Preadmission Diuretic Use and Mortality in Patients Hospitalized With Hyponatremia: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It is uncertain whether diuretic use is linked to mortality risk in patients with hyponatremia. STUDY QUESTION: To measure the prognostic impact of diuretic use on 30-day mortality among patients hospitalized with hyponatremia. STUDY DESIGN: Using population-based registries, we identified all patients with a serum sodium measurement <135 mmol/L within 24 hours after acute hospital admission in western Denmark from 2006 to 2012 (cumulative population of 2.2 million). We categorized patients as current diuretic users (new and long-term), former users or nonusers, and followed them until death, migration or up to 30 days which ever came first. MEASURES AND OUTCOMES: Thirty-day cumulative mortality and relative risk with 95% confidence interval (CI) controlled for demographics, previous morbidity, renal function, and co-medications. Calculations were also divided by the diuretic type and were repeated after propensity score matching. RESULTS: Thirty-day mortality was 11.4% among current diuretic users (n = 14,635) compared with 6.2% among nonusers, yielding an adjusted relative risk of 1.4 (95% CI, 1.2-1.5). New users were at higher risk (1.7, 95% CI, 1.5-2.0) than long-term users (1.3, 95% CI, 1.2-1.4). In particular, the use of loop diuretics (1.6, 95% CI, 1.4-1.8), potassium-sparing diuretics (1.6, 95% CI, 1.2-2.2), and diuretic polytherapy (1.5, 95% CI, 1.3-1.7) were associated with increased risk, whereas thiazide use was not (1.0, 95% CI, 0.9-1.2). Propensity score-matched analyses confirmed the results. CONCLUSIONS: Diuretic use except from thiazides, and particularly if newly initiated, is a negative prognostic factor in patients admitted with hyponatremia.

Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.

OBJECTIVE: To 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. DESIGN: Nationwide, population based cohort study. SETTING: All Danish hospitals and hospital outpatient clinics from 1995 to 2013. PARTICIPANTS: 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. MAIN OUTCOME MEASURES: Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. RESULTS: Higher 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. CONCLUSIONS: Migraine 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.

Diagnosis of hyponatremia and increased risk of a subsequent cancer diagnosis: results from a nationwide population-based cohort study.

BACKGROUND: Hyponatremia has recently been associated with subsequent cancer risk. This population-based nationwide study assessed whether the diagnosis of hyponatremia can predict a cancer diagnosis within most common cancers. MATERIAL AND METHODS: Using Danish medical registries, we identified 16,220 patients with a first-time diagnosis of hyponatremia, without a cancer diagnosis, from January 2006 through November 2013. We quantified the relative risk of a subsequent cancer diagnosis by standardized incidence ratios (SIRs), comparing observed cancer incidence among patients diagnosed with hyponatremia to that expected, based on national cancer incidence during that period. RESULTS: During 40,207 person-years of follow-up, we observed 1546 cancer diagnoses compared to 956 expected (SIR: 1.62; 95% confidence interval (CI), 1.54-1.70). The increase in risk of a cancer diagnosis following a hyponatremia diagnosis was most pronounced within 0-6 months of follow-up (SIR 4.16; 95% CI, 3.85-4.48) and in the younger age group; 0-29 years (SIR 8.71; 95% CI, 2.82-20.28), 30-49 years (SIR 3.16; 95% CI, 2.26-4.31), 50-69 years (SIR 2.29; 95% CI, 2.10-2.48) and 70 + years (SIR 1.35; 95% CI, 1.27-1.44). Within six months after a hyponatremia diagnosis, the SIRs increased 10-fold for cancers of the lung (SIR 17.14; 95% CI, 15.15-19.32), brain (SIR 13.52; 95% CI, 8.90-19.66) and liver (SIR 13.26; 95% CI, 7.57-21.53) and increased 5 to 10-fold for cancers of the pancreas (SIR 8.25; 95% CI, 5.72-11.53), esophagus (SIR 6.59; 95% CI, 3.15-12.12), kidney (SIR 6.36; 95% CI, 3.39-10.88), pharynx (SIR 6.15; 95% CI, 1.27-17.97) and non-Hodgkin lymphoma (SIR 6.10; 95% CI, 4.17-8.61). The rate increased across virtually all types of cancers, except melanoma and basal cell carcinomas. CONCLUSIONS: 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.

Hyponatremia and mortality risk: a Danish cohort study of 279 508 acutely hospitalized patients.

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.

Positive predictive value of primary inpatient discharge diagnoses of infection among cancer patients in the Danish National Registry of Patients.

PURPOSE: Pharmacovigilance studies of cancer treatment frequently monitor infections. Predictive values of algorithms identifying disease depend on prevalence of the disease in the population under study. We therefore estimated the positive predictive value (PPV) of primary inpatient diagnosis of infection among cancer patients in the Danish National Registry of Patients (DNRP). METHODS: The algorithm to identify infections in the DNPR was based on International Classification of Diseases, 10th revision (ICD-10) codes. A physician blinded to the type of sampled infection reviewed the medical charts and assessed the presence and type of infection. Using the physician global assessment as gold standard, we computed PPVs with and without requiring agreement on infection type. RESULTS: We retrieved 266 of 272 medical charts (98%). Presence of infection was confirmed in 261 patients, resulting in an overall PPV of 98% (95% confidence interval, 96%-99%). When requiring agreement on infection type, overall PPV was 77%. For skin infections, pneumonia, and sepsis, PPVs were 79%, 93% and 84%, respectively. For these infections, we additionally calculated PPVs using evidence-based criteria as the gold standard. PPV was similar for pneumonia, but lower for skin infections and sepsis. CONCLUSIONS: The Danish National Registry of Patients is suitable for monitoring infections requiring hospitalization among cancer patients.

Validity of the International Classification of Diseases, 10th revision discharge diagnosis codes for hyponatraemia in the Danish National Registry of Patients.

OBJECTIVE: To 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. DESIGN: Population-based validation study. SETTING: All 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 MEASURE: We 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. RESULT: An 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. CONCLUSIONS: ICD-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.

Completeness of bladder cancer staging in the Danish Cancer Registry, 2004-2009.

OBJECTIVE: To investigate the completeness of tumor, node, and metastasis (TNM) staging for invasive bladder cancer in the Danish Cancer Registry (DCR). METHODS: From 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. RESULTS: The 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. CONCLUSION: The 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.