ObjectiveTo examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort.DesignNationwide, population based cohort study.SettingAll Danish hospitals and hospital outpatient clinics from 1995 to 2013.Participants51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year.Main outcome measuresComorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis.ResultsHigher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking.ConclusionsMigraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases.

Objective: We aimed to investigate the impact of hyponatremia severity on mortality risk and assess any evidence of a dose-response relation, utilizing prospectively collected data from population-based registries. Design: Cohort study of 279 508 first-time acute admissions to Departments of Internal Medicine in the North and Central Denmark Regions from 2006 to 2011. Methods: We used the Kaplan-Meier method (1 -survival function) to compute 30-day and 1-year mortality in patients with normonatremia and categories of increasing hyponatremia severity. Relative risks (RRs) with 95% CIs, adjusted for age, gender and previous morbidities, and stratified by clinical subgroups were estimated by the pseudo-value approach. The probability of death was estimated treating serum sodium as a continuous variable. Results: The prevalence of admission hyponatremia was 15% (41 803 patients). Thirty-day mortality was 3.6% in normonatremic patients compared to 7.3, 10.0, 10.4 and 9.6% in patients with serum sodium levels of 130-134.9, 125-129.9, 120-124.9 and !120 mmol/l, resulting in adjusted RRs of 1.4 (95% CI: 1.3-1.4), 1.7 (95% CI: 1.6-1.8), 1.7 (95% CI: 1.4-1.9) and 1.3 (95% CI: 1.1-1.5) respectively. Mortality risk was increased across virtually all clinical subgroups, and remained increased by 30-40% 1 year after admission. The probability of death increased when serum sodium decreased from 139 to 132 mmol/l. No clear increase in mortality was observed for lower concentrations. Conclusions: Hyponatremia is highly prevalent among patients admitted to Departments of Internal Medicine and is associated with increased 30-day and 1-year mortality risk, regardless of underlying disease. This risk seems independent of hyponatremia severity.

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SUMMARY BackgroundBleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear.

ObjectiveTo examine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes for hyponatraemia in the nationwide population-based Danish National Registry of Patients (DNRP) among inpatients of all ages.DesignPopulation-based validation study.SettingAll somatic hospitals in the North and Central Denmark Regions from 2006 through 2011.Participants:Patients of all ages admitted to hospital (n=819 701 individual patients) during the study period. The patient could be included in the study more than once, and our study did not restrict to patients with serum sodium measurements (total of n=2 186 642 hospitalisations).Main outcome measureWe validated ICD-10 discharge diagnoses of hyponatraemia recorded in the DNRP, using serum sodium measurements obtained from the laboratory information systems (LABKA) research database as the gold standard. One sodium value <135 mmol/L measured at any time during hospitalisation confirmed the diagnosis. We estimated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ICD-10 codes for hyponatraemia overall and for cut-off points for increasing hyponatraemia severity.ResultAn ICD-10 code for hyponatraemia was recorded in the DNRP in 5850 of the 2 186 642 hospitalisations identified. According to laboratory measurements, however, hyponatraemia was present in 306 418 (14%) hospitalisations. Sensitivity of hyponatraemia diagnoses was 1.8% (95% CI 1.7% to 1.8%). For sodium values <115 mmol/L, sensitivity was 34.3% (95% CI 32.6% to 35.9%). The overall PPV was 92.5% (95% CI 91.8% to 93.1%) and decreased with increasing hyponatraemia severity. Specificity and NPV were high for all cut-off points (≥99.8% and ≥86.2%, respectively). Patients with hyponatraemia without a corresponding ICD-10 discharge diagnosis were younger and had higher Charlson Comorbidity Index scores than patients with hyponatraemia with a hyponatraemia code in the DNRP.ConclusionsICD-10 codes for hyponatraemia in the DNRP have high specificity but very low sensitivity. Laboratory test results, not discharge diagnoses, should be used to ascertain hyponatraemia.

ObjectiveTo investigate the completeness of tumor, node, and metastasis (TNM) staging for invasive bladder cancer in the Danish Cancer Registry (DCR).MethodsFrom the DCR, we retrieved data on TNM stage, year of diagnosis, sex, and age of all-incident invasive bladder cancer patients between 2004 and 2009. Data on comorbidity was obtained from the Danish National Patient Register. We estimated the completeness of TNM registration in the DCR overall and stratified the analysis by sex, age, year of cancer diagnosis, and Charlson comorbidity score. Through knowledge of pathophysiology and clinical coding practice, we designed a clinically based algorithm that allowed tumors with certain missing TNM-stage components to be placed in localized, regional, distant, and unknown categories.ResultsThe overall completeness of TNM staging for bladder cancer was 44.1% (95% confidence interval [CI]: 42.7–45.5). Completeness decreased from 60.9% (95% CI: 40.6–78.6) in patients aged 0–39 years to 25.5% (95% CI: 23.2–27.9) in patients aged 80 years or older. Among patients with a low level of comorbidity, completeness was 48.4% (95% CI: 46.6–50.3), decreasing to 34.0% (95% CI: 30.4–37.8) among those with a high level of comorbidity. The highest proportion of missing TNM data was found for registration of lymph node metastases. Defining T1 cancer as completely registered, regardless of missing N and M stage, increased TNM-registration completeness to 61.8%. When we applied a clinically based algorithm, only 29.6% of tumors had an unknown stage.ConclusionThe overall completeness of TNM staging for bladder cancer in the DCR was low, especially with increasing age and high level of comorbidity. Thus, restricting analyses to bladder cancer patients with complete data on stage may produce substantially selected study populations. Careful considerations should thus be made on handling missing data.

A diagnosis of hyponatremia may be a marker of occult neoplasms, especially cancers of the lung, brain, liver, pancreas, esophagus, kidney, pharynx and non-Hodgkin lymphoma. Hyponatremia may aid in early detection of cancer.

Diuretic use except from thiazides, and particularly if newly initiated, is a negative prognostic factor in patients admitted with hyponatremia.