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Søren Hauge Okholm,1 Dávid Nagy,1 Dóra Körmendiné Farkas,1 Cecilia Hvitfeldt Fuglsang,1 Frederikke Schønfeldt Troelsen,1 Victor W Henderson,1,2 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USACorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 15, Email hts@clin.au.dkIntroduction: 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.Keywords: cancer, cohort study, epidemiology, non-traumatic subdural hematoma, population-based

Purpose: We examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all-cause mortality compared with use of other long-acting beta2-agonists (LABAs). Channelling bias was also explored. Methods: This Danish population-based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias. Results: The IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n = 14 239) compared to users of other LABAs (n = 51 167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44–1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97–1.64) among LABA-naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03–1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19–1.48) after applying overlap-weights analysis. Conclusions: Olodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all-cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

Background Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. Objectives To examine the cancer risk in patients with kidney disease following a VTE. Methods We conducted a nationwide population-based cohort study in Denmark (1996–2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. Results We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6–5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3–5.8), with a SIR of 2.9 (95% CI: 2.5–3.4) when compared with the general population, and 2.0 (95% CI: 1.8–2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3–1.6) when compared with the general population, and 1.1 (95% CI: 0.9–1.2) compared with VTE patients without kidney disease. Conclusions Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

Introduction: It is unclear whether Guillain-Barré syndrome (GBS) can be a marker of a paraneoplastic syndrome. We examined whether GBS is associated with cancer and whether the prognosis of GBS patients with cancer differs from that of other cancer patients.Materials and Methods: We conducted a population-based cohort study of patients diagnosed with GBS between 1978 and 2017 using Danish registry-data. Main outcome measures were cancer incidence and mortality after cancer diagnosis. We calculated absolute risks of a cancer diagnosis, treating death as competing risk, and standardized incidence ratios (SIRs) as measures of relative risk. We matched each GBS cancer patient with up to 10 cancer patients without a GBS diagnosis and examined the six-month survival after cancer diagnosis using Cox regression analysis.Results: We identified 7897 patients (58% male, median age 57 years) with GBS. During a median follow-up of 9.5 years, the one-year risk of cancer was 2.7% (95% confidence interval (CI), 2.4-3.1). The SIR was increased throughout follow-up, but most noticeably during the first year after diagnosis (SIR: 3.35, 2.92-3.83). SIRs were particularly elevated for hematologic cancers (SIR: 8.67, 6.49-11.34), smoking-related cancers (SIR: 3.57, 2.81-4.47), and cancers of neurological origin (SIR: 8.60, 5.01-13.77). Lung cancer was the main contributor to the overall excess risk, which persisted after 36 months of follow-up (SIR: 1.17, 1.09-1.25). The mortality rate ratio comparing patients diagnosed with any cancer within one year of their GBS diagnosis and matched GBS-free cancer cohort members was 1.56 (95% CI, 1.27-1.90).Conclusion: GBS patients had a three-fold increased risk of cancer diagnosis in the first year of follow-up. The absolute cancer risk was almost 3.0%. A GBS diagnosis was an adverse prognostic marker for survival following cancer diagnosis. Clinicians should consider occult cancer in patients hospitalized with GBS.

Background Some neurogenerative diseases have been linked to a reduced risk of cancer, but the association between motor neuron disease and cancer risk is not well understood. We hypothesized that cancer risk would be lower among those with motor neuron disease and its most common subtype, amyotrophic lateral sclerosis. Methods We conducted a population-based cohort study of motor neuron disease and cancer risk using routinely collected data from population-based registries in Denmark. We examined cancer incidence among patients diagnosed with motor neuron disease between January 1980 and December 2013 followed through 2013. Using Danish national cancer rates for the study period, we computed standardized incidence ratios as a measure of relative risks. Results In the cohort of 5053 patients with a motor neuron disease, the overall standardized incidence ratio of any cancer was 1.17 (95% confidence interval [CI], 1.03-1.31); the corresponding standardized incidence ratio for amyotrophic lateral sclerosis was 1.24 (95% CI, 0.96-1.57). The standardized incidence ratios of any cancer in the cohort with motor neuron disease was 1.52 (95% CI, 1.22-1.87) for 5 years of follow-up. Beyond one year of follow-up, patients in the motor neuron disease had elevated standardized incidence ratios for lymphoid leukemia, non-Hodgkin lymphoma, and basal cell skin cancer. Conclusion Findings fail to support the hypothesis that motor neuron disease or amyotrophic lateral sclerosis is associated with reduced cancer incidence. An elevated risk of cancer during the first year of follow-up may be attributable to heightened surveillance.

Sigrid Bjerge Gribsholt,1,2 Dóra Körmendiné Farkas,3 Reimar Wernich Thomsen,3 Bjørn Richelsen,1,2 Henrik Toft Sørensen3 1Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, DenmarkCorrespondence: Sigrid Bjerge Gribsholt, Tel +4561651148, Email sigrid.bjerge.gribsholt@clin.au.dkPurpose: Data on long-term mortality among patients with hospital-diagnosed overweight/obesity are limited. Thus, we aim to examine 40-year mortality among patients with hospital-diagnosed overweight/obesity, including cause-specific deaths, secular time trends, and potential effect modification by age, comorbidity, and socioeconomic factors.Patients and Methods: From national registries, we identified all Danes with a first hospital-based overweight/obesity diagnosis (N=331,185), 1979– 2018, and constructed an age- and gender-matched general population comparison cohort (N=1,655,925). We computed mortality rates (MRs) per 1000 person-years and adjusted mortality rate ratios (aMRRs) with 95% confidence intervals (CIs), using Cox regression with adjustment for comorbidities and educational level. We performed stratified analyses on age, comorbidities, and socioeconomic factors.Results: The overall aMRR was 1.70 (95% CI: 1.68– 1.72) for patients with overweight/obesity, mainly due to diabetes and other endocrine diseases (aMRR=2.68 [95% CI: 2.57– 2.81]), cardiovascular (aMRR=1.95 [95% CI: 1.91– 1.98]), and respiratory diseases (aMRR=1.83 [95% CI: 1.77– 1.89]). The 1– 10-year aMRR decreased from 2.06 (95% CI: 2.01– 2.11) in 1979– 1989 to 1.29 (95% CI: 1.26– 1.32) in 2000– 2009. We found effect modification by age: age 18 to < 30 years: aMRR=2.44 (95% CI: 2.24– 2.66) vs age ≥ 70 years: 1.35 (95% CI: 1.33– 1.37); comorbidities: baseline comorbidities: aMRR=1.13 (95% CI: 1.10– 1.15) vs no comorbidities: aMRR=1.83 (95% CI: 1.80– 1.85); and educational level: high educational level: aMRR=1.81 (95% CI: 1.74– 1.88) vs low educational level: aMRR=1.70 (95% CI: 1.67– 1.72).Conclusion: Patients with overweight/obesity had a substantially increased long-term mortality, mainly due to diabetes, cardiovascular, and respiratory diseases. The excess mortality decreased during recent decades. Age, comorbidities, and socioeconomic factors modified the association.Keywords: cohort study, epidemiology, mortality, multi-morbidity, obesity, overweight, socio-economy

Henrik Toft Sørensen,1 Nils Skajaa,1 Frederikus Albertus Klok,2 Kristina Laugesen,1 Dóra Körmendiné Farkas1 1Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, DK-8200, Denmark; 2Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the NetherlandsCorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Allé 43-45, Aarhus N, DK-8200, Denmark, Email hts@clin.au.dkBackground: Strong evidence indicates that venous thromboembolism is a presenting symptom of cancer. Cancer is a known cause of pulmonary hypertension; however, it remains unknown whether pulmonary hypertension is a marker of occult cancer. We examined the association between a pulmonary hypertension diagnosis and cancer risk in a cohort study using population-based data from the Danish health system.Patients and Methods: Using Danish nationwide registries, we identified 6335 patients with a pulmonary hypertension diagnosis and without a previous cancer diagnosis between 1995 and 2017. We computed the age-, sex-, and calendar year-standardized incidence ratio (SIR) as the ratio of observed to expected number of cancers using national incidence rates as the reference. We performed a subgroup analysis among patients with chronic thromboembolic pulmonary hypertension in the period in which a specific ICD-10 code was available (2006– 2017).Results: We identified 212 cancers within the first year of follow-up and 796 cancers thereafter. The one-year risk of cancer was 3.3% and the one-year SIR was 1.96 (95% confidence interval [CI]: 1.70– 2.23). In the second and subsequent years, the SIR remained elevated (SIR: 1.15 [95% CI: 1.08– 1.24]). In patients with chronic thromboembolic pulmonary hypertension, the one-year SIR was 1.41 (95% CI: 0.82– 2.25).Conclusion: Cancer risk was clearly higher in patients with pulmonary hypertension compared with the general population. The association was particularly strong in the first year of follow-up, but remained elevated thereafter. However, absolute risks were low, limiting the clinical relevance of pursuing early cancer detection in these patients.Keywords: pulmonary hypertension, chronic thromboembolic pulmonary hypertension, venous thrombosis, pulmonary embolism, cancer, cohort

OBJECTIVE: The purpose of this study was to examine overall and site-specific cancer risk among individuals diagnosed with migraine compared with the general population.BACKGROUND: Current evidence regarding migraine and risk of cancer is sparse and inconclusive.METHODS: We conducted a nationwide population-based cohort study with data collected routinely and prospectively from Danish population-based registries from 1995 to 2017. We computed the age- and sex-standardized incidence ratio (SIR) as the ratio of observed to expected cancers among patients diagnosed with migraine in the study population overall, and by encounter type of first diagnosis (inpatient, outpatient specialty clinic, and emergency department). Site-specific cancers were grouped according to etiology.RESULTS: We identified 72,826 patients with a first-time hospital migraine diagnosis. There were 3090 observed overall cancer cases among individuals diagnosed with migraine as compared with 3108 expected cases (SIR 0.99, 95% confidence interval [CI]: 0.96-1.03). The cumulative incidence of all cancers combined from 1995 to 2017 among those with a first-time migraine diagnosis was 9.47% (95% CI: 9.08-9.87). The SIRs for most cancers were consistent with absence of an association: 1.00 (95% CI: 0.94-1.06) for hormone-related cancers, 0.96 (95% CI: 0.88-1.03) for smoking-related cancers, 1.10 (95% CI: 0.98-1.24) for hematologic cancers, and 0.95 (95% CI: 0.85-1.06) for immune-related cancers. Exceptions were SIRs for gastrointestinal cancers (0.78, 95% CI: 0.70-0.87) and for cancers of neurological origin (1.57, 95% CI: 1.40-1.76).CONCLUSIONS: For most cancer groups, our results did not support an association with migraine. The exceptions were an increased risk for cancers of neurological origin and a decreased risk for gastrointestinal cancers. These findings may reflect a true difference in risk among individuals with migraine, or more plausibly they reflect other forces, such as differences in medication use, detection bias and reverse causation, or shared risk factors.

ObjectiveTo examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention.DesignNationwide population based cohort study.SettingAll hospitals in Denmark.Participants75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017.Main outcome measuresAbsolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population.ResultsThe absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years.ConclusionsAcute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause.

Purpose Venous thromboembolism may be a harbinger of cancer. Patients with diverticular disease are suggested to have an increased risk of developing venous thromboembolism compared with the general population, but it remains unclear whether venous thromboembolism is also a marker of occult cancer in these patients. We investigated the risk of cancer after venous thromboembolism among patients with diverticular disease. Patients and Methods We used Danish health registries to conduct a nationwide, population-based cohort study during 1996–2017. We identified all venous thromboembolism patients with a diagnosis of diverticular disease and calculated absolute risks of cancer and standardized incidence ratios (SIRs) by comparing observed and expected cancer incidence based on national cancer incidence in the Danish population. Results We followed 3406 patients with venous thromboembolism and diverticular disease for a median of 3.0 years (interquartile range: 1.0–6.0). During the first year of follow-up, we observed 212 cancer cases. The corresponding one-year risk of cancer was 6.2% (95% confidence interval [CI]: 5.5–7.1) with a SIR of 2.9 (95% CI: 2.5–3.3). The SIRs were particularly elevated for cancers of the stomach, pancreas, ovary, and kidney. During the second and subsequent years of follow-up, 337 cancers were diagnosed with a SIR of 1.1 (95% CI: 1.0–1.3). Conclusion Venous thromboembolism is a harbinger of occult cancer in patients with diverticular disease., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/F_5MPyAQSAk

BackgroundAdults with congenital heart disease (CHD) are at increased risk for major adverse cardiovascular events (MACE), including stroke, myocardial infarctions, and heart failure. Following survival of MACE, an important metric is re-entry to the workforce. This study sought to characterize the differences in return-to-work (RTW) characteristics between MACE survivors with CHD and those in the general population.MethodsLinking Danish health and administrative registries, a cohort of adults with CHD who survived a MACE between the years of 1992–2017 were matched 10:1 by age at MACE, year of MACE, and sex to MACE survivors without CHD. Logistic regression assessed working status relative risk at three-, six-, and 12- months after the MACE event. Cox regression hazard ratio characterized time to RTW and maintained RTW.ResultsDuring the study period, 538 CHD patients survived MACE. These patients were matched to 4930 MACE survivors without CHD. The adjusted odds ratios of having returned to work were 0.91 (95% confidence interval (CI): 0.73–1.14) of employment at three months, 0.77 (95% CI: 0.61–0.96) at six months, and 0.76 (95% CI: 0.61–0.96) at 12 months. Of those who required governmental disability payments after MACE and admission for longer than one day, the adjusted hazard ratio of maintained RTW was 0.83 (95% CI: 0.69–0.99) for CHD patients compared to the general population.ConclusionsPatients with CHD who survive a MACE have evidence of impaired RTW compared to those without CHD. Further research is needed to understand and augment functional recovery in this complex population.

Background We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population. Methods Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994–2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI). Results Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1–20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4–3.0) for lung cancer, 2.0 (95% CI: 1.8–2.2) for colorectal cancer, 1.7 (95% CI: 1.5–1.9) for prostate cancer and 10.0 (95% CI: 8.6–11.4) for brain cancer. Conclusions Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted.

BackgroundProspective population-based studies of psychiatric comorbidity following trauma and severe stress exposure in children are limited.AimsTo examine incident psychiatric comorbidity following stress disorder diagnoses in Danish school-aged children using Danish national healthcare system registries.MethodChildren (6–15 years of age) with a severe stress or adjustment disorder (ICD-10) between 1995 and 2011 (n= 11 292) were followed prospectively for an average of 5.8 years. Incident depressive, anxiety and behavioural disorder diagnoses were examined relative to an age- and gender-matched comparison cohort (n= 56 460) using Cox proportional hazards regression models. Effect modification by gender was examined through stratified analyses.ResultsAll severe stress and adjustment disorder diagnoses were associated with increased rates for all incident outcome disorders relative to the comparison cohort. For instance, adjustment disorders were associated with higher rates of incident depressive (rate ratio RR = 6.8; 95% CI 6.0–7.7), anxiety (RR = 5.3; 95% CI 4.5–6.4), and behavioural disorders (RR = 7.9; 95% CI 6.6–9.3). Similarly, PTSD was also associated with higher rates of depressive (RR = 7.4; 95% CI 4.2–13), anxiety (RR = 7.1; 95% CI 3.5–14) and behavioural disorder (RR = 4.9; 95% CI 2.3–11) diagnoses. There was no evidence of gender-related differences.ConclusionsStress disorders varying in symptom constellation and severity are associated with a range of incident psychiatric disorders in children. Transdiagnostic assessments within a longitudinal framework are needed to characterise the course of post-trauma or severe stressor psychopathology.

The CHA2DS2-VASc score is used to predict stroke risk among patients with atrial fibrillation (AF). We examined whether a CHA2DS2-VASc score predicts stroke risk among individuals without hospital-diagnosed AF and quantified the magnitude of the association in comparison to AF patients. We used data from population-based medical registries (1995 to 2005) covering all Danish hospitals to identify patients diagnosed with AF (n = 122,980). We matched ≤5 non-AF individuals (n = 612,723) to each AF patient on the individual risk factors included in the CHA2DS2-VASc score. We calculated 10-year absolute risk of ischemic and all-cause stroke in AF and non-AF individuals and compared the stroke risk between cohorts within strata of CHA2DS2-VASc scores using Cox regression. The 10-year risk of ischemic/all-cause stroke was 4.4%/8.8% among non-AF individuals and 6.2%/12% in AF patients, corresponding to a risk difference of 1.8% for ischemic stroke and 3.3% for all-cause stroke. In both cohorts, the stroke risk correlated with increasing CHA2DS2-VASc scores. However, in individuals with CHA2DS2-VASc scores ≥5 who were 2DS2-VASc score was associated with 10-year stroke risk also among individuals without hospital-diagnosed AF. In conclusion, primary prophylactic anticoagulation therapy may be relevant in male and younger non-AF individuals with CHA2DS2-VASc scores ≥5. These findings should be confirmed in clinical trials.

Background: The aim of this study was to compare changes in health service utilization, preventive medical management, and cholesterol levels in patients without coronary artery disease (CAD) or with non-obstructive CAD as determined by coronary computed tomography angiography (CTA). Methods: Single-center five-year observational registry-based cohort study of consecutive patients with chest pain undergoing coronary CTA with subsequent 12 months follow-up in general practice. Results: We included 3032 patients with a normal test result (n = 2179) or a diagnosis of non-obstructive CAD (n = 853) by coronary CTA. Median age was 55 (interquartile range: 47–63) years and 44% were males. After coronary CTA, the probability of a decrease in consultations with general practitioner was higher in patients with no CAD compared to patients with non-obstructive CAD (adjusted OR = 0.81 [95% CI: 0.68–0.96], P = 0.016). Accordingly, patients with non-obstructive CAD more frequently received prescriptions on lipid-lowering medical therapy (adjusted OR = 4.50 [95% CI: 3.31–6.12], P < 0.001) than patients with no CAD after coronary CTA. In patients with non-obstructive CAD, mean total-cholesterol reduction was 0.51 (P < 0.001) compared to 0.13 mmol/L (P < 0.001) in patients without non-obstructive CAD. The relative reduction in low-density lipoprotein was 14% higher (P < 0.001) in patients with compared to patients without non-obstructive CAD after coronary CTA. Conclusions: Coronary CTA with subsequent follow-up in general practice has the potential to align health service utilization that prioritizes high-risk patients and facilitate optimized preventive management.

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.

Background Posttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known. Methods In a cohort of adult Danish-born residents of Denmark with an incident diagnosis of unspecified reaction to severe stress (“unspecified stress reaction”) between 1995 and 2011 (N = 24,534), we assessed incidence of seven arterial and venous cardiovascular events/conditions between 1996 and 2013. We calculated standardized incidence ratios (SIRs) comparing incidence of each outcome among the cohort to expected incidence based on sex-, age-, and calendar-time-specific national rates. We conducted stratified analyses by demographic characteristics, comorbidities, and length of follow-up time. Results Incidence over the study period ranged from 1.1% for provoked VTE to 5.7% for stroke, adjusting for competing risk of death. Unspecified stress reaction was associated with all outcomes (SIRs ranging from 1.3, 95% confidence interval (CI): 1.1–1.4 for atrial fibrillation/flutter to 1.9, 95% CI: 1.7–2.2 for unprovoked VTE and 1.9, 95% CI: 1.6–2.3 for provoked VTE). Associations persisted, but were attenuated, when restricting to persons without alcohol use disorder and to persons without physical health comorbidities. Limitations Unspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders. Conclusions Our results augment literature on stress disorders and cardiovascular disease by highlighting the additional importance of unspecified stress disorders. Further research on this diagnostic category, which may represent subsyndromal psychopathology, is warranted. These findings support considering persons with non-specific stress-related psychopathology in treatment and tertiary prevention activities.

Introduction:The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality.Methods:A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects.Results:The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74–2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39–5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94–2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07–1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00–1.73).Conclusion:Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.

PURPOSE: The prevalence of breast cancer survivors has increased due to dissemination of population-based mammographic screening and improved treatments. Recent changes in anti-hormonal therapies for breast cancer may have modified the risks of subsequent urological and genital cancers. We examine the risk of subsequent primary urological and genital cancers in patients with incident breast cancer compared with risks in the general population.METHODS: Using population-based Danish medical registries, we identified a cohort of women with primary breast cancer (1990-2017). We followed them from one year after their breast cancer diagnosis until any subsequent urological or genital cancer diagnosis. We computed incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national incidence rates (by sex, age, and calendar year).RESULTS: Among 84,972 patients with breast cancer (median age 61 years), we observed 623 urological cancers and 1397 genital cancers during a median follow-up of 7.4 years. The incidence rate per 100,000 person-years was stable during follow-up (83 for urological cancers and 176 for genital cancers). The SIR was increased for ovarian cancer (1.37, 95% CI 1.23-1.52) and uterine cancer (1.37, 95% CI 1.25-1.50), but only during the pre-aromatase inhibitor era (before 2007). Moreover, the SIR of kidney cancer was increased (1.52, 95% CI 1.15-1.97), but only during 2007-2017. The SIR for urinary bladder cancer was marginally increased (1.15, 95% CI 1.04-1.28) with no temporal effects. No associations were observed for cervical cancer.CONCLUSION: Breast cancer survivors had higher risks of uterine and ovarian cancer than expected, but only before 2007, and of kidney cancer, but only after 2007. The risk of urinary bladder cancer was moderately increased without temporal effects, and we observed no association with cervical cancer.

Background Some neurogenerative diseases have been linked to a reduced risk of cancer, but the association between motor neuron disease and cancer risk is not well understood. We hypothesized that cancer risk would be lower among those with motor neuron disease and its most common subtype, amyotrophic lateral sclerosis. Methods We conducted a population-based cohort study of motor neuron disease and cancer risk using routinely collected data from population-based registries in Denmark. We examined cancer incidence among patients diagnosed with motor neuron disease between January 1980 and December 2013 followed through 2013. Using Danish national cancer rates for the study period, we computed standardized incidence ratios as a measure of relative risks. Results In the cohort of 5053 patients with a motor neuron disease, the overall standardized incidence ratio of any cancer was 1.17 (95% confidence interval [CI], 1.03–1.31); the corresponding standardized incidence ratio for amyotrophic lateral sclerosis was 1.24 (95% CI, 0.96–1.57). The standardized incidence ratios of any cancer in the cohort with motor neuron disease was 1.52 (95% CI, 1.22–1.87) for 5 years of follow-up. Beyond one year of follow-up, patients in the motor neuron disease had elevated standardized incidence ratios for lymphoid leukemia, non-Hodgkin lymphoma, and basal cell skin cancer. Conclusion Findings fail to support the hypothesis that motor neuron disease or amyotrophic lateral sclerosis is associated with reduced cancer incidence. An elevated risk of cancer during the first year of follow-up may be attributable to heightened surveillance.

ObjectiveWe examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population.DesignUsing population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990–2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs).ResultsAmong 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2–5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6–10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990–2006 and 2007–2017, the 1–10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible.ConclusionBreast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.

ObjectiveAspirin may increase the risk of lower gastrointestinal bleeding (LGIB) from precursors of colorectal cancer (CRC). We investigated whether use of low-dose aspirin, through initiation of LGIB, may lead patients to undergo colonoscopy and polypectomy before manifest CRC.DesignWe conducted a historical cohort study (2005–2013) of all Danish residents who initiated low-dose aspirin treatment (n=412 202) in a setting without screening for CRC. Each new aspirin user was matched with three non-users (n=1 236 560) by age, sex and region of residence on the date of their matched new user’s first-time aspirin prescription (index date). We computed absolute risks (ARs), risk differences and relative risks (RRs) of LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC, comparing aspirin users with non-users.ResultsThe ARs were higher for new users than non-users for LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC within 3 months after index. Comparing new users with non-users, the RRs were 2.79 (95% CI 2.40 to 3.24) for LGIB, 1.73 (95% CI 1.63 to 1.84) for lower gastrointestinal endoscopy, 1.56 (95% CI 1.42 to 1.72) for colorectal polyps and 1.73 (95% CI 1.51 to 1.98) for CRC. The RRs remained elevated for more than 12 months after the index date, with the exception of CRC where the RRs were slightly decreased during the 3–5 years (RR 0.90, 95% CI 0.83 to 0.98) and more than 5 years (RR 0.91, 95% CI 0.82 to 1.00) following the index date.ConclusionThese findings indicate that aspirin may contribute to reduce CRC risk by causing premalignant polyps to bleed, thereby expediting colonoscopy and polypectomy before CRC development.

Background: An elevated erythrocyte sedimentation rate (ESR) may be a marker of occult cancer. Methods: We linked Danish medical databases to examine cancer incidence in patients with a first-time hospital contact for elevated ESR during 1980 to 2013. We calculated standardized incidence ratios (SIR) of cancer compared with the general population, and comorbidity-adjusted HRs (aHR) versus matched population comparisons without elevated ESR. We also compared survival among patients with cancer with elevated ESR with that among patients with cancer without elevated ESR. Results: During median follow-up of 4.9 years, we observed 3,926 cancers among 18,540 patients with a first-time hospital contact for elevated ESR. The risk for any cancer diagnosed during the first year following the contact for elevated ESR was 8.5% [95% confidence interval (CI), 8.1%–8.9%]. The overall 1-year cancer incidence was markedly elevated [SIR 5.3 (95% CI, 5.1–5.6); aHR 5.8 (95% CI, 5.4–6.3)] and was more than 3-fold elevated for most hematologic cancers and for cancers of the peritoneum and connective tissue in the abdominal wall, kidney, and adrenal glands. After the first year, patients were at increased risk of developing especially hematologic cancers. Patients diagnosed with cancer within 1 year after a contact for elevated ESR had poorer survival compared with matched cancer comparisons [adjusted mortality rate ratio 1.2 (95% CI, 1.1–1.3)]. Conclusions: Elevated ESR is a strong marker of undiagnosed cancer and is associated with poorer survival. Impact: Our findings may help clinicians in assessing absolute risk, common sites, and prognosis of cancers discovered after hospital contact with elevated ERS.

Objective The association between thyroid dysfunction and gastrointestinal cancer is unclear. Design We conducted a nationwide population-based cohort study to examine this potential association. Methods We used Danish medical registries to assemble a nationwide population-based cohort of patients diagnosed with hyperthyroid or hypothyroid disease from 1978 to 2013. We computed standardized incidence ratios (SIRs) with corresponding 95% CIs as measures of the relative risk of each cancer, comparing patients with thyroid dysfunction with that expected in the general population. Results We included 163,972 patients, of which 92,783 had hyperthyroidism and 71,189 had hypothyroidism. In general, we found an increased risk of all gastrointestinal cancers within the first year after thyroid disease diagnosis. After more than 5 years of follow-up, patients with hyperthyroidism had a slightly increased risk of pancreatic and gallbladder and biliary tract cancer. Patients with hypothyroidism had a slightly increased risk of stomach, anal, liver, gallbladder and biliary tract, and pancreatic cancer after more than 5 years of follow-up, but the observed numbers of cancers were in general similar to the expected. Conclusions The increased risks of all gastrointestinal cancers in the first year following hyper- or hypothyroidism diagnosis are likely due to detection bias. After more than 5 years of follow-up, there does not seem to be a consistent causal association between thyroid disease and gastrointestinal cancer.

About 10-20% of patients with metastatic colorectal cancer (mCRC) are candidates for metastasis directed therapies such as surgical resection, ablation and stereotactic radiotherapy. We examined the temporal changes in use of metastasis directed therapies and established prognostic factors for survival in a nationwide cohort study. The Danish nationwide medical registries were used to retrieve data on treatment for liver and/or lung metastasis in patients with metastatic colorectal cancer in the period 2000-2013. Overall survival through 2014 was calculated from the time of treatment of metastases by Kaplan-Meier method and mortality between groups was assessed using Cox regression. We report 2,912 patients undergoing a total of 3,602 procedures with an increased use of all modalities during 14 calendar years. Median survival was 3.7 years (interquartile range (IQR) 2.0-9.7 years). In the multivariate analysis, the nodal stage of the primary tumor had the most pronounced association with survival with a hazard ratio for mortality of 1.56 (95% CI: 1.33-1.83) for N2 stage with reference to N0. Furthermore, female gender, age, comorbidity, surgical treatment, administration of chemotherapy, and left-sided primary tumors were associated with improved prognosis in the multivariate analysis.

Background: Respiratory tract bleeding may be a marker of cancer. We quantified the risk of specific cancer types among patients with hospital-based diagnoses of epistaxis and haemoptysis relative to risk in the general population. Methods: We used Danish, nationwide databases to conduct a population-based cohort study of 80460 patients diagnosed with epistaxis and 18487 patients presenting with haemoptysis (1995−2013). We followed patients until a cancer diagnosis, emigration, death, or 31 December 2013, whichever came first. As a measure of the relative risk, we computed standardised incidence ratios (SIRs), as the observed to expected number of cancers based on national cancer incidence rates. Results: The 90-day absolute risk of any cancer was 0.59% in the epistaxis cohort and 3.78% in the haemoptysis cohort. The corresponding SIRs were 1.85 (95% confidence interval (CI) 1.69, 2.02) and 14.6 (95% CI 13.5, 15.7), respectively. The 90-day SIRs were highest for haematological cancers following epistaxis (5.78 (95% CI 4.62, 7.14)), and for smoking and alcohol-related cancers following haemoptysis (36.3 (95% CI 33.5, 39.3)). The cancer risk decreased steadily over time, but persisted beyond 5 years of follow-up after both conditions. Conclusions: Epistaxis and particular haemoptysis may be markers of cancer at several sites.

>= 1 year after PID diagnosis, an elevated risk persists for female genital cancers and smoking-related cancers.

Introduction: Adults with congenital heart disease (CHD) are at increased risk for major adverse cardiovascular events (MACE), including stroke, myocardial infarctions, and heart failure. Following survival of MACE, an important metric of resultant morbidity is re-entry to the workforce. This study sought to characterize the differences in return-to-work (RTW) characteristics between the MACE survivors with CHD and those in the general population without CHD. Methods: By linking Danish health and administrative registries, a cohort of adults with CHD who survived a MACE were matched 1:10 by age …

Background Adults with congenital heart disease (CHD) are at elevated risk of hospitalization for community-acquired pneumonia (CAP). Proton-pump inhibitors (PPIs) have been shown to be a risk factor for CAP in adult and pediatric general populations. This study explored the association between PPI use and subsequent CAP hospitalizations in the adult CHD population. Methods Using the Danish National Patient Registry, we performed a nested case-control study of adults with CHD who had been admitted to the hospital for CAP between 1996 and 2017. The timing and dose of PPI were evaluated in the year preceding the CAP admission. Logistic regression measured the impact of timing and dose of PPI on the subsequent CAP admission. Results In total, 618 adult CHD patients were admitted for CAP during the study period. The adjusted odds ratio (OR) was 2.21 (95% confidence interval (CI) 1.66–2.94) for CAP in current PPI users compared with non-users. The OR amongst current PPI users was further elevated for males, those older than 65 years old and those with severe/univentricular CHD [3.59 (95% CI 2.33–5.52), 2.30 (95% CI 1.55–3.41), 2.35 (95% CI 1.13–4.87)], respectively. Segmenting by dose, the OR for CAP patients taking low-dose and high-dose PPI was 2.11 (95% CI 1.38–3.22) and 2.29 (95% CI 1.60–3.26), respectively. Conclusions Adults with CHD prescribed a PPI are at elevated risk of hospitalization for CAP in the following 90 days. The risk for CAP admission is further increased for those prescribed high-dose PPIs, males, those older than 65 years of age, and those with severe/univentricular CHD.

BACKGROUND: Evidence for the association between posttraumatic stress disorder (PTSD) and gastrointestinal (GI) disorders is mixed, owing in part to methodologic differences across studies. Furthermore, studies which have combined GI disorders or symptoms for examination as one overall category may potentially obscure associations between PTSD and individual GI diagnoses.METHODS: This nationwide cohort study examined the incidence of all major nonmalignant GI disorders in patients with a prior PTSD diagnosis (n = 4,076), compared with the general population incidence from 1995 to 2013, using Danish medical registry data. We examined differences by sex, age, marital status, psychiatric and somatic comorbidity, and follow-up time. Risks, standardized incidence rates (SIRs), and confidence intervals (95% CIs) were calculated.RESULTS: Risk of any GI disorder among PTSD patients was 25% (95% CI: 21%, 29%); the SIR for any GI disorder was 1.8 (95% CI: 1.7, 2.0). Risk and SIRs varied by disorder (e.g., no association with diverticula of the intestines [SIR: 1.1, 95% CI: 0.83, 1.5]; stronger association with peptic ulcer, site unspecified [SIR: 3.3, 95% CI: 1.8, 5.5]). Stratified analyses revealed that some associations were stronger for persons ages 16-39 or unmarried at PTSD diagnosis, persons with comorbid psychiatric diagnoses, and in the year following PTSD diagnosis.CONCLUSIONS: This study documents associations between clinician-diagnosed PTSD and all major nonmalignant GI disorders in an unselected nationwide cohort with long follow-up. Differences in associations across GI disorders and important modifiers may account for previous conflicting research findings.

BACKGROUND: It is unknown whether posttraumatic stress disorder (PTSD) is associated with incident infections. This study’s objectives were to examine (1) the association between PTSD diagnosis and 28 types of infections and (2) the interaction between PTSD diagnosis and sex on the rate of infections. METHODS: The study population consisted of a longitudinal nationwide cohort of all residents of Denmark who received a PTSD diagnosis between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We fit Cox proportional hazards regression models to examine associations between PTSD diagnosis and infections. To account for multiple estimation, we adjusted the hazard ratios using semi-Bayes shrinkage. We calculated interaction contrasts to assess the presence of interaction between PTSD diagnosis and sex. RESULTS: After semi-Bayes shrinkage, the hazard ratio (HR) for any type of infection was 1.8 [95% confidence interval (CI: 1.6, 2.0)], adjusting for marital status, non-psychiatric comorbidity, and diagnoses of substance abuse, substance dependence, and depression. The association between PTSD diagnosis and some infections (e.g., urinary tract infections) were stronger among women whereas other associations were stronger among men (e.g., skin infections). CONCLUSIONS: This study’s findings suggest that PTSD diagnosis is a risk factor for numerous infection types and that the associations between PTSD diagnosis and infections are modified by sex.

Aims Implantable cardioverter-defibrillator (ICD) treatment prevents sudden cardiac death in high-risk patients. This study examined geographical variation in ICD implantation rates in Denmark and potential causes of variation. Methods and results We obtained numbers of ICD implantations in the 5 Danish regions and 98 municipalities during 2007–13 from the Danish Pacemaker and ICD Registry. Standardized implantation rates (SIRs) were computed as ICD implantations per 1 000 000 person-years, and age- and gender-standardized to the Danish population. We examined associations of the municipal SIR with mean age and Charlson Comorbidity Index score of ICD recipients, percentage of implantations with primary prophylactic indication, and distance from patient residency to ICD implanting centre. Based on 7192 ICD implantations, the nationwide SIR was 186 [95% confidence interval (CI) 182–190], ranging from 170 (95% CI 158–183) in the North Denmark Region to 206 (95% CI 195–218) in the Region of Zealand. Municipalities with higher patient comorbidity scores, higher percentages of implantations with primary prophylactic indication, and shorter distances to ICD implanting centres, had higher SIRs [differences between SIRs of municipalities in highest and lowest quartiles 22 (95% CI 10–34), 45 (95% CI 33–58), and 35 (95% CI 24–47), respectively]. Regional differences in SIRs decreased over time and had become insignificant during 2011–13. Conclusion Implantable cardioverter-defibrillator implantation rates in Denmark varied significantly between regions but variation decreased during 2007–13. Geographical variation was associated with differences in patient comorbidity score, variation in use of primary prophylactic ICD treatment, and distance to ICD implanting centre.

BACKGROUND:Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection.STUDY QUESTION:To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients.STUDY DESIGN:Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date.MEASURES AND OUTCOMES:We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers.RESULTS:We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed.CONCLUSIONS:These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.

The CHA

INTRODUCTION: There is little evidence about gastrointestinal (GI) disorders in patients with schizophrenia. We examined association of schizophrenia with upper GI bleeding (UGIB) and nonbleeding ulcers and associated risk factors and mortality.METHODS: We used the data linked from population-based registries in Denmark. Among patients with incident schizophrenia in 1980-2011, we computed cumulative incidences and standardized incidence ratios of UGIB, bleeding ulcers, and nonbleeding ulcers compared with the general population; evaluated risk factors for the 3 GI endpoints, including somatic and psychiatric comorbidity; and examined subsequent all-cause mortality.RESULTS: Among 39,998 patients with schizophrenia, the standardized incidence ratios were 2.92 (95% confidence interval (CI), 2.76-3.08) for UGIB, 2.36 (95% CI, 2.15-2.58) for bleeding ulcers, and 2.00 (95% CI, 1.87-2.15) for nonbleeding ulcers. Risk factors for UGIB and nonbleeding ulcers included age, somatic comorbidity, and medication use. UGIB and nonbleeding ulcers were associated with the subsequent increase in mortality.CONCLUSIONS: Schizophrenia is associated with an increased risk of UGIB and nonbleeding ulcers, whose risk factors in patients with schizophrenia are similar to those in the general population.

Introduction: Adults with congenital heart disease (CHD) are at elevated risk of hospital admission for community-acquired pneumonia (CAP) with elevated length-of-stay and 30-day mortality than the general population. Proton-pump inhibitors (PPIs) have been shown to be a risk factor for CAP in adult and pediatric general populations. This study explored the association between PPI use and CAP in the adult CHD population. Methods: Using the Danish National Patient Registry and the Danish Register of Congenital …

In patients with systemic mastocytosis (SM), several aspects of morbidity remain poorly understood. We assessed the risk of solid cancers, cardiovascular disease, anaphylaxis, osteoporosis, and fractures in SM patients. Using Danish medical registries, we conducted a nationwide population-based cohort study including 687 adult (≥15 years) SM patients diagnosed during 1997-2012. A comparison cohort of 68,700 subjects from the general Danish population who were alive and without SM at the given SM subject's diagnosis were age- and gender-matched. Outcomes were a new diagnosis of solid cancer, venous thromboembolism (VTE), myocardial infarction (MI), stroke, anaphylaxis, osteoporosis, or fracture. For solid cancers the hazard ratio (HR) was 2.4 (95% confidence interval [CI] 1.9-2.8) with a 10-year absolute risk (AR) in the SM-cohort of 12.6% (95% CI 9.4-16.3). Specifically, we found a HR of 7.5 (95% CI 4.4-13.0) for melanoma and a HR of 2.5 (95% CI 1.7-3.5) for non-melanoma skin cancers (NMSCs). For VTE we found a HR of 1.9 (95% CI 1.2-3.0), with a 10-year AR of 3.9% (95% CI 2.3-6.1); for MI a nonsignificant increased HR of 1.4 (95% CI 0.9-2.3), with a 10-year AR of 1.8% (95% CI 0.9-3.2); and for stroke a HR of 1.6 (95% CI 1.1-2.3) with a 10-year AR of 4.6% (95% CI 2.8-6.9). The HR for anaphylaxis was 7.2 (95% CI 5.3-9.9), and the 10-year AR was 3.1% (95% CI 1.9-4.9). For osteoporosis the HR was 3.6 (95% CI 2.7-4.6) with a 10-year AR of 7.2% (95% CI 5.2-9.8). For fractures the HR was 1.2 (95% CI 0.9-1.6) and the 10-year AR was 5.9% (95% CI 3.9-8.4). SM patients are at increased risk of solid cancers - especially melanoma and NMSC-and cardiovascular disease. The risk of anaphylaxis and osteoporosis is clearly increased in SM, though absolute risk was low in this population-based study. The fracture-risk was only slightly increased. Am. J. Hematol. 91:1069-1075, 2016. © 2016 Wiley Periodicals, Inc.

Background Elevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl. Methods We conducted a population-based cohort study using data from Danish medical registries during 1998–2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200–600pmol/L (reference/normal range), 601–800pmol/L and >800pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan–Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index. Results Survival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200–600pmol/L: 69.3%; 601–800pmol/L: 49.6%; >800pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601–800pmol/L or >800pmol/L, compared to patients with levels of 200–600pmol/L [(MRR (95% confidence interval): 601–800pmol/L vs. 200–600pmol/L: 1.9 (1.6–2.2); >800pmol/L vs. 200–600pmol/L: 2.7 (2.4–3.1)]. This association remained robust for 31–90-day and 91–365-day mortality, showing similar dose-response patterns. Conclusion Cancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.

Vaginal bleeding in early pregnancy is not associated with a higher cancer risk compared with pregnancies in women from the general population of similar age.