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1.

Background

The effectiveness of rivaroxaban to reduce post-thrombotic syndrome in patients with venous thromboembolism is largely unknown. We compared rates of post-thrombotic syndrome in patients given rivaroxaban versus warfarin in a cohort of patients with incident venous thromboembolism receiving routine clinical care.

Methods

We linked Danish nationwide registries to identify all patients with incident venous thromboembolism who were new users of rivaroxaban or warfarin and compared rates of post-thrombotic syndrome using an inverse probability of treatment-weighting approach to account for baseline confounding.

Results

We identified 19,957 oral anticoagulation–naive patients with incident venous thromboembolism treated with warfarin or rivaroxaban (mean age, 64 years; 48% were female, 45.5% had pulmonary embolism). The propensity-weighted rate of post-thrombotic syndrome at 3 years follow-up was 0.53 incidents per 100 person-years with rivaroxaban versus 0.55 per 100 person-years with warfarin, yielding a hazard rate of 0.88 (95% confidence interval, 0.66-1.17). This association remained consistent across types of venous thromboembolism (deep venous thrombosis vs pulmonary embolism, and provoked vs unprovoked venous thromboembolism) and when censoring patients with recurrent venous thromboembolism.

Conclusions

In this clinical practice setting, rivaroxaban was associated with lower but statistically nonsignificant rates of post-thrombotic syndrome, which did not appear to be mediated only by an effect on recurrent venous thromboembolism.  相似文献   

2.

Background

Low-molecular-weight heparin (LMWH) is the treatment of choice in cancer patients with venous thromboembolism. However, data on continuing LMWH treatment beyond 6 months remain scanty.

Methods

We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate of venous thromboembolism recurrences and major bleeding appearing beyond the first 6 months of anticoagulant therapy in cancer patients with venous thromboembolism, according to therapy with LMWH or vitamin K antagonists (VKA). We performed a propensity score-matched cohort study.

Results

After propensity matching, 482 cancer patients continued to receive LMWH and 482 switched to VKA. During the course of anticoagulant therapy (mean 275.5 days), 57 patients developed venous thrombosis recurrences (recurrent pulmonary embolism 26, recurrent deep vein thrombosis 29, both 2), 28 had major bleeding, 38 had nonmajor bleeding, and 129 died. No patient died of recurrent venous thrombosis, and 5 patients died of bleeding (2 were on LMWH, 3 on VKA). Patients who continued with LMWH had a similar rate of deep vein thrombosis recurrences (relative risk [RR] 1.41; 95% confidence interval [CI], 0.68-2.93), pulmonary embolism recurrences (RR 0.73; 95% CI, 0.34-1.58), major bleeding (RR 0.96; 95% CI, 0.51-1.79), or nonmajor bleeding (RR 1.15; 95% CI, 0.55-2.40), compared with those who switched to VKA, but a higher mortality rate (RR 1.58; 95% CI, 1.13-2.20).

Conclusions

In cancer patients with venous thromboembolism who completed 6 months of LMWH therapy, switching to VKA was associated with a similar risk of venous thrombosis recurrences or bleeding when compared with patients who continued LMWH.  相似文献   

3.

Background

Direct-acting oral anticoagulants (DOACs), which have gained approval for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism, have become increasingly preferred over warfarin given their predictable pharmacodynamics, lack of required monitoring, and superior outcomes. Direct-acting oral anticoagulants have been shown to be associated with an increased frequency of gastrointestinal bleeding compared with warfarin, but the severity and characteristics of gastrointestinal bleeding in these patients is poorly understood.

Methods

We retrospectively evaluated electronic medical records of patients with gastrointestinal bleeding (n = 8496) from 2010-2016. We identified 61 patients with gastrointestinal bleeding episodes while treated with DOACs (rivaroxaban, dabigatran, or apixaban) and 123 patients with gastrointestinal bleeding while taking warfarin. We randomly selected a control group of 296 patients with gastrointestinal bleeding who were not receiving anticoagulation treatment from the same sample. Outcomes included the need for hospitalization, blood transfusion, endoscopic or surgical intervention, and 30-day mortality.

Results

The DOAC and warfarin groups were similar in terms of age and underlying comorbidity (assessed using the Charlson Comorbidity Index), but the DOAC group had greater concomitant aspirin use. Gastrointestinal bleeding was classified as upper (n = 186), lower (n = 88), anorectal (n = 183), small bowel (n = 9), and indeterminate (n = 14). After adjusting for differences in baseline variables, the DOAC group had fewer hospitalizations and required fewer transfusions than the warfarin group. The DOAC and control groups were not statistically different for all outcomes. There were no significant mortality differences among groups.

Conclusion

Although prior studies have shown a higher frequency of gastrointestinal bleeding in patients treated with DOACs compared with warfarin, our data suggest that gastrointestinal bleeding in patients taking DOACs may be less severe. These differences occurred despite significantly greater concomitant aspirin use in the DOAC group compared with warfarin users.  相似文献   

4.

Background

Little is known about predictors and outcomes of recurrent venous thromboembolism in elderly patients.

Methods

We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was symptomatic recurrent venous thromboembolism. We explored the association between baseline characteristics and treatments and recurrent venous thromboembolism using competing risk regression, adjusting for periods of anticoagulation as a time-varying covariate. We also assessed the clinical consequences (case-fatality, localization) of recurrent venous thromboembolism.

Results

During a median follow-up period of 30 months, 122 patients developed recurrent venous thromboembolism, corresponding to a 3-year cumulative incidence of 14.8%. The case-fatality of recurrence was high (20.5%), particularly in patients with unprovoked (23%) and cancer-related venous thromboembolism (29%). After adjustment, only unprovoked venous thromboembolism (sub-hazard ratio, 1.67 compared with provoked venous thromboembolism; 95% confidence interval, 1.00-2.77) and proximal deep vein thrombosis (sub-hazard ratio, 2.41 compared with isolated distal deep vein thrombosis; 95% confidence interval, 1.07-5.38) were significantly associated with recurrence. Patients with initial pulmonary embolism were more likely to have another pulmonary embolism as a recurrent event than patients with deep vein thrombosis.

Conclusions

Elderly patients with acute venous thromboembolism have a substantial long-term risk of recurrent venous thromboembolism, and recurrence carries a high case-fatality rate. Only 2 factors, unprovoked venous thromboembolism and proximal deep vein thrombosis, were independently associated with recurrent venous thromboembolism, indicating that traditional risk factors for venous thromboembolism recurrence (eg, cancer) may be less relevant in the elderly.  相似文献   

5.

Background

The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors.

Methods

By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum.

Results

A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism.

Conclusions

Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.  相似文献   

6.

Background

Catheter exchange over a guidewire is frequently performed for malfunctioning peripherally inserted central catheters (PICCs). Whether such exchanges are associated with venous thromboembolism is not known.

Methods

We performed a retrospective cohort study to assess the association between PICC exchange and risk of thromboembolism. Adult hospitalized patients that received a PICC during clinical care at one of 51 hospitals participating in the Michigan Hospital Medicine Safety consortium were included. The primary outcome was hazard of symptomatic venous thromboembolism (radiographically confirmed upper-extremity deep vein thrombosis and pulmonary embolism) in those that underwent PICC exchange vs those that did not.

Results

Of 23,010 patients that underwent PICC insertion in the study, 589 patients (2.6%) experienced a PICC exchange. Almost half of all exchanges were performed for catheter dislodgement or occlusion. A total of 480 patients (2.1%) experienced PICC-associated deep vein thrombosis. The incidence of deep vein thrombosis was greater in those that underwent PICC exchange vs those that did not (3.6% vs 2.0%, P < .001). Median time to thrombosis was shorter among those that underwent exchange vs those that did not (5 vs 11 days, P = .02). Following adjustment, PICC exchange was independently associated with twofold greater risk of thrombosis (hazard ratio [HR] 1.98; 95% confidence interval [CI], 1.37-2.85) vs no exchange. The effect size of PICC exchange on thrombosis was second in magnitude to device lumens (HR 2.06; 95% CI, 1.59-2.66 and HR 2.31; 95% CI, 1.6-3.33 for double- and triple-lumen devices, respectively).

Conclusion

Guidewire exchange of PICCs may be associated with increased risk of thrombosis. As some exchanges may be preventable, consideration of risks and benefits of exchanges in clinical practice is needed.  相似文献   

7.

Background

Cancer is associated with a prothrombotic state and increases the risk of thrombotic events in patients with atrial fibrillation. We described the clinical characteristics and outcomes and assessed the safety and efficacy of apixaban versus warfarin in patients with atrial fibrillation and cancer in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Methods

The association between cancer and clinical outcomes was assessed using Cox regression models. At baseline, 1236 patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had remote cancer.

Results

There were no significant associations between history of cancer and stroke/systemic embolism, major bleeding, or death. The effect of apixaban versus warfarin for the prevention of stroke/systemic embolism was consistent among patients with a history of cancer (event/100 patient-years = 1.4 vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The safety and efficacy of apixaban versus warfarin were preserved among patients with and without active cancer. Apixaban was associated with a greater benefit for the composite of stroke/systemic embolism, myocardial infarction, and death in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86; 95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10) (interaction P = .0028).

Conclusions

Cancer was not associated with a higher risk of stroke. The superior efficacy and safety of apixaban versus warfarin were consistent in patients with and without cancer. Our positive findings regarding apixaban use in patients with atrial fibrillation and cancer are exploratory and promising, but warrant further evaluation.  相似文献   

8.

Background

Anemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism and whether the presence of anemia can refine risk assessment for prediction of venous thromboembolism, thereby adding incremental utility to a validated model.

Methods

In the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban trial (APEX), 7513 hospitalized medical patients were randomized to receive either betrixaban or standard-of-care enoxaparin for thromboprophylaxis. Baseline hemoglobin concentrations were obtained in 6861 patients, with a follow-up of 77 days. Symptomatic venous thromboembolism events, including symptomatic deep vein thrombosis, pulmonary embolism, and venous thromboembolism–related mortality, were compared between low-hemoglobin and normal-hemoglobin groups (normal range: 12.5-17.0 g/dL for males and 11.0-15.5 g/dL for females). The relationship between anemia and venous thromboembolism events was assessed by fitting a univariable and multivariable logistic regression model composed of thromboprophylaxis and risk factors. Venous thromboembolism risk refinement by hemoglobin measurement was evaluated in the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) risk assessment model.

Results

Low hemoglobin at baseline was associated with a greater risk of symptomatic venous thromboembolism (relative risk [RR] 1.94 [95% confidence interval, 1.27-2.98]; P = .002), symptomatic deep vein thrombosis (RR 2.29 [1.12-4.68]; P = .019), and nonfatal pulmonary embolism (RR 2.63 [1.22-5.65]; P = .010) but not venous thromboembolism–related mortality (RR 1.47 [0.71-3.04]; P = .30). After adjusting for thromboprophylaxis, history of previous venous thromboembolism, intensive or coronary unit admission, and D-dimer, low hemoglobin (as a categorical or continuous variable) remained associated with an increased likelihood of venous thromboembolism (adjusted odds ratio 1.71 [95% confidence interval, 1.09-2.69]; P = .020). Low hemoglobin also improved risk discrimination and reclassification after inclusion in the IMPROVE model.

Conclusions

Anemia was independently associated with a greater risk of symptomatic venous thromboembolism among acutely ill medical patients despite the provision of thromboprophylaxis. Hemoglobin measurement also improved risk stratification by the IMPROVE venous thromboembolism risk score.  相似文献   

9.

Background

Frailty and acute kidney injury are independently associated with an increased risk of morbidity and mortality. The degree of frailty can be assessed by the Clinical Frailty Score (CFS). This study assessed whether an individual's CFS was associated with acute kidney injury in acute elderly medical admissions and recorded the short-term outcomes.

Methods

This was a single-center prospective observational cohort study. All patients aged ≥65 years admitted under an acute medical take over 12 nonconsecutive days were included. Patient demographics, comorbidities, baseline CFS, and renal status on admission were recorded. Outcomes of death, length of stay, and hospital re-attendance were assessed 2 weeks following admission.

Results

Of 164 patients (77 males), 19% had acute kidney injury on admission and 22% were considered severely frail. Severe frailty was associated with acute kidney injury (P = .01) and death within 2 weeks (P = .01). Two-week mortality was highest among patients with both (36%).

Conclusion

The incidence of acute kidney injury in “severely frail” acutely unwell elderly patients is significantly higher and associated with an increased short-term mortality. The CFS may be useful in acute illness to guide clinical decisions in elderly patients.  相似文献   

10.

Purpose

We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population.

Methods

Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling–753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding.

Results

When compared with patients without a history of falling, patients with a history of falling were older, more likely to be female and to have dementia, cerebrovascular disease, depression, diabetes, heart failure, osteoporosis, fractures, and higher CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P < .0001), but similar rates of stroke or systemic embolism and hemorrhagic stroke. There was no evidence of a differential effect of apixaban compared with warfarin on any outcome, regardless of history of falling. Among those with a history of falling, subdural bleeding occurred in 5 of 367 patients treated with warfarin and 0 of 386 treated with apixaban.

Conclusions

Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling.  相似文献   

11.

Background

We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following a provoked venous thromboembolism.

Methods

Using US MarketScan claims from November 2012 to March 2017, we identified adults with ≥1 primary hospitalization or emergency department diagnosis code for venous thromboembolism, a provoking (major or minor, persistent or transient) risk factor, at least 3 months of continuous rivaroxaban treatment, and ≥12 months of continuous insurance benefits prior to their qualifying venous thromboembolism. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or nonaspirin antiplatelet agents but may have received aspirin) after the initial 3 months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Twelve month incidences of recurrent venous thromboembolism or major bleeding were compared between cohorts using Cox regression (according to an intention-to-treat methodology) and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Among patients experiencing a provoked venous thromboembolism and treated with rivaroxaban for the first 3 months (N=4,990), continued rivaroxaban use beyond 3 months (median [25%, 75% range duration of additional rivaroxaban use?=?3 [2, 5] months) was associated with a 44% (95% CI of 9%-66%) lower hazard of recurrent venous thromboembolism without altering major bleeding risk [HR of 0.87, 95% CI of 0.51-1.49] versus anticoagulation discontinuation (with or without aspirin use).

Conclusions

Our study suggests continuing rivaroxaban after the initial 3 month period was associated with a decreased risk of recurrent venous thromboembolism. The observed reduction in recurrent venous thromboembolism with prolonged rivaroxaban use was not associated with a significant change in major bleeding risk.  相似文献   

12.

Background

Sedation of mechanically ventilated patients should optimize comfort and safety while avoiding over-sedation and adverse outcomes. To our knowledge, characteristics associated with attaining target sedation are unknown.

Objectives

Evaluate current sedation practice at a single center and explore which patient characteristics are associated with attaining target sedation.

Methods

This is a single-center, retrospective chart review of sedated, ventilated patients in a medical/surgical ICU. Demographic and clinical data were collected. Univariate and multivariate logistic regression analyses were used with attaining target sedation as the dependent variable.

Results

Of the 100 patients included (median 60.5 years), 50 attained target sedation. Univariate analyses (a = 0.10) revealed factors associated with target sedation were age (P = 0.08), history of alcohol abuse (P = 0.08), multiple comorbidities (P = 0.09), and delirium monitoring (P = 0.002). Multivariate analysis revealed an association between delirium monitoring/documentation and attaining target sedation (P = 0.005; OR 9.2; 95% CI 2.3–36.8).

Conclusions

Patients without appropriate delirium monitoring/documentation had significantly reduced likelihood of achieving target sedation.  相似文献   

13.
14.

Background

Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored.

Methods

We used the Registro Informatizado de Enfermedad TromboEmbólica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers.

Results

Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carriers had a similar rate of venous thromboembolism recurrence (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.82-1.64), half the rate of major bleeding (adjusted HR, 0.50; 95% CI, 0.25-0.99) and a nonsignificantly lower rate of nonmajor bleeding (adjusted HR, 0.66; 95% CI, 0.43-1.01) than noncarriers. Prothrombin mutation carriers and noncarriers had a comparable rate of venous thromboembolism recurrence (adjusted HR, 1.00; 95% CI, 0.68-1.48), major bleeding (adjusted HR, 0.75; 95% CI, 0.42-1.34), and nonmajor bleeding events (adjusted HR, 1.10; 95% CI, 0.77-1.57).

Conclusions

During the anticoagulation course, factor V Leiden carriers had a similar risk for venous thromboembolism recurrence and half the risk for major bleeding compared with noncarriers. This finding may contribute to decision-making regarding anticoagulation duration in selected factor V Leiden carriers with venous thromboembolism.  相似文献   

15.

Background

Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined.

Methods

The current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism).

Results

During the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n?=?27) was similar to that related to pulmonary embolism recurrences (n?=?26).

Conclusions

In this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting.  相似文献   

16.

Background

The mechanisms contributing to the success of cardiac rehabilitation (CR) are poorly understood and may include assessment, monitoring and review activities enabled by continuity of care and this is investigated in this study.

Objectives

To identify active assessment components of CR.

Methods

A qualitative study using focus groups and individual interviews. CR staff (n = 39) were recruited via professional association email and network contacts and organised into major themes.

Results

CR staff assessment strategies and timely actions undertaken provided a sophisticated post-discharge safety net for patients. Continuity of care enabled detection of adverse health indicators, of which medication issues were prominent. Interventions were timely and personalised and therefore likely to impact outcomes, but seldom documented or reported and thus invisible to audit.

Conclusion

CR staff assessment and intervention activities provide an unrecognised safety net of activities enabled by continuity of care, potentially contributing to the effectiveness of CR.  相似文献   

17.

Objective

Combining a macrolide or a fluoroquinolone to beta-lactam regimens in the treatment of patients with moderate to severe community-acquired pneumonia is recommended by the international guidelines. However, the information in patients with bacteraemic pneumococcal pneumonia is limited.

Methods

A propensity score technique was used to analyze prospectively collected data from all patients with bacteraemic pneumococcal pneumonia admitted from 2000 to 2015 in our institution, who had received empirical treatment with third-generation cephalosporin in monotherapy or plus macrolide or fluoroquinolone.

Results

We included 69 patients in the monotherapy group and 314 in the combination group. After adjustment by PS for receiving monotherapy, 30-day mortality (OR 2.89; 95% CI 1.07–7.84) was significantly higher in monotherapy group. A higher 30-day mortality was observed in monotherapy group in both 1:1 and 1:2 matched samples although it was statistically significant only in 1:2 sample (OR: 3.50 (95% CI 1.03–11.96), P = 0.046).

Conclusions

Our study suggests that in bacteraemic pneumococcal pneumonia, empirical therapy with a third-generation cephalosporin plus a macrolide or a fluoroquinolone is associated with a lower mortality rate than beta-lactams in monotherapy. These results support the recommendation of combination therapy in patients requiring admission with moderate to severe disease.  相似文献   

18.

Background

Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug–drug interaction by the concomitant use of DOACs and amiodarone.

Methods

We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I2) < 25%.

Results

Four trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone.

Conclusion

On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.  相似文献   

19.

Background

The value of genetic thrombophilia testing in elderly patients with an unprovoked venous thromboembolism is unclear. We assessed whether the Factor V Leiden and the prothrombin G20210A mutation are associated with recurrent venous thromboembolism in elderly patients in a prospective multicenter cohort study.

Methods

We genotyped the Factor V Leiden and the prothrombin G20210A mutation in 354 consecutive in- and outpatients aged ≥65 years with a first unprovoked venous thromboembolism from 9 Swiss hospitals. Patients and managing physicians were blinded to testing results. The outcome was recurrent symptomatic venous thromboembolism during follow-up. We examined the association between the Factor V Leiden and the prothrombin G20210A mutation and venous thromboembolism recurrence using competing risk regression, adjusting for age, sex, and periods of anticoagulation as a time-varying covariate.

Results

Overall, 9.0% of patients had a Factor V Leiden and 3.7% had a prothrombin G20210A mutation. At 36 months of follow-up, patients with a Factor V Leiden and a prothrombin G20210A mutation had a cumulative incidence of recurrent venous thromboembolism of 12.9% (95% confidence interval [CI], 5.1%-30.8%) and 18.5% (95% CI, 4.9%-56.5%), respectively, compared with 16.7% (95% CI, 12.5%-22.1%) of patients without mutation (P = .91 by the log-rank test). After adjustment, neither the Factor V Leiden (sub-hazard ratio 0.98; 95% CI, 0.35-2.77) nor the prothrombin G20210A mutation (sub-hazard ratio 1.15; 95% CI, 0.25-5.19) was associated with recurrent venous thromboembolism.

Conclusion

Our results suggest that testing for genetic thrombophilia may not be beneficial in elderly patients with a first unprovoked venous thromboembolism.  相似文献   

20.

Objectives

This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.

Background

Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.

Methods

In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (n = 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (n = 709); and 3) dose-adjusted warfarin plus DAPT (n = 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics.

Results

Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups).

Conclusions

Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543)  相似文献   

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