Studies have highlighted the potential importance of modeling interactions for suicide attempt prediction. This case-cohort study identified risk factors for suicide attempts among persons with depression in Denmark using statistical approaches that do (random forests) or do not (least absolute shrinkage and selection operator regression [LASSO]) model interactions. Cases made a nonfatal suicide attempt (n = 6032) between 1995 and 2015. The comparison subcohort was a 5% random sample of all persons in Denmark on January 1, 1995 (n = 11 963). We used random forests and LASSO for sex-stratified prediction of suicide attempts from demographic variables, psychiatric and somatic diagnoses, and treatments. Poisonings, psychiatric disorders, and medications were important predictors for both sexes. Area under the receiver-operating characteristic curve (AUC) values were higher in LASSO models (in men, 0.85, 95% CI, 0.84-0.86; in women, 0.89, 95% C, 0.88-0.90) than random forests (in men, 0.76, 95% CI, 0.74-0.78; in women, 0.79, 95% CI = 0.78-0.81). Automatic detection of interactions via random forests did not result in better model performance than LASSO models that did not model interactions. Due to the complex nature of psychiatric comorbidity and suicide, modeling interactions may not always be the optimal statistical approach to enhancing suicide attempt prediction in high-risk samples.This article is part of a Special Collection on Mental Health.

Aim: A laparoscopic approach to total colectomy (TC) for inflammatory bowel disease (IBD) is being increasingly used, but data on its comparative benefits over open TC are conflicting. The aim of this study was to examine 90-day outcomes following laparoscopic and open TC for IBD in a nationwide cohort after the introduction of laparoscopy.Method: IBD patients undergoing TC in Denmark from 2005 to 2017 were identified from the Danish National Patient Registry. We used Kaplan-Meier methodology to estimate mortality and Cox regression analysis to estimate adjusted mortality rate ratios (aMRRs) and adjusted hazard ratios (aHRs) of reoperation, readmission and intensive care unit (ICU) transfer, comparing patients undergoing laparoscopic versus open TC.Results: We identified 1095 patients undergoing laparoscopic TC and 1523 patients undergoing open TC. Following emergency TC, 90-day mortality was 2.8% (1.6%-4.9%) after laparoscopic TC and 9.1% (7.0%-11.8%) after open TC. Ninety-day mortality was 0.9% (0.3%-2.5%) after laparoscopic TC and 2.6% (1.5%-4.3%) after open elective TC. The aMRRs associated with laparoscopic TC were 0.45 (95% CI 0.25-0.80) in emergency cases and 0.29 (95% CI 0.10-0.86) in elective cases. Risks of readmission were comparable following laparoscopic versus open TC, both in emergency [aHR = 0.93 (95% CI 0.76-1.15)] and elective [aHR = 0.83 (95% CI 0.68-1.02)] cases, while risks of ICU transfer and reoperation were lower following laparoscopic TC, both in emergency cases [aHR = 0.53 (95% CI 0.35-0.82) and aHR = 0.26 (95% CI 0.15-0.47)] and elective [aHR = 0.58 (95% CI 0.35-0.95) and aHR = 0.37 (95% CI 0.21-0.66)] cases.Conclusion: The introduction of laparoscopic TC for IBD in Denmark was not associated with increased mortality or morbidity. In fact, laparoscopic TC for IBD may be associated with lower short-term mortality and morbidity compared with open TC.

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Introduction: Cancer may increase the risk of bleeding. However, whether subdural hematoma is a marker of occult cancer remains unknown. We examined the association between non-traumatic subdural hematoma and cancer risk in a cohort study.Materials and Methods: Using Danish nationwide health registries, we identified 2713 patients with non-traumatic subdural hematoma and no previous cancer diagnosis, who were hospitalized between April 1, 1996 and December 31, 2019. We computed age-, sex-, and calendar year-standardized incidence ratios (SIRs) as the ratio of the observed to expected number of patients with cancer by using national incidence rates as reference as a measure of relative risk.Results: We identified 77 cancer cases within the first year of follow-up and 272 cancer cases thereafter. The one-year risk of cancer was 2.8% (95% confidence interval: 2.2-3.5), and the one-year SIR was 1.7 (95% confidence interval: 1.3-2.1). During the subsequent years, the SIR was 1.0 (95% confidence interval: 0.9-1.1). The relative risk was elevated for some hematological and liver cancers.Conclusion: The risk of a new cancer diagnosis was clearly increased in patients with non-traumatic subdural hematoma compared with the general population during the first year of follow-up. However, the absolute risk was low, thus limiting the clinical relevance of pursuing early cancer detection in these patients.

British Journal of DermatologyAccepted Articles RESEARCH LETTER Risk of Cancer in Patients with Psoriasis and Venous Thromboembolism: a Danish Population-based Cohort study 1996-2018 Sissel T. Sørensen, Corresponding Author Sissel T. Sørensen sts@clin.au.dk Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Correspondence Sissel T. Soerensen Email: sts@clin.au.dkSearch for more papers by this authorDavid Nagy, David Nagy Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Data curation (lead), Formal analysis (lead), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorLise Maria Lindahl, Lise Maria Lindahl Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Formal analysis (supporting), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorDóra K. Farkas, Dóra K. Farkas Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (equal), Data curation (lead), Formal analysis (equal), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorFrederikke S. Troelsen, Frederikke S. Troelsen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Methodology (supporting), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this author Sissel T. Sørensen, Corresponding Author Sissel T. Sørensen sts@clin.au.dk Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Correspondence Sissel T. Soerensen Email: sts@clin.au.dkSearch for more papers by this authorDavid Nagy, David Nagy Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Data curation (lead), Formal analysis (lead), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorLise Maria Lindahl, Lise Maria Lindahl Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Formal analysis (supporting), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorDóra K. Farkas, Dóra K. Farkas Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (equal), Data curation (lead), Formal analysis (equal), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this authorFrederikke S. Troelsen, Frederikke S. Troelsen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Contribution: Conceptualization (supporting), Methodology (supporting), Supervision (supporting), Writing - review & editing (supporting)Search for more papers by this author First published: 18 January 2022 https://doi.org/10.1111/bjd.21016 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/bjd.21016 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

BACKGROUND:Previous studies of the effect of interaction between psychiatric disorders on suicide have reported mixed results. We investigated the joint effect of depression and various comorbid psychiatric disorders on suicide. METHODS:We conducted a population-based case-cohort study with all suicide deaths occurring between 1 January 1995 and 31 December 2015 in Denmark (n = 14,103) and a comparison subcohort comprised of a 5% random sample of the source population at baseline (n = 265,183). We quantified the joint effect of pairwise combinations of depression and major psychiatric disorders (e.g., organic disorders, substance use disorders, schizophrenia, bipolar disorder, neurotic disorders, eating disorders, personality disorders, intellectual disabilities, developmental disorders, and behavioral disorders) on suicide using marginal structural models and calculated the relative excess risk due to interaction. We assessed for the presence of competing antagonism for negative relative excess risk due to interactions. RESULTS:All combinations of depression and comorbid psychiatric disorders were associated with increased suicide risk. For example, the rate of suicide among men with depression and neurotic disorders was 20 times (95% CI = 15, 26) the rate in men with neither disorder. Most disorder combinations were associated with subadditive suicide risk, and there was evidence of competing antagonism in most of these cases. CONCLUSIONS:Subadditivity may be explained by competing antagonism. When both depression and a comorbid psychiatric disorder are present, they may compete to cause the outcome such that having 2 disorders may be no worse than having a single disorder with respect to suicide risk.

Background Aspirin may reduce the risk of cancer, particularly gastrointestinal cancer, and venous thromboembolism (VTE). VTE can be the first symptom of occult cancer, but whether it is also a marker of occult cancer in aspirin users remains unknown. Therefore, we investigated the risk of cancer subsequent to VTE among users of low-dose aspirin. Methods We conducted a population-based cohort study using data from Danish health registries for the years 2001 to 2018. We identified all patients with a first-time diagnosis of VTE who also redeemed a prescription for low-dose aspirin (75-150mg) within 90 days prior to the first-time VTE. We categorized aspirin users by the number of prescriptions filled as new users (<5 prescriptions), short-term users (5-19 prescriptions), and long-term users (>19 prescriptions). We computed the absolute cancer risks and standardized incidence ratios (SIRs) for cancer using national cancer incidence rates. Results We followed-up 11,759 users of low-dose aspirin with VTE. Long-term users comprised 50% of aspirin users. The 1-year absolute risk of cancer was 6.0% for new users and 6.7% for short-term and long-term users, with corresponding SIRs of 3.3 (95% confidence interval [CI]: 2.8-4.0), 3.2 (95% CI: 2.9-3.7), and 2.8 (95% CI: 2.6-3.2), respectively. After the first year of follow-up, the SIR decreased to 1.2 (95% CI: 1.1-1.4) for new users, 1.1 (95% CI: 1.1-1.3) for short-term users, and 1.1 (95% CI: 1.0-1.2) for long-term users. Conclusion VTE may be a harbinger of cancer, even in users of low-dose aspirin, regardless of duration of use.

BACKGROUND:Accurate identification of persons at risk of suicide is challenging because suicide is a rare outcome with a multifactorial origin. The purpose of this study was to predict suicide among persons with depression using machine learning methods. METHODS:A case-cohort study was conducted in Denmark between January 1, 1995 and December 31, 2015. Cases were all persons who died by suicide and had an incident depression diagnosis in Denmark (n = 2,774). The comparison subcohort was a 5% random sample of all individuals in Denmark at baseline, restricted to persons with an incident depression diagnosis during the study period (n = 11,963). Classification trees and random forests were used to predict suicide. RESULTS:In men with depression, there was a high risk of suicide among those who were prescribed other analgesics and antipyretics (i.e., non-opioid analgesics such as acetaminophen), prescribed hypnotics and sedatives, and diagnosed with a poisoning (n = 96; risk = 81%). In women with depression, there was an elevated risk of suicide among those who were prescribed other analgesics and antipyretics, anxiolytics, and hypnotics and sedatives, but were not diagnosed with poisoning nor cerebrovascular diseases (n = 338; risk = 58%). DISCUSSION:Psychiatric disorders and their associated medications were strongly indicative of suicide risk. Notably, anti-inflammatory medications (e.g., acetaminophen) prescriptions, which are used to treat chronic pain and illnesses, were associated with suicide risk in persons with depression. Machine learning may advance our ability to predict suicide deaths.

Background: Previous studies of the effect of interaction between psychiatric disorders on suicide have reported mixed results. We investigated the joint effect of depression and various comorbid psychiatric disorders on suicide. Methods: We conducted a population-based case–cohort study with all suicide deaths occurring between 1 January 1995 and 31 December 2015 in Denmark (n = 14,103) and a comparison subcohort comprised of a 5% random sample of the source population at baseline (n = 265,183). We quantified the joint effect of pairwise combinations of depression and major psychiatric disorders (e.g., organic disorders, substance use disorders, schizophrenia, bipolar disorder, neurotic disorders, eating disorders, personality disorders, intellectual disabilities, developmental disorders, and behavioral disorders) on suicide using marginal structural models and calculated the relative excess risk due to interaction. We assessed for the presence of competing antagonism for negative relative excess risk due to interactions. Results: All combinations of depression and comorbid psychiatric disorders were associated with increased suicide risk. For example, the rate of suicide among men with depression and neurotic disorders was 20 times (95% CI = 15, 26) the rate in men with neither disorder. Most disorder combinations were associated with subadditive suicide risk, and there was evidence of competing antagonism in most of these cases. Conclusions: Subadditivity may be explained by competing antagonism. When both depression and a comorbid psychiatric disorder are present, they may compete to cause the outcome such that having 2 disorders may be no worse than having a single disorder with respect to suicide risk.

Background: Venous thromboembolism (VTE) may be the first manifestation of occult cancer. Dementia has been linked to reduced cancer risk. Objective: We examined the risk of cancer following VTE in people with dementia in comparison to the risk in the general population. Methods: We conducted a population-based Danish registry-based cohort study following patients with a first-time VTE and a previous or concurrent diagnosis of dementia during the period 1 April 1996 –31 December 2017. We followed the study participants from date of VTE until diagnosis of cancer, death, emigration, or end of study period, whichever came first. The absolute risk of cancer within one year after VTE was computed, treating death as a competing risk. We calculated gender, age, and calendar-period standardized incidence ratios (SIRs) of cancer based on national cancer rates. Results: We followed 3,552 people with dementia and VTE for a median of 1.3 years. Within the first year after VTE, they had a 90% increased risk of cancer in comparison with the general population [SIR: 1.9 (95% confidence interval: 1.6–2.4)]. During subsequent follow-up years, the SIR fell to 0.7 (95% confidence interval: 0.5–0.8). Findings for Alzheimer’s disease and VTE were similar. Conclusion: People with dementia have an increased risk of a cancer diagnosis during the first year following VTE, perhaps related to increased surveillance, and a lower risk thereafter. Overall risk is similar to that of the general population.

Background Venous thromboembolism (VTE) may be the first symptom of cancer. Statins are suggested to prevent VTE, but the risk of cancer in VTE patients using statins remains poorly understood. Objectives To examine if VTE is a marker of cancer in users of statins. Methods We identified all Danish patients during 1996–2017 with a first-time diagnosis of VTE and a filled prescription for a statin within 90 days prior to the VTE diagnosis. We classified patients as prevalent users if the first filling of a statin occurred more than one year preceding the VTE diagnosis, and as new users if the first filling occurred within the preceding year. We computed cumulative incidences of cancer, with death as a competing risk, and age-, sex-, and calendar-period standardized incidence ratios (SIRs), comparing the observed cancer incidence with the expected based on national cancer statistics. Results Among 9280 (85%) prevalent users of statin and 1580 (15%) new users, the one-year cumulative incidence of any cancer was 6.6 (95% CI: 6.1–7.2) for prevalent users and 6.4 (95% CI: 5.2–7.6) for new users; the corresponding SIRs were 3.1 (95% CI: 2.9–3.3) and 3.5 (95% CI: 2.9–4.3). In the second and subsequent years, the SIRs diminished and approached unity for both prevalent (1.1 [95% CI: 1.1–1.2]) and new users (1.1 [95% CI: 0.9–1.3]). Conclusions VTE patients using statins had a 3-fold increased rate of cancer in the first year after diagnosis. A first VTE serves as an important marker of cancer, regardless of statin use.