Healthcare resource utilization in patients with myeloproliferative neoplasms: A Danish nationwide matched cohort study.

Few studies have assessed healthcare resource utilization (HRU) in patients with Philadelphia-negative myeloproliferative neoplasms (MPN) using a matched cohort design. Further, no detailed assessment of HRU in the years preceding an MPN diagnosis exists. We conducted a registry-based nationwide Danish cohort study, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN diagnosed between January 2010 and December 2016. HRU data were summarized annually from 2 years before MPN diagnosis until emigration, death, or end of study (December 2017). We included 3342 MPN patients and 32 737 comparisons without an MPN diagnosis, matched on sex, age, region of residence, and level of education. During the study period, the difference in HRU (rate ratio) between patients and matched comparisons ranged from 1.0 to 1.5 for general practitioner contacts, 0.9 to 2.2 for hospitalizations, 0.9 to 3.8 for inpatient days, 1.0 to 4.0 for outpatient visits, 1.3 to 2.1 for emergency department visits, and 1.0 to 4.1 for treatments/examinations. In conclusion, MPN patients had overall higher HRU than the matched comparisons throughout the follow-up period (maximum 8 years). Further, MPN patients had substantially increased HRU in both the primary and secondary healthcare sector in the 2 years preceding the diagnosis.

Cardiovascular risk and mortality in rheumatoid arthritis compared with diabetes mellitus and the general population.

OBJECTIVES: To compare risk of cardiovascular disease and mortality in patients with incident RA, diabetes mellitus (DM) and the general population (GP). METHODS: Patients diagnosed with incident RA were matched 1:5 by age, sex and year of RA diagnosis with the GP. In the same period, patients with incident DM were included. Outcomes were heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, major adverse cardiovascular events (MACE) and death up to 10 years after diagnosis. RESULTS: We included 15 032 patients with incident RA, 301 246 patients with DM and 75 160 persons from the GP. RA patients had an increased risk of HF [hazard ratio (HR) 1.51, 95% CI: 1.38, 1.64], MI (HR 1.58, 95% CI: 1.43, 1.74), percutaneous coronary intervention (PCI; HR 1.44, 95% CI: 1.27, 1.62), coronary artery bypass grafting (CABG; HR 1.30, 95% CI: 1.05, 1.62) and stroke (HR 1.22, 95% CI: 1.12-1.33) compared with the GP. However, the 10-year all-cause mortality was at the same level as observed in the GP. Cardiac death and MACE were increased in RA compared with the GP. When compared with patients with DM, RA patients had a lower adjusted risk of HF (HR 0.79, 95% CI: 0.73, 0.85), CABG (HR 0.62, 95% CI: 0.51, 0.76) and stroke (HR 0.82, 95% CI: 0.76, 0.89), and similar risk of MI and PCI. DM patients had the highest risk of 10-year mortality, cardiac death and MACE. CONCLUSION: This study demonstrates that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.

Platelet counts of adults upon acute hospital admission to internal medicine units are a predictor of mortality.

The objective of this cohort study was to examine the association between platelet counts upon acute hospitalization and mortality. The study included all adults in North and Central Denmark Regions with a first acute admission to an internal medicine unit during 2006-2012, categorized by first platelet count within +/-24 hours of admission. We assessed the association between platelet count and in-hospital, 30-day, 90-day, and 365-day mortality using age- and sex-adjusted Cox models. We also stratified analyses by presence/absence of comorbidity and performed additional analyses restricted to patients with a primary discharge diagnosis of cardiovascular disease or infection. Among the 274,148 study patients, the 1-year mortality was 12.6%. The association between platelet count and mortality took the form of an asymmetric U-shaped curve. For 30-day mortality, hazard ratios (HRs) were 5.24 (95% CI: 4.60-5.97) for platelet count < 50 × 109/L and 2.50 (95% CI: 2.33-2.69) for platelet count ≥ 500 × 109/L, compared with a normal platelet count (150-400 × 109/L). A slightly increased risk of mortality was observed for platelet counts < 200 × 109/L and ≥ 250 × 109/L. A similar pattern was observed for 30-day, 90-day, and 365-day mortality and in all subgroups except patients with a primary discharge diagnosis of infection. In this case, patients with a platelet count between 150 × 109/L and 199 × 109/L had the lowest mortality. Platelet counts in adults upon acute hospital admission to internal medicine units, including counts within the normal range, are a predictor of mortality.

Risk of Arterial Thromboembolism, Venous Thromboembolism, and Bleeding in Patients with Nephrotic Syndrome: A Population-Based Cohort Study.

BACKGROUND: Although venous thromboembolism is a well-known complication of nephrotic syndrome, the long-term absolute and relative risks of arterial thromboembolism, venous thromboembolism, and bleeding in adults with nephrotic syndrome remain unclarified. METHODS: In this matched cohort study, we identified every adult with first-time recorded nephrotic syndrome from admissions, outpatient clinics, or emergency department visits in Denmark during 1995-2018. Each patient was matched by age and sex with 10 individuals from the general population. We estimated the 10-year cumulative risks of recorded arterial thromboembolism, venous thromboembolism, and bleeding accounting for the competing risk of death. Using Cox models, we computed crude and adjusted hazard ratios (HRs) of the outcomes in patients with nephrotic syndrome versus comparators. RESULTS: Among 3967 adults with first-time nephrotic syndrome, the 1-year risk of arterial thromboembolism was 4.2% (95% confidence interval [CI] 3.6-4.8), of venous thromboembolism was 2.8% (95% CI 2.3-3.3), and of bleeding was 5.2% (95% CI 4.5-5.9). The 10-year risk of arterial thromboembolism was 14.0% (95% CI 12.8-15.2), of venous thromboembolism 7.7% (95% CI 6.8-8.6), and of bleeding 17.0% (95% CI 15.7-18.3), with highest risks of ischemic stroke (8.1%), myocardial infarction (6.0%), and gastrointestinal bleeding (8.2%). During the first year, patients with nephrotic syndrome had increased rates of both arterial thromboembolism (adjusted HR [HRadj] = 3.11 [95% CI 2.60-3.73]), venous thromboembolism (HRadj = 7.11 [5.49-9.19]), and bleeding (HRadj = 4.02 [3.40-4.75]) compared with the general population comparators after adjusting for confounders. CONCLUSION: Adults with nephrotic syndrome have a high risk of arterial thromboembolism, venous thromboembolism, and bleeding compared with the general population. The mechanisms and consequences of this needs to be clarified.

Identifying Valid Algorithms for Number of Lines of Anti-Neoplastic Therapy in the Danish National Patient Registry Among Patients with Advanced Ovarian, Gastric, Renal Cell, Urothelial, and Non-Small Cell Lung Cancer Attending a Danish University Hospital.

PURPOSE: To develop algorithms to identify number of lines of anti-neoplastic therapy per patient based on the Danish National Patient Registry (DNPR) and identify which algorithm has the highest percentage agreement with a reference standard of documentation in medical records. PATIENTS AND METHODS: We included 179 patients diagnosed between January 1, 2012, and December 31, 2016, with stage II, III, or IV urothelial cell carcinoma or stage III or IV epithelial ovarian cancer, gastric adenocarcinoma, renal cell carcinoma, or non-small cell lung cancer (NSCLC). We developed two algorithms for number of lines of anti-neoplastic therapy based on dates and treatment codes (eg, "treatment with cisplatin" or "cytostatic treatment") in the DNPR. First, to denote a change in line of therapy the "Time-based algorithm" used the number of days between consecutive administrations. Second, the "Drug-based algorithm" used information on drug names if available or the number of days between consecutive administrations if no drug names were specified. We calculated the percentage agreement between the algorithms setting the number of allowed days between consecutive administrations from 28 to 50 and the reference standard - information on anti-neoplastic therapy drugs abstracted from medical records and subsequently coded according to lines of anti-neoplastic therapy. RESULTS: For the "Time-based algorithm", the highest percentage agreement with the reference standard was found when using <45 days between consecutive administrations (67.6%; 95% CI: 60.1-73.8%). However, the percentage agreement was higher for the "Drug-based algorithm" using <45 days between consecutive administrations for registrations where the drug name was unspecified (90.5%; 95% CI: 85.0-93.7%). CONCLUSION: The algorithm for number of lines of anti-neoplastic therapy that had the highest percentage agreement with the reference standard (medical records) incorporated both registration of specific drug names and <45 days between consecutive administrations if the drug name was unspecified in routinely recorded data from DNPR.

Association Between Atopic Dermatitis and Educational Attainment in Denmark.

IMPORTANCE: Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance. OBJECTIVE: To examine whether a childhood diagnosis of AD is associated with lower educational attainment. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021. EXPOSURES: Hospital-diagnosed AD. MAIN OUTCOMES AND MEASURES: Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age. RESULTS: The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]). CONCLUSIONS AND RELEVANCE: This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.

High-dose corticosteroid use and risk of hospitalization for infection in patients treated with immune checkpoint inhibitors--A nationwide register-based cohort study.

High-dose corticosteroids have been associated with increased risk of serious infection in patients with metastatic melanoma treated with immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4. This potential association needs to be examined further among patients with other cancer types and for other immune checkpoint inhibitors. We examined whether receipt of high-dose corticosteroids was associated with increased rates of hospitalization for infection among 981 Danish renal, urothelial, and lung cancer patients followed from first administration of programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors. Our cohort analysis was based on the information from national medical registries. During follow-up, 522 patients (53.2%) initiated treatment with high-dose corticosteroids and 317 patients (32.3%) experienced at least one hospitalization for infection. In analyses adjusted for age, sex, and previous use of chemotherapy/targeted therapy, initiation of high-dose systemic corticosteroids was associated with increased rate of hospitalization for infections (hazard ratio (HR) = 2.96, 95% confidence interval (CI) = 2.41-3.65) even in patients not receiving any chemotherapy/targeted therapy (HR = 3.66, 95% CI = 2.25-5.96). Our findings showed that high-dose corticosteroid initiation is associated with hospitalization for infection in patients treated with PD-1/PD-L1 immune checkpoint inhibitors. Clinicians and patients should be aware of this risk of infection when initiating treatment with high-dose corticosteroids.

Treatment and Survival in Advanced Non-Small Cell Lung Cancer, Urothelial, Ovarian, Gastric and Kidney Cancer: A Nationwide Comprehensive Evaluation.

PURPOSE: Few studies have described real-world treatment patterns and survival before the widespread use of immune checkpoint inhibitors (ICIs). We aimed to describe anti-cancer treatment including the use of programmed cell death-1 and ligand-1 (PD-1/PD-L1) ICIs and overall survival (OS) in advanced cancer patients as a benchmarking real-world standard before widespread use of ICIs. PATIENTS AND METHODS: Using nationwide Danish medical registries, we assembled cohorts of Danish patients with advanced non-small cell lung cancer (NSCLC) (n=12,283), urothelial carcinoma (n=2504), epithelial ovarian cancer (n=1466), gastric adenocarcinoma (n=1457), and renal cell carcinoma (RCC) (n=1261) diagnosed between 1/1/2013 and 31/12/2017. We describe anti-cancer treatment and OS using proportions, medians, and Kaplan-Meier methods. RESULTS: Between 9% (ovarian cancer) and 25% (gastric adenocarcinoma) of patients did not receive anti-cancer treatment. The remaining patients received surgery, radiation therapy, and/or medical therapy. Chemotherapy was the most frequent medical therapy in all cohorts except for RCC (tyrosine kinase inhibitors). PD-L1/PD-1 ICIs were used in 7-8% of the NSCLC and RCC cohorts-mainly as second or higher line treatments. OS was longest in patients starting treatment with surgery (eg 25.6 months [95%-confidence interval (CI)=21.9-29.4] for NSCLC and 21.4 months [95%-CI=19.8-23.5] for urothelial carcinoma) and shortest for radiation therapy (eg 3.9 months [95%-CI=3.6-4.2] for NSCLC and 12.6 months [95%-CI=9.2-17.5] for urothelial carcinoma). NSCLC patients starting with medical therapy had OS between these limits. Median OS for NSCLC patients starting treatment with PD-L1/PD-1 ICIs was 21.4 months (95%-CI=13.9-not estimable). CONCLUSION: Most patients with advanced NSCLC, urothelial carcinoma, epithelial ovarian cancer, gastric adenocarcinoma and RCC had poor OS in an era where only a minority received PD-L1/PD-1 ICIs. This information on treatment patterns and survival is important as a benchmarking real-world standard before widespread use of ICIs.

Metformin use and long-term risk of benign prostatic hyperplasia: a population-based cohort study.

OBJECTIVE: To assess whether metformin use affects risk of benign prostatic hyperplasia (BPH) by comparing the risk of BPH in men with type 2 diabetes who initiated first-line treatment with either metformin or sulfonylurea monotherapy between 2000 or 2006 in Northern Denmark. In this period, sulfonylurea and metformin were both frequently used as first-line glucose-lowering drug (GLD) treatment. DESIGN: A population-based cohort study. SETTING: Northern Denmark. PARTICIPANTS: All men who filled at least two prescriptions for metformin or for sulfonylurea, respectively, during their first 6 months of GLD treatment. Follow-up started 6 months after treatment start. PRIMARY OUTCOME MEASURES: Rates of subsequent BPH, identified based on community prescriptions for BPH-related treatment or hospital BPH diagnoses, and rates of transurethral resection of the prostate (TURP). Rates in metformin and sulfonylurea users were compared overall and stratified by 6-month haemoglobin A1c (HbA1c) using Cox regression and an intention-to-treat (ITT) approach and an as-treated analysis. RESULTS: During follow-up, less than five persons were lost to follow-up due to emigration. In 3953 metformin initiators with a median follow-up of 10 years, the 10-year cumulative BPH incidence was 25.7% (95% CI 24.2 to 27.1). Compared with 5958 sulfonylurea users (median follow-up 8 years, 10-year cumulative incidence 27.4% (95% CI 26.2 to 28.6)), the crude HR for BPH was 0.83 (95% CI 0.77 to 0.89) and adjusted HR in the ITT analyses was 0.97 (95% CI 0.88 to 1.06). For TURP, the adjusted HR was 0.96 (95% CI 0.63 to 1.46). In the as-treated analysis, adjusted HR for BPH was 0.91 (95% CI 0.81 to 1.02). CONCLUSIONS: Compared with sulfonylurea, metformin did not substantially reduce the incidence of BPH in men with diabetes.

Platelet Count within the Normal Range at Hospital Admission is Associated with Mortality in Patients with Community-Acquired Pneumonia.

BACKGROUND: Apart from their hemostatic role, platelets are immune cells that play a role in fighting infections. The presence of thrombocytopenia and thrombocytosis at hospital admission are predictors of mortality in community-acquired pneumonia patients. We hypothesized that variations in platelet counts within the normal range also may be associated with mortality in these patients. METHODS: The study included all adults in the North and Central Denmark Regions with a first acute hospital admission for community-acquired pneumonia during 2006-2012. We assessed the association between the first platelet count within ± 24 hours of admission (within the normal range of 150 to 400 x 109/L) and 30-day mortality using Cox models. Analyses were adjusted for age, sex, Charlson Comorbidity Index score, hemoglobin level, leukocyte count, and creatinine level at admission. RESULTS: Among the 12,905 study patients, 30-day mortality was 12.4%. The mean platelet count upon admission was 250 × 109/L. Compared with the 250-275 × 109/L category, platelet counts of 151-175 were associated with a lower 30-day mortality (adjusted hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.63-0.99), while higher platelet counts were associated with a higher 30-day mortality (351-375 × 109/L, aHR: 1.34, 95% CI: 1.07-1.68; 376-400× 109/L, aHR: 1.21, 95% CI: 0.94-1.56). CONCLUSION: Platelet counts, even within the normal range, are associated with mortality in adult patients hospitalized for community-acquired pneumonia.

Long-term mortality in young and middle-aged adults hospitalised with chronic disease: a Danish cohort study.

OBJECTIVES: To examine the long-term outcomes for patients hospitalised with chronic diseases at age 30, 40 or 50 years. DESIGN: Nationwide, population-based cohort study. SETTING: All Danish hospitals, 1979-1989, with follow-up through 2014. PARTICIPANTS: Patients hospitalised during the study period with one, two or three or more chronic diseases and age-matched and sex-matched persons from the general population without chronic disease leading to hospitalisation: age-30 group: 13 857 patients and 69 285 comparators; age-40 group: 24 129 patients and 120 645 comparators; and age-50 group, 37 807 patients and 189 035 comparators. MAIN OUTCOME MEASURES: Twenty-five-year mortality risks based on Kaplan-Meier estimates, years-of-life-lost (YLLs) and mortality rate ratios based on Cox regression analysis. YLLs were computed for each morbidity level, as well as in strata of income, employment, education and psychiatric conditions. RESULTS: Twenty-five-year mortality risks and YLLs increased steadily with increasing number of morbidities leading to hospitalisation and age, but the risk difference with general population comparators remained approximately constant across age cohorts. In the age-30 cohort, the risk differences for patients compared with comparators were 35.0% (95% CI 32.5 to 37.5) with two diseases and 62.5% (54.3% to 70.3%) with three or more diseases. In the age-50 cohort, these differences were, respectively, 48.4% (47.4 to 49.3) and 61.7% (60.1% to 63.0%). Increasing morbidity burden augmented YLLs resulting from low income, unemployment, low education level and psychiatric conditions. In the age-30 cohort, YYLs attributable to low income were 2.4 for patients with one disease, 6.2 for patients with two diseases and 11.5 for patients with three or more diseases. CONCLUSIONS: Among patients with multiple chronic diseases, the risk of death increases steadily with the number of chronic diseases and with age. Multimorbidity augments the already increased mortality among patients with low socioeconomic status.

Association Between Atopic Eczema and Cancer in England and Denmark.

Importance: Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk. Objective: To investigate whether atopic eczema is associated with cancer. Design, Setting, and Participants: Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema. Exposure: Atopic eczema. Main Outcomes and Measures: Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema. Results: In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide. Conclusions and Relevance: The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.

Risk of thromboembolic and bleeding outcomes following hematological cancers: A Danish population-based cohort study.

BACKGROUND: Therapeutic advances have improved survival after hematological cancers. In turn, patients may be at increased risk of thromboembolic and bleeding events. OBJECTIVES: To examine the risks of myocardial infarction (MI), ischemic stroke, venous thromboembolism (VTE), and bleeding requiring hospital contact in patients with hematological cancers. METHODS: We conducted a Danish population-based cohort study (2000-2013). We identified all adult hematological cancer patients and sampled a general population comparison cohort in a 1:5 ratio matched by age, sex, previous thromboembolic events, bleeding, and solid cancer. Ten-year absolute risks of thromboembolism and bleeding were calculated and hazard ratios (HRs) were computed, controlling for matching factors. RESULTS: Among 32 141 hematological cancer patients, the 10-year absolute risk of any thromboembolic or bleeding complication following hematological cancer was 19%: 3.3% for MI, 3.5% for ischemic stroke, 5.2% for VTE, and 8.5% for bleeding. Except among patients with myeloid leukemia, acute lymphoid leukemia, or myelodysplastic syndrome, the risk of thromboembolic events surpassed that of bleeding. The hematological cancer cohort overall was at increased risk for MI [HR = 1.36, 95% confidence interval (CI): 1.25-1.49], ischemic stroke (HR = 1.22, 95% CI: 1.12-1.33), VTE (HR = 3.37, 95% CI: 3.13-3.64), and bleeding (HR = 2.39, 95% CI: 2.26-2.53) compared with the general population. CONCLUSIONS: Approximately 2 of 10 hematological cancer patients experienced MI, ischemic stroke, VTE, or bleeding requiring hospital contact within 10 years. The hematological cancer cohort had higher hazards of MI, ischemic stroke, VTE, and bleeding requiring hospital contact than a general population comparison cohort.

Risk of bleeding and arterial cardiovascular events in patients with splanchnic vein thrombosis in Denmark: a population-based cohort study.

BACKGROUND: Little is known about adverse events following splanchnic vein thrombosis. Venous thromboembolism has been associated with increased risks of bleeding and arterial cardiovascular events. To learn more about the clinical course of splanchnic vein thrombosis, we examined the risks of bleeding and arterial cardiovascular events in patients with the disease, and compared them with the risks in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) and individuals from the general population. METHODS: In this population-based cohort study, we used data for all patients with a diagnosis of splanchnic vein thrombosis recorded in the Danish National Patient Registry (DNPR) between Jan 1, 1994, and Nov 30, 2013 (cumulative source population 7 310 450 individuals). We created two comparison cohorts using data from the DNPR and the Civil Registration System for the same period: one of patients with DVT or PE and another of individuals from the general population. Comparison cohorts (ten comparators per patient with splanchnic vein thrombosis) were matched on sex, age, and calendar year of diagnosis. We calculated absolute risks and used proportional hazard regression to calculate adjusted hazard ratios (HRs) for the primary outcomes of bleeding and arterial cardiovascular events after splanchnic vein thrombosis diagnosis (or the index date for comparison cohorts). FINDINGS: 1915 patients with splanchnic vein thrombosis, 18 373 patients with DVT or PE, and 19 150 individuals from the general population were included in the study. Patients with splanchnic vein thrombosis were followed up for a median of 1 year (IQR 0·1-3·9). These patients had a high risk of bleeding in the 30 days after diagnosis, both in absolute terms (4·3% [95% CI 3·5-5·3]) and in adjusted models (HR 9·64 [95% CI 6·46-14·40] vs DVT or PE; 39·79 [19·44-81·46] vs general population). Bleeding risk was still significantly increased in patients with splanchnic vein thrombosis up to 1 year after diagnosis (HR 3·01 [95% CI 2·28-3·97] vs DVT or PE; 6·83 [4·83-9·65] vs general population), and remained elevated for up to 10 years compared with patients with DVT or PE (1·93 [1·12-3·34]) and for up to 19 years compared with the general population (5·90 [2·22-15·64]). The risk of arterial cardiovascular events in patients with splanchnic vein thrombosis was high in the year after diagnosis (absolute risk 3·3% [95% CI 2·6-4·2] up to 30 days; 7·0% [5·8-8·4] up to 31-365 days), and in adjusted models was significantly higher than in patients with DVT or PE (HR 7·05 [95% CI 4·74-10·48] up to 30 days; 2·10 [1·62-2·72] up to 31-365 days) and individuals from the general population (15·75 [9·26-26·79] and 3·17 [2·34-4·27], respectively). However, this risk did not remain significantly elevated above that of patients with DVT or PE after 1 year or the general population after 5 years. INTERPRETATION: Patients with splanchnic vein thrombosis are at increased risk of adverse outcomes, particularly bleeding but also arterial cardiovascular events, for years after diagnosis compared with patients with DVT or PE and the general population. Physicians should be cognisant of these risks in patients with splanchnic vein thrombosis. FUNDING: The Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo Nordisk Foundation.

Survival after splanchnic vein thrombosis: A 20-year nationwide cohort study.

INTRODUCTION: Splanchnic vein thrombosis (SVT) is a rare condition with a poorly understood prognosis. MATERIALS AND METHODS: We conducted a population-based cohort study (1994-2013), using data from Danish nationwide medical registries, to examine the short- and long-term prognosis of SVT. We identified 1915 incident cases of SVT and a matched comparison cohort of 18,267 persons without SVT (matched by cancer, cirrhosis, pancreatitis, alcohol-related disease, atrial fibrillation/flutter, venous thromboembolism, heart failure, and inflammatory bowel disease). We used the Kaplan-Meier method to calculate absolute risk of death. Using stratified Cox regression, we computed mortality rate ratios (MRRs) with 95% confidence intervals (CIs), comparing SVT patients with the comparison cohort. RESULTS: We identified 1,500 (78%) patients with portal vein thrombosis, 204 (11%) with hepatic vein thrombosis, and 211 (11%) with mesenteric vein thrombosis. The mortality risks were markedly higher for SVT patients than for the comparison cohort during the first 5years of follow-up (30-day risk: 20.6% vs. 0.7%; 31-364-day risk: 21.7% vs. 4.7%; and 1-5-year risk: 25.4% vs. 17.7%). The corresponding MRRs were 40.7 (95% CI: 32.4-51.1), 7.4 (95% CI: 6.4-8.6), and 2.4 (95% CI: 2.1-2.8), respectively. The 30-day mortality was higher after mesenteric vein thrombosis than portal and hepatic vein thrombosis, whereas portal vein thrombosis had a stronger impact on mortality after 30days than hepatic and mesenteric vein thrombosis. CONCLUSIONS: Splanchnic vein thrombosis has a poor short- and long-term prognosis that varies according to subtype of thrombosis. Reasons for the increased mortality in patients with SVT need further clarification.