Correction: Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography.

[This corrects the article DOI: 10.1371/journal.pone.0208645.].

Socioeconomic differences in outcomes after hospital admission for atrial fibrillation or flutter.

AIMS: To examine socioeconomic differences in care and outcomes in a 1-year period beginning 30 days after hospital discharge for first-time atrial fibrillation or flutter (AF) hospitalization. METHODS AND RESULTS: This nationwide register-based follow-up cohort study investigated AF 30-day discharge survivors in Denmark during 2005-2014 and examined associations between patient's socioeconomic status (SES) and selected outcomes during a 1-year follow-up period beginning 30 days post-discharge after first-time hospitalization for AF. Patient SES was defined in four groups (lowest, second lowest, second highest, and highest) according to each patient's equivalized income. SES of the included 150 544 patients was: 27.7% lowest (n = 41 648), 28.1% second lowest (n = 42 321), 23.7% second highest (n = 35 656), and 20.5% highest (n = 30 919). Patients of lowest SES were older and more often women. Within 1-year follow-up, patients of lowest SES were less often rehospitalized or seen in outpatient clinics due to AF, or treated with cardioversion or ablation and were slightly more often diagnosed with stroke and heart failure (HF) and significantly more likely to die (16.1% vs. 14.9%, 11.3% and 8.1%). Hazard ratios for all-cause mortality were 0.64 (95% confidence interval 0.61-0.68) for highest vs. lowest SES, adjusted for CHA2DS2-VASc score, chronic obstructive pulmonary disease, rate- and rhythm-controlling drugs, and cohabitation status. CONCLUSION: In 30-day survivors of first-time hospitalization due to AF, lowest SES is associated with increased 1-year all-cause and cardiovascular mortality and fewer cardioversions, ablations, readmissions, and outpatient contacts due to AF. Our findings indicate a need for socially differentiated rehabilitation following hospital discharge for first-time AF.

Are gain values significantly altered by manual data selection when performing the video Head Impulse Test (v-HIT) on all six semicircular canals with two different v-HIT systems.

BACKGROUND: It has not yet been tested whether averaged gain values and the presence of pathological saccades are significantly altered by manual data selection or if data selection only done by the incorporated software detection algorithms provides a reliable data set following v-HIT testing. OBJECTIVE: The primary endpoint was to evaluate whether the averaged gain values of all six SCCs are significantly altered by manual data selection with two different v-HIT systems. METHOD: 120 subjects with previously neither vestibular nor neurological disorders underwent four separate tests of all six SCCs with either EyeSeeCam® or ICS Impulse®. All v-HIT test reports underwent manual data selection by an experienced ENT Specialist with deletion of any noise and/or artifacts. Generalized estimating equations were used to compare averaged gain values based on unsorted data with averaged gain values based on the sorted data. RESULTS: EyeSeeCam®: Horizontal SCCs: The estimate and the p-value (shown in parenthesis) for the right lateral SCC and the left lateral SCC were 0.00004 (0.95) and 0.00087 (0.70) respectively. Vertical SCCs: The estimate varied from -0.00858 to 0.00634 with p-values ranging from 0.31 to 0.78. ICS Impulse®: Horizontal SCCs: The estimate and the p-value for the right lateral SCC and the left lateral SCC were 0.00159 (0.18) and 0.00071 (0.38) respectively. Vertical SCCs: The estimate varied from 0.00217 to 0.01357 with p-values ranging from 0.00 to 0.17. Based upon the averaged gain value from the individual SCC being tested, 148 tests before and 127 after manual data selection were considered pathological. CONCLUSION: None of the two v-HIT systems revealed any clinically important effects of manual data selection. However, 21 fewer tests were considered pathological after manual data selection.

Uncertainty in classification of death from fatal myocardial infarction: A nationwide analysis of regional variation in incidence and diagnostic support.

AIMS: The usefulness of mortality statistics relies on the validity of death certificate diagnosis. However, diagnosing the causal sequence of conditions leading to death is not simple. We examined diagnostic support for fatal acute myocardial infarction (AMI) and investigated its association with regional variation. METHODS AND RESULTS: From Danish nationwide registers, we identified the study population (N = 3,244,051) of whom 36,669 individuals were recorded with AMI as the underlying cause-of-death between 2002 and 2015. We included clinical diagnoses, procedures, and claimed prescriptions related to atherosclerotic disease to evaluate the level of diagnostic support for fatal AMI in three diagnostic groups (Definite; Plausible; Uncertain). Adjusted mortality rates, rate ratios, and odds ratios were estimated for each AMI category, stratified by hospital region using multivariable regression models. More than one-third (N = 12,827, 35%) of deaths reported as fatal AMI had uncertain diagnostic support. The largest regional variation in AMI mortality rate ratios, varying from 1.16 (95%CI:1.02;1.31) to 1.62 (95%CI:1.43;1.83), was found among cases with uncertain diagnostic supportive data. Substantial inter-regional differences in the degree to which death occurs outside hospital [OR: 1.01 (95%CI:0.92;1.12) - 1.49 (95%CI:1.36;1.63)] and general practitioners determining the cause-of-death at home were present. Minor regional differences [OR: 0.96 (95%CI:0.85;1.07) - 1.16 (95%CI:1.04;1.29)] in in-hospital AMI mortality were observed. CONCLUSION: There is significant regional variation associated with recording AMI as a cause-of-death. This variation is predominately based on death certificate diagnoses without diagnostic supportive evidence. Studies of fatal AMI should include a stratification on supportive evidence of the diagnosis.

Comparison of test results from two separate video head impulse test systems in a cohort of patients diagnosed with a unilateral vestibular schwannoma.

PURPOSE: Video head impulse testing (vHIT) is a relatively new technology enabling evaluation of vestibular function. The aim of this study was to compare the test results from two separate vHIT systems in a group of patients diagnosed with a unilateral vestibular schwannoma (VS) with regards to sensitivity, specificity and inter-examiner differences. METHODS: Forty-two patients were examined with two separate vHIT systems: EyeSeeCam® (system A) and ICS Impulse® (system B), by one of two examiners. All six semicircular canals (SCCs) were tested under standardized conditions, and strict criteria were set up for post-test interpretation. RESULTS: With the majority of test parameters, the two test systems were in agreement. Vestibular deficits were found in 40.5% (system A) to 45% (system B) of patients with a VS on the tested side; corresponding to a positive predictive value (PPV) of 86.4% (system B) to 94.4% (system A). The specificity was 97.6% for system A and 92.9% for system B. An overall agreement between the two vHIT systems measured as kappa was computed to be 0.61. There were no significant inter-examiner differences. When testing the vertical SCCs, a tendency of too high mean gain values was seen with system A but not with system B. CONCLUSION: In patients with unilateral VS, vHIT is a test with moderate sensitivity and high specificity in regard to identification of a vestibular deficit. There were no significant differences in test results between the two vHIT systems.

Associations of health literacy with socioeconomic position, health risk behavior, and health status: a large national population-based survey among Danish adults.

BACKGROUND: Health literacy concerns the ability of citizens to meet the complex demands of health in modern society. Data on the distribution of health literacy in general populations and how health literacy impacts health behavior and general health remains scarce. The present study aims to investigate the prevalence of health literacy levels and associations of health literacy with socioeconomic position, health risk behavior, and health status at a population level. METHODS: A nationwide cross-sectional survey linked to administrative registry data was applied to a randomly selected sample of 15,728 Danish individuals aged ≥25 years. By the short form HLS-EU-Q16 health literacy was measured for the domains of healthcare, disease prevention, and health promotion. Adjusted multinomial logistic regression analyses were used to estimate associations of health literacy with demographic and socioeconomic characteristics, health risk behavior (physical activity, smoking, alcohol consumption, body weight), and health status (sickness benefits, self-assessed health). RESULTS: Overall, 9007 (57.3%) individuals responded to the survey. Nearly 4 in 10 respondents faced difficulties in accessing, understanding, appraising, and applying health information. Notably, 8.18% presented with inadequate health literacy and 30.94% with problematic health literacy. Adjusted for potential confounders, regression analyses showed that males, younger individuals, immigrants, individuals with basic education or income below the national average, and individuals receiving social benefits had substantially higher odds of inadequate health literacy. Among health behavior factors (smoking, high alcohol consumption, and inactivity), only physical behavior [sedentary: OR: 2.31 (95% CI: 1.81; 2.95)] was associated with inadequate health literacy in the adjusted models. The long-term health risk indicator body-weight showed that individuals with obesity [OR: 1.78 (95% CI: 1.39; 2.28)] had significantly higher odds of lower health literacy scores. Poor self-assessed health [OR: 4.03 (95% CI: 3.26; 5.00)] and payments of sickness absence compensation benefits [OR: 1.74 (95% CI: 1.35; 2.23)] were associated with lower health literacy scores. CONCLUSIONS: Despite a relatively highly educated population, the prevalence of inadequate health literacy is high. Inadequate health literacy is strongly associated with a low socioeconomic position, poor health status, inactivity, and overweight, but to a lesser extent with health behavior factors such as smoking and high alcohol consumption.

Study on wideband tympanometry and absorbance within a Danish cohort of normal hearing adults.

PURPOSE: The objectives of this study was to present wideband tympanometry (WBT) data and absorbance with normal hearing and normal middle ear status. METHODS: Data were collected in 99 adult Caucasians with normal hearing and middle ear status. Energy absorbance was measured with an Interacoustics© Titan® using clicks for 1/24-octave frequency-intervals (0.226-8 kHz) with the ear canal air pressure alternated using a descending pressure sweep from + 250 to - 350 daPa. RESULTS: From the wideband energy absorbance tympanograms, the mean energy absorbance tympanogram, wideband averaged tympanogram and parameters such as ear canal volume, middle ear pressure and resonance frequency were determined. CONCLUSIONS: This study established a dataset containing descriptive analysis of wideband tympanograms and its derived parameters in Caucasian adults with normal hearing and normal middle ear conditions. The data presented in this study may serve as a future reference for WBT studies with Caucasian adults.

The relationship between serum potassium concentrations and electrocardiographic characteristics in 163,547 individuals from primary care.

AIMS: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels. METHODS AND RESULTS: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p < 0.0001); T-wave amplitude was 43.1 µV lower for each mmol/L decrease in potassium (p < 0.0001); and MCS was 0.13 higher per mmol/L decrease in potassium (p < 0.001). Moreover, P-wave duration and PR interval were prolonged by 2.7 and 4.6 ms for each mmol/L decrease in potassium (p < 0.0001), respectively. Within the lowest potassium range (2.0-4.1 mmol/L) P-wave amplitude was 3.5 µV higher for each mmol/L decrease in potassium (p < 0.0001). Within the high potassium range associations with the above-mentioned ECG parameters were much weaker.

Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography.

BACKGROUND: Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. METHODS: From 2010-2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors. RESULTS: In COGEN, adjusted odds ratios comparing the 2nd, 3rd and 4th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95-1.33), 1.35(95% CI 1.14-1.59) and 1.29(95% CI 1.09-1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3rd and 4th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04-1.71 and OR 1.36, 95% CI 1.06-1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36-2.30 and OR 1.65, 95% CI 1.26-2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia. CONCLUSION: Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD.

Intraoperative milrinone versus dobutamine in cardiac surgery patients: a retrospective cohort study on mortality.

BACKGROUND: Several choices of inotropic therapy are available and used in relation to cardiac surgery. Comparisons are necessary to select optimal therapy. In Denmark, dobutamine and milrinone are the two inotropic agents most commonly used to treat post-bypass low cardiac output syndrome. This study compares all-cause mortality with these drugs. METHODS: In a retrospective observational study we investigated 10,700 consecutive patients undergoing cardiac surgery from 1 April 2006 to 31 December 2013 at Aarhus and Aalborg University Hospitals in the Central and Northern Denmark Region. Prospectively entered data in the Western Danish Heart Registry on intraoperative use of inotropes were used to identify 952 patients treated with milrinone, 418 patients treated with dobutamine, and 82 patients receiving a combination of the two inotropes. All-cause mortality among patients receiving dobutamine was compared to all-cause mortality among milrinone receivers. Multiple logistic regression analyses including preoperative and intraoperative variables along with g-formula analyses were used to model 30-day and 1-year mortality risks. Reported were standardized mortality risk differences between the treatment groups. RESULTS: Among patients receiving intraoperative dobutamine, 18 (4.3%) died within 30 days and 49 (11.7%) within 1 year. Corresponding 30-day and 1-year mortality for milrinone receivers were 81 (8.5%) and 170 (17.9%). Risk of death within 30 days and 1 year was increased for intraoperative milrinone compared to dobutamine with a standardized risk difference of 4.06% (confidence interval (CI) 1.23; 6.89, p = 0.005) and 4.77% (CI 0.39; 9.15, p = 0.033), respectively. Sensitivity analyses including adjustment for milrinone preference, hemodynamic instability prior to cardiopulmonary bypass, and separate analyses on hospital level all confirmed a sign toward increased mortality among milrinone receivers. CONCLUSIONS: Intraoperative use of milrinone in cardiac surgery may be associated with an increase in all-cause mortality compared to use of dobutamine.

Venous Thromboembolic Complications to Hysterectomy for Benign Disease: A Nationwide Cohort Study.

STUDY OBJECTIVE: To estimate the risk of venous thromboembolic complications after abdominal, laparoscopic, and vaginal hysterectomy when performed for benign disorders. DESIGN: A nationwide cohort study (Canadian Task Force classification II-2). SETTING: Data from Danish national registers on all women undergoing hysterectomy for benign conditions from 1996 to 2015. PATIENTS: Women aged 18 years and older who underwent hysterectomy for benign disease were stratified into 3 groups according to the hysterectomy approach: abdominal, laparoscopic, or vaginal. INTERVENTIONS: Hysterectomy. MEASUREMENTS AND MAIN RESULTS: Eighty-nine thousand nine hundred thirty-one women met the inclusion criteria. Venous thromboembolism (VTE) as a diagnosis or cause of death was identified. The risk of postoperative VTE was examined with Cox proportional hazard models adjusting for age, surgical approach, and relevant comorbidities. The mean age was 49.9, 47.9, and 54.3 years for women with abdominal, laparoscopic, and vaginal hysterectomy, respectively. The crude incidences of VTE within 30 days after hysterectomy were 0.24% (n = 142), 0.13% (n = 12), and 0.10% (n = 21). The most important predictors of VTE were the approach to hysterectomy and a history of thromboembolic disease. In the multivariable analysis, the risk of VTE was significantly reduced with laparoscopic hysterectomy (hazard ratio [HR] = 0.51; 95% confidence interval [CI], 0.28-0.92; p = .03) and vaginal hysterectomy (HR = 0.39; 95% CI, 0.24-0.63; p < .001) when compared with the abdominal procedure. Data on postoperative heparin thromboprophylaxis were available in 53 566 patients, and the adjusted HR was 0.63 (95% CI, 0.42-0.96; p = .03) in patients receiving heparin thromboprophylaxis. CONCLUSION: The 30-day cumulative incidence of VTE after hysterectomy for benign conditions was low overall (0.19%). Laparoscopic hysterectomy and vaginal hysterectomy carry a lower risk than the abdominal procedure. Postoperative heparin thromboprophylaxis significantly reduces the risk of VTE and should be considered, especially if risk factors are present.

Storage time of intraoperative transfused allogeneic red blood cells is not associated with new-onset postoperative atrial fibrillation in cardiac surgery.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion has been associated with new-onset postoperative atrial fibrillation (POAF) following cardiac surgery. Prolonged storage time of RBC may increase the risk. The primary aim of the study was to evaluate whether the storage time of RBC is associated with development of POAF. MATERIALS AND METHODS: Pre-, per- and postoperative data were retrieved from the Western Denmark Heart Registry and local blood banks regarding patients who underwent coronary artery bypass surgery, valve surgery or combined procedures in Aalborg or Aarhus University Hospital during 2010-2014. Multiple logistic regression was used to determine the risk of POAF according to transfusion of RBC on the day of surgery. Furthermore, we determined trend in storage time of RBC according to risk of POAF using restricted cubic splines. Patients with a history of preoperative atrial fibrillation, patients who received transfusions preoperative and patients who died at the day of surgery were among excluded patients. RESULTS: A total of 2,978 patients with a mean age of 66.4 years were included and 609 patients (21%) received RBC transfusion on the day of surgery. POAF developed in 752 patients (25%) and transfused patients were at an increased risk compared with non-transfused patients (adjusted Odds Ratios for patients receiving RBC: 1.37; 95% CI: 1.11-1.69, P-value = 0.004). However, RBC transfusion was not necessarily the cause of POAF and may only be a marker for development of POAF. There was no significant association between storage time of RBC and POAF. CONCLUSIONS: In contrast to intraoperative allogeneic RBC transfusion in general, increased storage time of RBC is not associated with development of POAF in cardiac surgery.