BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.
Background Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus. Aim To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Methods The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause. Results 25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment. Conclusions Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI. Funding Acknowledgement Type of funding source: None
Worsening of TI after PPI was not rare and was observed more often in older patients, with abnormal LV relaxation and who developed pulmonary hypertension after the procedure.
In the period 1988-1993, 241 patients had Klebsiella bacteraemia at our medical centre. The annual number of patients with positive blood cultures increased from 306 in 1988 to 622 in 1993, representing a 4.5-6% positivity rate of drawn cultures. After E. coli, Klebsiella was the leading cause of Gram-negative bacteraemia. During this period, the absolute number of Klebsiella bacteraemia increased from 25 in 1988 to 84 in 1993; this represents a true increase in Klebsiellaa bacteraemia, from 6-7% of positive cultures in the late 1980s to 12-13% in more recent years. There were 210 cases with K. pneumoniae and 31 with K. oxytoca. A representative sample of 80 records was retrieved and subdivided into two groups: community-acquired Klebsiella bacteraemia (CAKB) vs. hospital-acquired Klebsiella bacteraemia (HAKB). Urinary tract infection was the underlying source of 58% of CAKB vs 28% of HAKB (p < 0.01); pneumonia occurred significantly more often in HAKB (25%) than in CAKB (7%) (p < 0.01). In HAKB, as compared to CAKB, serious manifestations of illness were more common, e.g. shock (65% vs. 37%, p < 0.046) and respiratory failure (45% vs. 20%, p < 0.046). Overall mortality was 32%, 22% of patients with CAKB died vs. 42% of those with HAKB (p < 0.05). Multiple drug resistance was very common: only 57% of all Klebsiella strains were susceptible to gentamicin, 66% to ceftriaxone, 70% to ciprofloxacin, and 83% to amikacin. The susceptibility rates of Klebsiella spp isolated from patients with HAKB were significantly lower (p < 0.001). Sepsis due to multiple-drug-resistant Klebsiellaa has become frequent, carrying significant morbidity and mortality. Restriction of broad-spectrum antimicrobials in the hospital and the community as well as implementation of infection control measures are needed to contain this problem.
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