Studies on long-term mortality after venous thromboembolism (VTE) are sparse.
Using Danish medical databases, we conducted a 30-year nationwide population-based cohort study of 128 223 patients with first-time VTE (1980-2011) and a comparison cohort of 640 760 people from the general population (without VTE) randomly matched by sex, year of birth, and calendar period. The mortality risks for patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (3.0% and 31% versus 0.4%). Using Cox regression, we assessed mortality rate ratios (MRRs) with 95% confidence intervals (CIs). The overall 30-year MRR was 1.55 (95% CI, 1.53-1.57) for DVT and 2.77 (95% CI, 2.74-2.81) for PE. The 30-day MRR was 5.38 (95% CI, 5.00-5.80) for DVT and 80.87 (95% CI, 76.02-86.02) for PE. Over time, the 30-day MRR was consistently 5- to 6-fold increased for DVT, whereas it improved for PE from 138 (95% CI, 125-153) in 1980 to 1989 to 36.08 (95% CI, 32.65-39.87) in 2000 to 2011. The 1- to 10-year and 11- to 30-year MRRs remained 25% to 40% increased after both DVT and PE but were 3- to 5-fold increased after DVT and 6- to 11-fold increased after PE when VTE was considered the immediate cause of death.
Patients with VTE are at increased risk of dying, especially within the first year after diagnosis, but also during the entire 30 years of follow-up, with VTE as an important cause of death. Although 30-day mortality after DVT remained fairly constant over the last 3 decades, it improved markedly for PE.
Giving birth to a child with a major birth defect is a serious life event for a woman, yet little is known about the long-term health consequences for the mother.
To assess whether birth of an infant born with a major congenital anomaly was associated with higher maternal risk of mortality.
This population-based cohort study (n?=?455?250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly (41?508) between 1979 and 2010, with follow-up until December 31, 2014. A comparison cohort (413?742) was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity, and year of infant's birth.
Live birth of an infant with a major congenital anomaly as defined by the European Surveillance of Congenital Anomalies classification system.
Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality. Hazard ratios (HRs) were adjusted for marital status, immigration status, income quartile (since 1980), educational level (since 1981), diabetes mellitus, modified Charlson comorbidity index score, hypertension, depression, history of alcohol-related disease, previous spontaneous abortion, pregnancy complications, smoking (since 1991), and body mass index (since 2004).
Mothers in both groups were a mean (SD) age of 28.9 (5.1) years at delivery. After a median (IQR) follow-up of 21 (12-28) years, there were 1275 deaths (1.60 per 1000 person-years) among 41?508 mothers of a child with a major congenital anomaly vs 10?112 deaths (1.27 per 1000 person-years) among 413?742 mothers in the comparison cohort, corresponding to an absolute mortality rate difference of 0.33 per 1000 person-years (95% CI, 0.24-0.42), an unadjusted HR of 1.27 (95% CI, 1.20-1.35), and an adjusted HR of 1.22 (95% CI, 1.15-1.29). Mothers with affected infants were more likely to die of cardiovascular disease (rate difference, 0.05 per 1000 person-years [95% CI, 0.02-0.08]; adjusted HR, 1.26 [95% CI, 1.04-1.53]), respiratory disease (rate difference, 0.02 per 1000 person-years [95% CI, 0.00-0.04]; adjusted HR, 1.45 [95% CI, 1.01-2.08]), and other natural causes (rate difference, 0.11 per 1000 person-years [95% CI, 0.07-0.15]; adjusted HR, 1.50 [95% CI, 1.27-1.76]).
In Denmark, having a child with a major congenital anomaly was associated with a small but statistically significantly increased mortality risk in the mother compared with women without an affected child. However, the clinical importance of this association is uncertain.
The impact of cancer and other comorbidity on the risk of venous thromboembolism (VTE) after stroke is poorly understood.
We used Danish population-based national databases to conduct a cohort study encompassing 201,025 patients diagnosed with a first-time ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage or unspecified stroke between 1995 and 2012. As a comparison cohort, 983,222 members of the general population were matched to the stroke patients by date of diagnosis, year of birth, sex, and specific comorbidities, using conditions in the Charlson Comorbidity Index and other VTE risk factors. We computed VTE cumulative risks, rates, and rate ratios. We examined the interaction with comorbidity, defined as the excess VTE rates not explained by stroke and comorbidity alone, for up to five years following stroke.
Five-year VTE risks were 2.1% and 1.9% in the stroke and comparison cohorts, respectively. Three-month VTE rates peaked at a 5-fold increase (95% confidence interval [CI]: 4.4; 5.2) in stroke patients and remained 13% to 43% increased relative to the general population during subsequent follow-up. During the first three months after stroke, 15% to 33% of the VTE rates were attributable to the interaction between stroke and moderate (2-3) to high (=4) comorbidity based on Charlson Comorbidity Index scores. Non-metastatic solid tumors and metastatic disease accounted for most observed interaction with stroke, representing 41% and 56% of attributable three-month VTE rates, respectively. No such interaction between comorbidity and stroke was observed during subsequent follow-up.
Comorbidity, particularly cancer, increased the risk of VTE within three months following stroke.
Population-based studies of site-specific cancer risk in patients with inflammatory bowel disease (IBD) according to IBD phenotype and treatment are lacking. We studied cancer risk in a well-characterized population-based IBD cohort from North Jutland County, Denmark.
A total of 1,515 patients were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD) during 1978-2002. Patients were followed until 31 December 2010 for occurrence of incident cancer, identified in the Danish Cancer Registry. Observed numbers of cancer were compared with expected numbers (based on age- and sex-specific background rates) and presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs).
Patients with UC were not at increased risk of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55% increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young age, colonic disease, smoking, and thiopurine exposure. Patients were at increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis, smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)).
Patients with CD, but not UC, have an overall excess risk of cancer. Clinical characteristics of IBD patients at excess risk differ by cancer subtype.
Patients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We conducted a population-based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980-2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3·01% (95% confidence interval (CI): 2·20-4·10), 4·74% (95%CI: 4·06-5·52) and 4·64% (95%CI: 3·29-6·53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1·19-fold (95% CI: 0·94-1·51) for ET patients, 1·82-fold (95% CI: 1·62-2·04) for PV patients, and 2·67-fold (95% CI: 1·97-3·62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population.
Venous thromboembolism (VTE) is a major source of morbidity and mortality in cancer patients. Incident colorectal cancer (CRC) and comorbidity both predict VTE, but potential synergy between these factors has not been explored.
Danish nationwide cohort study of CRC cases diagnosed in 1995-2010 and a matched general population reference cohort of subjects without CRC who matched cases on age, sex, and comorbidities. We calculated the Charlson Comorbidity Index using diagnoses recorded in the Danish National Patient Registry. We calculated standardised incidence rates (SIRs) and interaction contrasts (IC) to measure additive interaction between comorbidity and CRC status with respect to 5-year VTE incidence.
Among 56?189 CRC patients, 1372 VTE cases were diagnosed over 145?211 person-years (SIR=9.5 cases per 1000 person-years). Among 271?670 reference subjects, 2867 VTE cases were diagnosed over 1?068 ?860 person-years (SIR=2.8 cases per 1000 person-years). CRC and comorbidity were positively and independently associated with VTE, but there was no evidence for biological interaction between these factors (e.g., comparing the 'severe comorbidity' stratum with the 'no comorbidity' stratum, IC=0.8, 95% CI: -3.3, 4.8).
There is neither a deficit nor a surplus of VTE cases among patients with both comorbidity and CRC, compared with rates expected from these risk factors in isolation.
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In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only.
From January 2002 to June 2009 all patients treated with PPCI were identified from the Western Denmark Heart Registry. We examined mortality according to timing of multivessel PCI: acute procedure, staged procedure during the index hospitalisation, or staged procedure performed within 60 days. The hazard ratio (HR) for death was estimated using a time-dependent Cox regression model, with time of PCI for the non-culprit lesion as the time-dependent variable. The study cohort consisted of 5,944 patients, of whom 4,770 (80%) had single-vessel disease and 1,174 (20%) had multivessel PCI within 60 days. Among 354 (30.2%) patients with acute multivessel PCI, 194 (16.5%) patients with multivessel PCI during the index hospitalisation, and 626 (53.3%) patients with multivessel PCI within 60 days after the index hospitalisation, the adjusted HRs for one-year mortality were 1.53 (95% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease.
Acute multivessel PCI in patients with STEMI was associated with increased mortality.
Cushing's syndrome (CS) affects all age groups, but epidemiologic data in young patients are very limited. We therefore examined the incidence, prevalence and hospital morbidity of CS in children and adolescents.
In a nationwide cohort study, we included all Danish citizens aged 0-20 years from 1977 to 2012. Data were obtained from the Danish National Patient Registry using the International Classification of Diseases (ICD) codes and the Danish Civil Registration System. The diagnosis and treatment were validated by means of individual patient charts. Incidence rate of CS patients aged 0-20 years at diagnosis were computed (standardized to the age and sex distribution of the Danish population). The patients were followed for a maximum of 36 years. Standardized incidence ratios (SIRs) of different hospital-recorded outcomes based on the ICD codes in patients with CS compared to the general population were assessed.
We identified a total of 40 pediatric patients with CS, yielding an annual incidence of 0.89 cases/10(6) population (95% confidence interval (CI)?=?0.63-1.16). The median age at the time of diagnosis was 13.8 years (interquartile range: 10.5-18.2 years), 58% were female and 70% had adrenocorticotropic hormone-producing pituitary adenomas. During follow-up, CS patients (excluding three malignant cases) were at increased risk of being diagnosed with infections (SIR: 3.24, 95% CI: 1.05-7.54) and infertility (SIR: 4.56, 95% CI: 1.48-10.63). The three patients with an adrenocortical carcinoma died shortly after diagnosis, but mortality was not increased in the remaining patients.
CS is rare in the pediatric population. The risk of morbidity related to infections and infertility is elevated and merits further attention.
Diverticular disease and cardiovascular disease share several risk factors. Inflammation associated with diverticular disease could predispose to cardiovascular disease. We assessed the association between a diagnosis of diverticular disease and subsequent arterial and venous thromboembolic events, adjusting for related comorbidities to explore a possible causal relationship.
We identified 77,065 incident cases of diverticular disease from 1980-2011 from Danish nationwide medical registries; these were matched for age and sex with 302,572 population comparison cohort members. Individuals with a history of cardiovascular disease were excluded. We used Cox proportional hazards regression to compute incidence rate ratios, comparing the incidence of acute myocardial infarction, stroke, venous thromboembolism, and subarachnoid hemorrhage in patients with diverticular disease with those of the population cohort members, adjusting for age, sex, obesity, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, connective tissue disease, renal disease, and treatments and medications.
The adjusted incidence rate ratios for patients with diverticular disease, compared with population cohort members, were 1.11 (95% confidence interval [CI], 1.07-1.14) for acute myocardial infarction, 1.11 (95% CI, 1.08-1.15) for overall stroke, 1.36 (95% CI, 1.30-1.43) for overall venous thromboembolism, and 1.27 (95% CI, 1.09-1.48) for subarachnoid hemorrhage. The relative risk of each event remained increased after we adjusted for changes in aspirin use or for endoscopy or colorectal surgery after the diagnosis of diverticular disease. These findings also held after excluding the first year of follow-up and limiting the analysis to patients with diverticulitis.
On the basis of an analysis of Danish medical registries, a diagnosis of diverticular disease is associated with a modest increase in risk of arterial and venous thromboembolic events after adjustment for related disorders.