Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study

INTRODUCTION. Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women. METHODS. We used Danish registries to identify 5,565 postmenopausal women diagnosed with incident invasive breast carcinoma between 1 January 1991 and 31 December 2007, and 55,650 matched population controls. Cardiac glycoside prescriptions were ascertained from county prescription registries. All subjects had at least 2 years of recorded prescription drug and medical history data. We estimated the odds ratio associating digoxin use with breast cancer in conditional logistic regression models adjusted for age, county of residence, and use of anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and hormone replacement therapy. We also explored the impact of confounding by indication and detection bias. RESULTS. Digoxin was the sole cardiac glycoside prescribed to subjects during the study period. There were 324 breast cancer cases (5.8%) and 2,546 controls (4.6%) with a history of digoxin use at least 1 year before their index date (adjusted odds ratio (OR): 1.30; 95% confidence interval: 1.14 to 1.48). The breast cancer OR increased modestly with increasing duration of digoxin exposure (adjusted OR for 7 to 18 years of digoxin use: 1.39; 95% confidence interval: 1.10 to 1.74). The association was robust to adjustment for age, receipt of hormone replacement therapy, coprescribed drugs, and confounding by indication. A comparison of screening mammography rates between cases and controls showed no evidence of detection bias. CONCLUSIONS. Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.Congressionaly Directed Medical Research Programs (BC073012); Karen Elise Jensen Foundation; Western Danish Research Forum for Health Science

Short-term mortality after perforated or bleeding peptic ulcer among elderly patients: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Mortality after perforated and bleeding peptic ulcer increases with age. Limited data exist on how the higher burden of comorbidity among elderly patients affects this association. We aimed to examine the association of age with short-term mortality after perforated and bleeding peptic ulcer and to determine the impact of comorbidity on this association.</p> <p>Methods</p> <p>In this population-based cohort study in three Danish counties between 1991 and 2003 we identified two cohorts of patients: those hospitalized with a first-time discharge diagnosis of perforated peptic ulcer and those with bleeding peptic ulcer. The diagnoses were ascertained from hospital discharge registries and mortality through the Danish Civil Registration System. Information on comorbidity and use of ulcer-related drugs was obtained through administrative medical databases. We computed age-, gender- and comorbidity-standardized 30-day mortality rates and used Cox's regression to estimate adjusted 30-day mortality rate ratios (MRR) for elderly compared with younger patients.</p> <p>Results</p> <p>Among 2,061 patients with perforated peptic ulcer, 743 (36%) were 65–79 years old and 513 patients (25%) were aged 80+ years. Standardized 30-day mortality was 8.9% among patients younger than 65 years rising to 44.6% among patients aged 80+ years, corresponding to an adjusted MRR of 5.3 (95% CI: 4.0–7.0). Among 7,232 patients with bleeding peptic ulcer 2,372 (33%) were aged 80+ years. Standardized 30-day mortality among patients younger than 65 was 4.3% compared with 16.9% among patients aged 80+ years, corresponding to an adjusted MRR of 3.7 (95% CI: 2.9–4.7). Analyses stratified by comorbidity consistently showed high MRRs among elderly patients, regardless of comorbidity level.</p> <p>Conclusion</p> <p>Ageing is a strong predictor for a poor outcome after perforated and bleeding peptic ulcer independently of comorbidity.</p

The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients

<p>Abstract</p> <p>Background</p> <p>The Charlson comorbidity index is often used to control for confounding in research based on medical databases. There are few studies of the accuracy of the codes obtained from these databases.</p> <p>We examined the positive predictive value (PPV) of the ICD-10 diagnostic coding in the Danish National Registry of Patients (NRP) for the 19 Charlson conditions.</p> <p>Methods</p> <p>Among all hospitalizations in Northern Denmark between 1 January 1998 and 31 December 2007 with a first-listed diagnosis of a Charlson condition in the NRP, we selected 50 hospital contacts for each condition. We reviewed discharge summaries and medical records to verify the NRP diagnoses, and computed the PPV as the proportion of confirmed diagnoses.</p> <p>Results</p> <p>A total of 950 records were reviewed. The overall PPV for the 19 Charlson conditions was 98.0% (95% CI; 96.9, 98.8). The PPVs ranged from 82.0% (95% CI; 68.6%, 91.4%) for diabetes with diabetic complications to 100% (one-sided 97.5% CI; 92.9%, 100%) for congestive heart failure, peripheral vascular disease, chronic pulmonary disease, mild and severe liver disease, hemiplegia, renal disease, leukaemia, lymphoma, metastatic tumour, and AIDS.</p> <p>Conclusion</p> <p>The PPV of NRP coding of the Charlson conditions was consistently high.</p

Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding:A Danish population-based cohort study

OBJECTIVES: We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). METHODS: This population‐based cohort study used data from Danish health registries. We identified all patients with a first‐time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person‐years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA(2)DS(2)VASc score, and Charlson Comorbidity Index score. RESULTS: We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow‐up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1‐1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2‐2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7–1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1‐2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1‐4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3–2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7–3.9). CONCLUSION: In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications

Partner Bereavement and Risk of Herpes Zoster: Results from Two Population-Based Case-Control Studies in Denmark and the United Kingdom.

Background: Psychological stress is commonly thought to increase the risk of herpes zoster by causing immunosuppression. However, epidemiological studies on the topic are sparse and inconsistent. We conducted 2 parallel case-control studies of the association between partner bereavement and risk of zoster using electronic healthcare data covering the entire Danish population and general practices in the UK Clinical Practice Research Datalink. Methods: We included patients with a zoster diagnosis from the primary care or hospital-based setting in 1997-2013 in Denmark (n = 190671) and 2000-2013 in the United Kingdom (n = 150207). We matched up to 4 controls to each case patient by age, sex, and general practice (United Kingdom only) using risk-set sampling. The date of diagnosis was the index date for case patients and their controls. We computed adjusted odds ratios with 99% confidence intervals for previous bereavement among case patients versus controls using conditional logistic regression with results from the 2 settings pooled using random-effects meta-analysis. Results: Overall, the adjusted odds ratios for the association between partner bereavement and zoster were 1.05 (99% confidence interval, 1.03-1.07) in Denmark and 1.01 (.98-1.05) in the United Kingdom. The pooled estimates were 0.72, 0.90, 1.10, 1.08, 1.02, 1.04, and 1.03 for bereavement within 0-7, 8-14, 15-30, 31-90, 91-365, 366-1095, and >1095 days before the index date, respectively. Conclusions: We found no consistent evidence of an increased risk of zoster after partner death. Initial fluctuations in estimates may be explained by delayed healthcare contact due to the loss

Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers

Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994-2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori-related) and gastric ulcers (dominantly lifestyle-related) compared with the general population. We started follow-up 1-year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1-5-year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31-1.44) and 1.30 (95% CI: 1.23-1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking- and alcohol-related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized

Linkage between the Danish National Health Service Prescription Database, the Danish Fetal Medicine Database, and other Danish registries as a tool for the study of drug safety in pregnancy

A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004), the Danish Fetal Medicine Database, the Danish National Registry of Patients, and the Medical Birth Registry. The new linked database will provide validated information on malformations diagnosed both prenatally and postnatally. The cohort from 2008 to 2014 will comprise 589,000 pregnancies with information on 424,000 pregnancies resulting in live-born children, ∼420,000 pregnancies undergoing prenatal ultrasound scans, 65,000 miscarriages, and 92,000 terminations. It will be updated yearly with information on ∼80,000 pregnancies. The cohort will enable identification of drug exposures associated with severe malformations, not only based on malformations diagnosed after birth but also including those having led to termination of pregnancy or miscarriage. Such combined data will provide a unique source of information for research on the safety of medications used during pregnancy