Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

BACKGROUND: Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. METHODS: All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. RESULTS: In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn's disease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD: IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. CONCLUSION: The clinical course of CD is milder for those who have previously undergone appendectomy.

In a large nationwide cohort study, patients with Crohn's disease who underwent appendectomy had a milder clinical course than those without appendectomy.

Enhancing the data capture of periprosthetic joint infections in the Danish Knee Arthroplasty Registry: validity assessment and incidence estimation.

BACKGROUND AND PURPOSE: Revisions due to periprosthetic joint infection (PJI) are underestimated in national arthroplasty registries. Our primary objective was to assess the validity in the Danish Knee Arthroplasty Register (DKR) of revisions performed due to PJI against the Healthcare-Associated Infections Database (HAIBA). The secondary aim was to describe the cumulative incidences of revision due to PJI within 1 year of primary total knee arthroplasty (TKA) according to the DKR, HAIBA, and DKR/HAIBA combined. METHODS: This longitudinal observational cohort study included 56,305 primary TKAs (2010-2018), reported in both the DKR and HAIBA. In the DKR, revision performed due to PJI was based on pre- and intraoperative assessment disclosed by the surgeon immediately after surgery. In HAIBA, PJI was identified from knee-related revision procedures coinciding with 2 biopsies with identical microbiological pathogens. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of revision due to PJI in the DKR (vs. HAIBA, within 1 year of TKA) with 95% confidence intervals (CI). Cumulative incidences were calculated using the Kaplan-Meier method. RESULTS: The DKR's sensitivity for PJI revision was 58% (CI 53-62) and varied by TKA year (41%-68%) and prosthetic type (31% for monoblock; 63% for modular). The specificity was 99.8% (CI 99.7-99.8), PPV 64% (CI 62-72), and NPV 99.6% (CI 99.6-99.7). 80% of PJI cases not captured by the DKR were caused by non-reporting rather than misclassification. 33% of PJI cases in the DKR or HAIBA were culture-negative. Considering potential misclassifications, the best-case sensitivity was 64%. The cumulative incidences of PJI were 0.8% in the DKR, 0.9% in HAIBA, and 1.1% when combining data. CONCLUSION: The sensitivity of revision due to PJI in the DKR was 58%. The cumulative incidence of PJI within 1 year after TKA was highest (1.1%) when combining the DKR and HAIBA, showing that incorporating microbiology data into arthroplasty registries can enhance PJI validity.

Risk of cardiovascular disease after hospital-diagnosed overweight or obesity.

Objective: The aim was to examine the association between hospital-diagnosed overweight/obesity and incident CVD according to the time period of the overweight/obesity diagnosis. Design: This is a cohort study. Methods: From Danish national health registries, we identified all residents with a first-time hospital-based overweight/obesity diagnosis code, 1977-2018 (n = 195,221), and an age and sex-matched general population comparison cohort (n = 1,952,210). We computed adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression. We adjusted for comorbidities and educational level and applied 10 years of follow-up. Results: The overall incidence rate was 10.1 (95% CI 10.0-10.1) per 1000 person-years for the comparison cohort and 25.1 (95% CI 24.8-25.4) per 1000 person-years for the overweight/obesity cohort, corresponding to an aHR of 2.5 (95% CI 2.4-2.5). The aHR was elevated for all subtypes of CVD: heart failure: 3.9 (95% CI 3.7-4.1), bradyarrhythmia: 2.9 (95% CI 2.7-3.1), angina pectoris: 2.7 (95% CI 2.7-2.8), atrial fibrillation or flutter: 2.6 (95% CI 2.5-2.6), acute myocardial infarction: 2.4 (95% CI 2.3-2.4), revascularization procedure: 2.4 (95% CI 2.2-2.5), valvular heart disease: 1.7 (95% CI 1.6-1.8), ischemic stroke: 1.6 (95% CI 1.4-1.7), transient ischemic attack: 1.6 (95% CI 1.5-1.7), and cardiovascular death: 1.6 (95% CI 1.5-1.6). The 1-10-year aHR of any CVD associated with an overweight/obesity diagnosis decreased from 2.8 (95% CI 2.7-2.9) in 1977-1987 to 1.8 (95% CI 1.8-1.9) in 2008-2018. Conclusion: Patients with hospital-diagnosed overweight/obesity had high rates of ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and death, although the strength of the association decreased in recent years. Significance statement: Obesity is linked to metabolic abnormalities that predispose individuals to an increased risk of subtypes of CVD. In this population-based nationwide 40-year cohort study, we found that of 195,221 patients with an overweight/obesity diagnosis, more than 31,000 (15.9%) were admitted to hospital within 10 years because of CVD; corresponding to a 2.5-fold greater relative risk of any CVD associated with overweight/obesity than in the general population. We observed an increased risk for most CVD subtypes, including ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and cardiovascular death, although the strength of the association decreased in recent years. Our study emphasizes the importance of improved clinical handling of obesity and underscores the need to prevent associated complications to alleviate the burden of obesity.

Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study.

BACKGROUND: The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. OBJECTIVES: To develop and validate a prediction model for 90-day VTE risk. METHODS: A multinational cohort study was performed. For model development, records were used from the Oxford Royal College of General Practitioners Research and Surveillance Centre linked to Hospital Episode Statistics and Office of National Statistics UK routine data. For external validation, data were used from the Danish Hip and Knee Arthroplasty Registry, the National Patient Registry, and the National Prescription Registry. Binary multivariable logistic regression techniques were used for development. RESULTS: In the UK data set, 64 032 THA/TKA procedures were performed and 1.4% developed VTE. The prediction model consisted of age, body mass index, sex, cystitis within 1 year before surgery, history of phlebitis, history of VTE, presence of varicose veins, presence of asthma, history of transient ischemic attack, history of myocardial infarction, presence of hypertension and THA or TKA. The area under the curve of the model was 0.65 (95% CI, 0.63-0.67). Furthermore, 36 169 procedures were performed in the Danish cohort, of whom 1.0% developed VTE. Here, the area under the curve was 0.64 (95% CI, 0.61-0.67). The calibration slope was 0.92 in the validation study and 1.00 in the development study. CONCLUSION: This clinical prediction model for 90-day VTE risk following THA and TKA performed well in both development and validation data. This model can be used to estimate an individual's risk for VTE following THA/TKA.

Appendectomy and Risk of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study.

BACKGROUND: The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. RESULTS: We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohn's disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. CONCLUSIONS: Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN.

Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study.

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure.Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors.Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16).Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.

Fracture Rates in Children with Cerebral Palsy: A Danish, Nationwide Register-Based Study.

Background: In children with cerebral palsy (CP), fracture rates have been reported to be higher than in the general population but age-specific fracture rates have not been directly compared and the effect of comorbid epilepsy needs elucidation. This impairs decision-making regarding bone health interventions. Aim: We aimed to establish the age-specific fracture rates in children with CP with and without epilepsy in Denmark. Materials and Methods: Data from Danish registers were combined to establish cohorts of children with and without CP born in Denmark from 1997 to 2007. Fracture rates were calculated for 1997-2016. Results: We identified 1,451 children with CP and 787,159 without CP. Female/male fracture rates per 1,000 person-years were 23/27 with CP and 23/29 without CP. Male sex, epilepsy and anti-seizure medication, but not the diagnosis of CP or GMFCS-level, were associated with higher fracture rates. Relatively more lower extremity fractures occurred in non-ambulant children with CP. Interpretation/Conclusion: We found no increased fracture rates in children with CP when compared to peers; however, fracture locations suggested bone fragility in non-ambulant children. All children with epilepsy and on anti-seizure medication had increased fracture rates. We suggest bone health optimization in these groups.