Are 5-level triage systems improved by using a symptom based approach?\u2014a Danish cohort study

BackgroundFive-level triage systems are being utilized in Danish emergency departments with and without the use of presenting symptoms. The aim of this study was to validate and compare two 5-level triage systems used in Danish emergency departments: “Danish Emergency Process Triage” (DEPT) based on a combination of vital signs and presenting symptoms and a locally adapted version of DEPT (VITAL-TRIAGE) using vital signs only.MethodsThis was a retrospective cohort using data from five Danish emergency departments. All patients attending an emergency department during the period of 1 April 2012 until 31 December 2015 were included. Validity of the two triage systems was assessed by comparing urgency categories determined by each triage system with critical outcomes: admission to Intensive care unit (ICU) within 24 h, 2-day mortality, diagnosis of critical illness, surgery within 48 h, discharge within 4 h and length of hospital stay.ResultsWe included 632,196 ED contacts. Sensitivity for 24-h ICU admission was 0.79 (95% confidence interval 0.78–0.80) for DEPT and 0.44 (0.41–0.47) for VITAL-TRIAGE. The sensitivity for 2-day mortality was 0.69 (0.67–0.70) for DEPT and 0.37 (0.34–0.41) for VITAL-TRIAGE. The sensitivity to detect diagnoses of critical illness was 0.48 (0.47–0.50) for DEPT and 0.09 (0.08–0.10) for VITAL-TRIAGE. The sensitivity for predicting surgery within 48 h was 0.30 (0.30–0.31) in DEPT and 0.04 (0.04–0.04) in VITAL-TRIAGE. Length of stay was longer in VITAL-TRIAGE than DEPT. The sensitivity of DEPT to predict patients discharged within 4 h was 0.91 (0.91–0.92) while VITAL-TRIAGE was higher at 0.99 (0.99–0.99). The odds ratio for 24-h ICU admission and 2-day mortality was increased in high-urgency categories of both triage systems compared to low-urgency categories.ConclusionsHigh urgency categories in both triage systems are correlated with adverse outcomes. The inclusion of presenting symptoms in a modern 5-level triage system led to significantly higher sensitivity measures for the ability to predict outcomes related to patient urgency. DEPT achieves equal prognostic performance as other widespread 5-level triage systems.

The use of tourniquet in primary total knee arthroplasty does not increase the risk of venous thromboembolism within 90days of surgery: a Danish nationwide cohort study of 19,804 patients.

Existing evidence estimates a twofold risk of venous thromboembolisms (VTEs) if tourniquet is applied during total knee arthroplasties (TKAs). However, this estimate relies on multiple trials with a low number of patients analyzing VTEs as a secondary outcome. We hypothesized that tourniquet-use increases the risk of symptomatic VTE within 90days of contemporary primary TKA and aimed to use the extensive Danish healthcare registries to quantify this risk. Prospectively collected registry data from Danish patients receiving primary TKAs between 2014 and 2018 were included in the study. Patients were divided by tourniquet-use during surgery. By merging information from four nationwide registries, the study included 44 baseline characteristics with the potential to confound the association between tourniquet-use and VTE. Incidence rate and odds ratios were used to compare the risk of VTE within 90days of surgery. 19,804 patients of whom 10,111 (51%) were operated with tourniquet and 9693 (49%) without were included. The mean age (SD) was 70 (9) in both groups and 62% were females in the tourniquet group compared with 61% in the no tourniquet group. The groups were similarly comparable across all other baseline characteristics except type of post-operative thromboprophylaxis, type of anaesthesia, implant fixation, and year of surgery. The 90-days incidence of VTE was 0.77% (95% CI 0.60-0.94) in the tourniquet group compared with 1.10% (95% CI 0.90-1.31) in the no tourniquet group. Following adjustment for the unbalanced confounders, the odds ratio for VTE was 0.77 (95% CI 0.54-1.10) associated with tourniquet-use. In contemporary TKAs the rate of VTE within 90days is low and not significant altered by tourniquet-use. Thus, tourniquet can safely be applied during primary TKA-surgery without jeopardizing the risk of postoperative VTE. II-prospective cohort study.

Women with obesity participate less in cervical cancer screening and are more likely to have unsatisfactory smears: Results from a nationwide Danish cohort study

Some studies found an association between obesity and increased cervical cancer risk, but potential mechanisms are unknown. In this nationwide register-based cohort study, we investigated the association between overweight/obesity and cervical cancer screening participation and risk of unsatisfactory smears. The study population was identified in the Danish Medical Birth Registry. We included 342,526 women aged 23–49 years with pre-pregnancy body mass index (BMI) registered during 2004–2013. Screening participation and unsatisfactory smears during up to four years after child birth were identified in a nationwide pathology register. We used absolute risk regression to estimate the relative absolute risk (RAR) with 95% confidence intervals (CIs) of screening participation according to BMI, adjusted for age, calendar year, sociodemographic characteristics, parity and previous high-grade cervical intraepithelial neoplasia. Among those who were screened (n = 295,482), we used log-binomial regression to investigate the relative risk (RR) of an unsatisfactory smear according to BMI, adjusted for age, year, parity, oral contraceptive use and pathology department. A lower proportion of obese women (79.3%) than women of normal weight (85.8%) were screened, and obese women had lower adjusted probability of being screened than women of normal weight (RARadjusted = 0.94, 95% CI, 0.93–0.95). A higher proportion of obese women (2.4%) than women of normal weight (1.7%) had an unsatisfactory smear, and this association remained after adjustments (RRadjusted = 1.28, 95% CI, 1.19–1.38). In conclusion, women with obesity were less likely to participate in cervical cancer screening and more likely to have an unsatisfactory smear than women of normal weight.