Showing papers by "Alfonso Tafur published in 2017"

The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale

Abstract: Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol. Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group. Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Comparisons Between Upper and Lower Extremity Deep Vein Thrombosis: A Review of the RIETE Registry

Abstract: Background:The outcome of patients with upper extremity deep vein thrombosis (UEDVT) has not been consistently compared with that in patients with lower extremity deep vein thrombosis (LEDVT).Methods:We used the Registro Informatizado de Enfermedad Trombo Embolica (RIETE) registry to compare the outcomes during the course of anticoagulant therapy in patients with UEDVT versus outcomes in patients with LEDVT.Results:As of August 2015, 37,366 patients with acute DVT had been enrolled in RIETE: 35094 (94%) had LEDVT, 1334 (3.6%) non-catheter related UEDVT (672 unprovoked and 662 provoked) and 938 (2.5%) had catheter-related UEDVT. During the course of anticoagulation, patients with unprovoked UEDVT had a higher rate of DVT recurrences (hazard ratio [HR]: 2.22; 95% CI: 1.37-3.43) and a similar rate of PE recurrences or major bleeding than those with unprovoked LEDVT. Patients with non-catheter-related provoked UEDVT had a similar outcome than those with provoked LEDVT. Among patients with UEDVT, those with no...

Catheter-Directed Treatment of Pulmonary Embolism: A Systematic Review and Meta-Analysis of Modern Literature.

Abstract: We summarize the evidence for the safety and efficacy of catheter-directed thrombolysis (CDT) with and without ultrasound-assisted therapy for treating submassive and massive pulmonary embolism (PE) in a systematic review. The primary efficacy outcome was mortality. Outcomes were pooled across studies with the random-effects model. Twenty-four studies enrolled 700 patients in total; 653 received mechanical thromboembolectomy treatments for PE (mortality rate, 9% [95% confidence interval (CI), 6%-13%], P = .12; rate of minor complications, 6% [95% CI, 2%-13%]). In the ultrasound-accelerated thrombolysis (USAT) studies, the mortality rate was 4% (95% CI, 1%-11%) and in the non-USAT studies, it was 9% (95% CI, 6%-13%). Secondary safety outcomes were all bleeding events, which occurred in 12% (95% CI, 7%-20%) of the USAT studies and in 10% (95% CI, 5%-20%) of the non-USAT studies. Current clinical evidence does not prove USAT is superior over CDT methods.

Validation of a Patient-Completed Caprini Risk Score for Venous Thromboembolism Risk Assessment

Abstract: Introduction Individualized risk assessment for venous thromboembolism (VTE) using the Caprini risk score (CRS), coupled with targeted prophylaxis based on the score, is effective in reducing postoperative VTE. Critics contend that using this tool is time consuming for health care providers. We decided to create a patient-completed CRS and conducted a prospective study to compare the scores calculated by a patient with those calculated by a blinded physician for the same patient. Methods In phase 1, we interviewed patients in our deep vein thrombosis (DVT) support group who had a history of thrombosis and included their family members to determine areas of misunderstanding in the original CRS. We created a patient-completed form based on these interviews. In phase 2, we further optimized the questions after a CRS-trained, blinded physician scored 20 hospitalized patients during the pilot study. In the final (third) phase, we measured the agreement level between the new form filled out by the trained physicians and those filled out by the patients. The study was approved by our local institutional review board. Using PASS version 11, we determined that a sample size of 37 individuals achieves a power of 80%, to detect a 0.1 difference between the null hypothesis correlation of 0.5 and the alternative hypothesis correlation of 0.7 using a two-sided hypothesis test with a significance level of 0.05. We tabulated the individuals' answers and categorized the scores by using SPSS version 23 to estimate the kappa value, linear correlation, and the Bland–Altman test. A kappa value greater than 0.8 indicated an “almost perfect agreement.” Results We tested the first patient-completed CRS version (phase 2) in a 20-patient pilot study. A poor agreement was observed with the body mass index (BMI) responses in multiple iterations, and so we excluded the BMI calculation from the final patient-completed CRS form. We recruited 42 patients with an average age of 55, mostly female (45%), who completed less than college education (62%) to fill out the updated CRS form (phase 3). An almost perfect agreement was found for both the individual questions and the overall score comparing physician and patient answers, resulting in a high correlation (r = 0.95). In Bland–Altman, we did not find any trend for extreme values. Conclusion We created and validated a patient-completed CRS form that has an excellent agreement level with the physician-completed form. From the results, the physician only needs to calculate the BMI. The average time for a patient to complete the form was 5 minutes. The average time for the physician to finalize the score was approximately 6 minutes. Implementation studies are needed to assess the correlation of the aggregated score, derived from this form, with the occurrence of perioperative VTE.

Evaluation of the prognostic value of platelet to lymphocyte ratio in patients with hepatocellular carcinoma

Abstract: Background: Hepatocellular carcinoma (HCC) is increasingly common, potentially fatal cancer type globally. Platelet-lymphocyte ratio (PLR) as a biomarker for systemic inflammation has recently been recognized as a valuable prognostic marker in multiple cancer types. The aim of the present study was to assess the prognostic value of PLR in HCC patients and determine the optimal cut-off value for risk stratification. Methods: We retrospectively analyzed patients with diagnosis of HCC (screened by ICD-9 code, confirmed with radiographic examination and/or biopsy) at a large public hospital during 15 years (Jan 2000 through July 2015). PLR, among other serology laboratory values were collected at diagnosis of HCC. Its association with overall survival was evaluated with Cox proportional hazard model. Results: Among 270 patients with HCC, 57 (21.1%) patients died within an average follow-up of 11.9 months. PLR at diagnosis was significantly different between survivors and deceased (128.9 vs . 186.7; P=0.003). In multivariate analysis, aspartate transaminase (AST) (HR 2.022, P Conclusions: Our results indicated that elevated PLR at diagnosis above 220 predicted poor prognosis in HCC patients. PLR is a low-cost and convenient tool, which may serve as a useful prognostic marker for HCC.

Predictors of active cancer thromboembolic outcomes: RIETE experience of the Khorana score in cancer-associated thrombosis

Abstract: Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1–2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99–7.63), 11.2 (95 %CI: 9.91–12.7) and 19.4 (95 %CI: 15.4–24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13–6.56), 10.3 (95 %CI: 9.02–11.7) and 19.4 (95 %CI: 15.4–24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8–28.0), 58.5 (95 %CI: 55.5–61.7) and 120 (95 %CI: 110–131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50–0.56) for recurrent VTE, 0.56 (95 %CI: 0.54–0.59) for major bleeding and 0.54 (95 %CI: 0.52–0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.

Impact of atrial fibrillation on platelet gene expression

Abstract: Aims Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR). Methods and Results RNA from isolated platelets were reverse transcribed, assayed against 15 genes using real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin-like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold-lower (17.0±2.8 vs 12.5±3.8, P<.001), follow by genes encoding for prostacyclin receptor, and for von Willebrand factor which had fourfold lower expression compared to NSR controls. Gender, type of atrial fibrillation, heart failure, hypertension, prior stroke, diabetes mellitus, and atherosclerosis were associated with different gene expression. Following PVI, expression of four genes significantly increased, particularly IGFALS gene (increased 256-fold) and ADAMT gene increased 16-fold); expression of three genes significantly decreased, and expression of eight genes has not changed. Conclusions Platelets are capable to respond to the circulatory environment of NVAF by altering transcript and changing prothrombotic status. This shows platelet potential for molecular “reprogramming” possibly induced by flow disturbances of NVAF.

Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry

Abstract: Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41 %) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI 5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI 18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI: 0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.

Predictors of active cancer thromboembolic outcomes: mortality associated with calf deep vein thrombosis.

Abstract: BACKGROUND Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer. Outcomes, including mortality data, in the cancer population are limited in those with calf deep vein thrombosis (CDVT) compared to individuals with proximal deep vein thrombosis. The aim of this study was to assess the prognosis among patients with active cancer and CDVT. METHODS Single institution inception cohort of cancer-associated CDVT patients who presented with thrombosis distal to popliteal level confirmed objectively by ultrasound. We defined active cancer as metastatic disease or use of chemotherapy at diagnosis. Clinical and laboratory data were extracted from the electronic health records. The Khorana Risk Score (KRS) was extracted based on data at entry. Institutional review board approval was obtained prior to the analysis. Categorical variables are expressed as percentages and continuous variables as median (interquartile range). Kaplan-Meier method, Pearson's χ2, Mann-Whitney U and Cox proportional hazard were applied. SPSS software version 22 was used for all statistics. RESULTS One hundred nine patients (men=44 [40%], Age>65=89 [82%], BMI>30=25 [23%], Smoker=59 [54%]) were included. The majority had a low (30%) or intermediate KRS (64%) at diagnosis. Forty-seven percent died during a median follow-up time of 2.5 years (0.5-3.1). After multivariate analysis, the predictors of mortality were: smoking (hazard ratio [HR] 2.3; 95% CI: 1.2-4.7), metastasis (HR=5.8; 95% CI: 2.9-11.7), gastrointestinal cancer (HR=3.9; 95% CI: 1.8-8.5), and lung cancer (HR=4.1 95% CI: 1.7-10.3). VTE specific variables not associated with mortality included: bilateral CDVT, concomitant pulmonary embolism, multiple vein involvement, filter placement, or a surgery-associated event. The KRS was not predictive of death. CONCLUSIONS Cancer-specific variables and smoking predicted mortality among CDVT patients in this cohort, rather than VTE characteristics at the time of CDVT diagnosis.