Veli-Pekka Harjola - Academia.edu (original) (raw)

Papers by Veli-Pekka Harjola

European heart journal, 2007

Cystatin C, a novel marker of renal function, has been implicated as a prognostic marker in cardi... more Cystatin C, a novel marker of renal function, has been implicated as a prognostic marker in cardiovascular disease. We investigated the prognostic value of cystatin C in acute heart failure (AHF) in comparison to other markers of renal function and NT-proBNP. Patients with cystatin C measurements (n = 480) from a prospective multicentre study on AHF were included. All-cause mortality at 12 months was 25.4%. Cystatin C, creatinine, age, gender, and systolic blood pressure on admission were identified as independent prognostic risk factors. Cystatin C above median (1.30 mg/L) was associated with the highest adjusted hazard ratio, 3.2 (95% CI 2.0-5.3), P < 0.0001. Mortality increased significantly with each tertile of cystatin C. Combining tertiles of NT-proBNP and cystatin C improved risk stratification further. Moreover, in patients with normal plasma creatinine, elevated cystatin C was associated with significantly higher mortality at 12 months: 40.4% vs. 12.6% in patients with b...

Normal concentrations of D-Dimer can be used to exclude venous thromboembolism (VTE). However, me... more Normal concentrations of D-Dimer can be used to exclude venous thromboembolism (VTE). However, methods for sensitive and quantitative D-Dimer measurements at the point-of-care (POC) are still limited. We developed a 10-min, non-competitive immunofluorometric assay for D-Dimer in citrated whole blood and plasma using pre-dispensed reagents dried in single assay wells. The simple, automated assay procedure comprises a 1:50 sample dilution, one-step incubation, washing, and time-resolved fluorometric measurement directly from the wet well surface. The limits of detection (background + 3SD) and quantification (CV &amp;amp;amp;amp;amp;amp;amp;lt;15%) were 0.05 and 0.2 mg/L D-Dimer, respectively, and the assay was linear up to 400 mg/L. Correlations to Roche TinaQuant (r=0.726, n=200) and Biopool Auto.Dimer (r=0.190, n=149) were carried out using citrated plasma. Diagnostic sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values were 98.7%, 64.4%, 99.1% and 55.1%, and 92.2%, 81.0%, 95.9% and 68.3%, respectively, using cut-off values of 0.6 and 1.0 mg/L, respectively, in outpatients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) (n=77) compared with outpatients with various other diseases (n=174). The within- and between-run CVs near the cut-off values were &amp;amp;amp;amp;amp;amp;amp;lt; or =10% in both whole blood and plasma. The 95th percentile upper range in apparently healthy individuals was 0.68 mg/L of whole blood (n=101). The high sensitivity and NPV suggest that the rapid immunofluorometric assay could be valuable for rapid exclusion of VTE in outpatients. With appropriate cut-offs, the assay could potentially be used as a stand-alone test or combined with clinical probability assessment, but further studies are required.

terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor al... more terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), epinephrine and norepinephrine were determined. The severity of heart failure was assessed by peak oxygen consumption (VO 2 max) during exercise. Results: Plasma apelin levels were similar in IDC patients and in control subjects (26.5 vs. 24.1 pg/mL, P = NS). Unlike the levels of NT-proBNP, IL-6, TNF-α, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure (P = NS). Conclusions: Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction caused by idiopathic dilated cardiomyopathy. On the other hand, our results confirm the utility of NT-proBNP, IL-6, and TNF-α as powerful indicators of the severity of cardiac dysfunction.

with insulin and glucose exerts beneficial effects on myocardial function, whereas free fatty aci... more with insulin and glucose exerts beneficial effects on myocardial function, whereas free fatty acids (FFA) may compromise contractile function. It is unknown whether short-term modulation of myocardial substrate supply affects risk markers of HF severity. Methods: We studied 8 patients with ischemic heart disease and chronic HF and 8 healthy controls. Each patient was subjected to a 3-h infusion of 1) saline (SAL), 2) insulin-glucose (INS) (high insulin, low FFA), and 3) somatostatin-heparin (HEP) (low insulin, high FFA). Measurements were made at baseline and during the last 15 min of each study period. Results: Hemodynamics remained unaltered. NT-proBNP, OPG and ADI were increased in patients compared to controls [NT-proBNP (pg/ml): 169 ± 46 (patients) vs. 8 ± 2 (controls), p b 0.01]; [OPG (ng/ml): 1.8± 0.3 (patients) vs. 1.2 ± 0.1 (controls), p b 0.05]; [ADI (mg/L): 13.7± 2.1 (patients) vs. 10.0 ± 1.4 (controls), p = 0.07]. Expressed as percentage change from fasting baseline values, INS caused a significant decrease in NT-proBNP [(%): 98 ± 5 (SAL); 90± 3 (INS); 103± 4 (HEP), p b 0.05] and a near significant decrease in ADI [(%): 97± 1 (SAL); 94± 1 (INS); 97 ± 1 (HEP), p = 0.096]. OPG tended to be decreased during INS [(%): 119± 12 (SAL); 97 ± 5 (INS); 111 ± 11 (HEP), p = 0.25]. Conclusions:

Methods: Patients with frequent migraine with aura, refractory to at least two prophylactic medic... more Methods: Patients with frequent migraine with aura, refractory to at least two prophylactic medications, were recruited. Transthoracic contrast echocardiography was used to detect right-to-left shunts and semi-quantitatively assess their size. Patients with large or medium size PFO were randomised to PFO closure with STARFlex® or a sham procedure. Patients and headache specialists were blind to randomisation during an initial 180-day follow-up. Results: 432 patients were recruited and screened. 260 (60.2%) had a shunt, of which 163 (37.7% of total and 62.7% of those with shunts) had a large PFO. The mean PFO diameter was 9.21 mm (±3.27 mm). 73 patients were randomised to the sham procedure and 74 to closure with STARFlex®. Preliminary results (March 2006) demonstrated that 42% of closure arm had a 50% reduction in migraine headache days compared to 23% in the control arm. Full data from the initial follow-up period will be available for presentation at the XXI Nordic Congress of Cardiology. Conclusions: Large right-to-left shunts (mostly PFOs) are 6 times more common in migraine with aura patients than in the general population. The average PFO diameter in these patients is similar to that seen in patients with paradoxical embolism. Preliminary results from MIST I have successfully demonstrated that closure of PFO with STARFlex® provides a significant treatment effect in some patients.

Levosimendan, a new calcium sensitizer, was administered orally to 10 patients with severe conges... more Levosimendan, a new calcium sensitizer, was administered orally to 10 patients with severe congestive heart failure (CHF), who had a mean baseline pulmonary capillary wedge pressure (PCWP) of 22 mm Hg and a left ventricular ejection fraction of 23%. Each patient received 3 escalating doses of 1 mg, 2 mg, and 4 mg of levosimendan within 18–24 hours in an

Clinical chemistry, 2015

Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complement... more Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the conce...

Journal of the American College of Cardiology, Jan 14, 2014

Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes w... more Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients no...

Scandinavian Cardiovascular Journal, 2011

Oral levosimendan improves ventricular function in short-term clinical trials. The effects of lon... more Oral levosimendan improves ventricular function in short-term clinical trials. The effects of long-term treatment with oral levosimendan were investigated on echocardiographic parameters of left ventricular function in patients with chronic heart failure. Twenty-nine patients with NYHA III-IV congestive chronic HF were prospectively enrolled in a randomised, double-blind, placebo controlled study. Oral levosimendan was administered on top of existing medication over a treatment period of at least 180 days. Echocardiographic measurements estimating pulmonary capillary wedge pressure (PCWP) and tissue Doppler mitral basal myocardial velocities (Sm, Em) were performed at baseline and 90 and 180 days after randomisation. Estimated PCWP at baseline was elevated in both groups and decreased by 13% in the levosimendan group compared to an increase of 9% in the placebo group (p = 0.035). Sm was decreased in both groups at baseline and improved by 0.9 cm/s in the levosimendan group and decreased by 0.1 cm/s in the placebo group (p = 0.035). Levosimendan did not significantly alter heart rate or systolic blood pressure. Oral levosimendan improved hemodynamic function in chronic heart failure patients and the effect was sustained over the 180-day follow-up period.

Journal of the American College of Cardiology, 2014

This study sought to define the relationship between body mass index (BMI) and mortality in heart... more This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. Normal-weight patients (BMI 18.5 to 25 kg/m(2)) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m(2); p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Notably, the…

International Journal of Cardiology, 2012

Aims: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and ... more Aims: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart failure. Methods: Patients with AHF (n = 620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined. Results: The overall mortality was 60.3% (n = 374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p b 0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12 months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4-2.2; p b 0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome. Conclusion: The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF.

Clinical Physiology and Functional Imaging, 2011

Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (D... more Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (DL,CO), but data on the mechanisms involved are inconsistent. We wanted to investigate whether reduction in diffusing capacity of alveolocapillary membrane (DM) and pulmonary capillary blood volume (Vc) is associated with the extent of PE or the presence and severity of right ventricular dysfunction (RVD) induced by PE and how the possible changes are corrected after 7-month follow-up. Forty-seven patients with acute non-massive PE in spiral computed tomography (CT) were included. The extent of PE was assessed by scoring mass of embolism. DL,CO, Vc, DM and alveolar volume (VA) were measured by using a single breath method with carbon monoxide and oxygen both at the acute phase and 7 months later. RVD was evaluated with transthoracic echocardiography and electrocardiogram. Fifteen healthy subjects were included as controls. DL,CO, DL, CO ⁄ VA, DM, vital capacity (VC) and VA were significantly lower in the patients with acute PE than in healthy controls (P<0AE001). DM ⁄ Vc relation was significantly lower in patients with RVD than in healthy controls (P = 0AE004). DM correlated inversely with central mass of embolism (r = )0AE312; P = 0AE047) whereas Vc did not. DM, DL,CO, VC and VA improved significantly within 7 months. In all patients (P = 0AE001, P = 0AE001) and persistent RVD (P = 0AE020, P = 0AE012), DM and DL,CO remained significantly lower than in healthy controls in the follow-up. DM was inversely related to central mass of embolism. Reduction in DM mainly explains the sustained decrease in DL,CO in PE after 7 months despite modern treatment of PE.

Clinical Pharmacokinetics, 2007

Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It ... more Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. It increases myocardial contractility, reduces the filling pressure and dilates both the peripheral and coronary vessels. The circulating metabolites of levosimendan, OR-1855 and OR-1896, are formed and eliminated slowly after intravenous administration of levosimendan. The aim of this study was to investigate the effect of impaired renal function and haemodialysis on the pharmacokinetics of levosimendan, OR-1855 and OR-1896. This study was an open-label, nonrandomised, phase I pharmacokinetic study. Levosimendan was administered as a single-dose infusion of 0.1 microg/kg/minute for 24 hours. The follow-up period lasted 3 weeks. Twenty-fivepatients were included:12 patients with severe chronic renal failure (CRF) with creatinine clearance of &amp;amp;amp;amp;amp;amp;amp;lt; 30 mL/minute/1.73 m(2) and 13 patients with end-stage renal disease (ESRD) undergoing haemodialysis. A group of 12 healthy subjects served as controls. Levosimendan, the parent drug, was eliminated rapidly from the plasma after discontinuation of its infusion, with an elimination half-life (t(1/2)) [mean +/- standard error of mean] of 1.5 +/- 0.09 hours in ESRD patients undergoing haemodialysis, 1.0 +/- 0.2 hours in patients with severe CRF and 0.91 +/- 0.03 hours in healthy subjects. The t(1/2) of levosimendan was significantly longer (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in ESRD patients undergoing haemodialysis than in healthy subjects. The t(1/2) of OR-1855 and OR-1896 were 94.0 +/- 20.4 hours and 96.5 +/- 19.5 hours, respectively, in ESRD patients undergoing haemodialysis compared with 60.8 +/- 5.2 and 61.6 +/- 5.2 hours, respectively, in healthy subjects (p = not significant). The t(1/2) of OR-1855 was significantly longer (85.0 +/- 13.6 hours) in patients with severe CRF than in healthy subjects (60.8 +/- 5.2 hours, p &amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (C(max)) of the metabolites were approximately 2-fold in patients with ESRD undergoing haemodialysis and patients with severe CRF compared with healthy subjects. The mean unbound fraction (f(u)) of levosimendan in plasma was approximately 2% in each study group, whereas the f(u) of the metabolites was considerably higher (63-70%). In contrast to levosimendan, the metabolites were dialysable, with dialysis clearance of approximately 100 mL/minute. The haemodynamic responses and adverse event profiles were similar in the study groups, with headache, palpitations and dizziness being the most frequently recorded adverse events. The t(1/2) of the levosimendan metabolites was prolonged 1.5-fold and their AUC and C(max) were 2-fold in patients with severe CRF and ESRD patients undergoing haemodialysis as compared with healthy subjects. These results suggest that the dose should be reduced when levosimendan is used for the treatment of congestive heart failure in patients with severe renal insufficiency.

Cardiovascular Drugs and Therapy, 2013

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as... more Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure.

Biomarkers, 2013

Cardiorenal biomarkers (CBs) predict outcome in acute heart failure (AHF). To evaluate CBs in ear... more Cardiorenal biomarkers (CBs) predict outcome in acute heart failure (AHF). To evaluate CBs in early follow-up prognostication. In 124 AHF patients, levels of CystatinC, NT-proBNP and TroponinI measured five weeks from admission (W5) and relative change from day 2 (D2) were assessed for 6-month prognosis (mortality/HF hospitalization). The combined end-point occurred in 33 patients (27%). D2-, W5-cystatin≥ median, and lack of ≥30%decrease in NT-proBNP were independent predictors of outcome. Additionally, a risk score established from W5 CBs identified patients with very high event rate. CBs at early follow-up of AHF may guide risk stratification.

Background Vitamin K antagonists are highly effective in preventing stroke in patients with atria... more Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.

Academic Emergency Medicine, 2011

The maturation of emergency medicine (EM) as a specialty has coincided with dramatic increases in... more The maturation of emergency medicine (EM) as a specialty has coincided with dramatic increases in emergency department (ED) visit rates, both in the United States and around the world. ED crowding has become a public health problem where periodic supply and demand mismatches in ED and hospital resources cause long waiting times and delays in critical treatments. ED crowding has been associated with several negative clinical outcomes, including higher complication rates and mortality. This article describes emergency care systems and the extent of crowding across 15 countries outside of the United and the United Kingdom. The authors are local emergency care leaders with knowledge of emergency care in their particular countries. Where available, data are provided about visit patterns in each country; however, for many of these countries, no national data are available on ED visits rates or crowding. For most of the countries included, there is both objective evidence of increases in ED visit rates and ED crowding and also subjective assessments of trends toward higher crowding in the ED. ED crowding appears to be worsening in many countries despite the presence of universal health coverage. Scandinavian countries with robust systems to manage acute care outside the ED do not report crowding is a major problem. The main cause for crowding identified by many authors is the boarding of admitted patients, similar to the United States. Many hospitals in these countries have implemented operational interventions to mitigate crowding in the ED, and some countries have imposed strict limits on ED length of stay (LOS), while others have no clear