Showing papers by "Alfonso Tafur published in 2021"

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Abstract: Importance Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, setting, and participants The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main outcomes and measures The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P Conclusions and relevance In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial registration ClinicalTrials.gov Identifier: NCT04401293.

Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19.

Abstract: Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination.

Abstract: Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

Abstract: Background One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. Management Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. Current Issues The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. Perspectives There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). Conclusion The “PDA strategy” integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

TEMPORARY REMOVAL: Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis

Abstract: The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Prognostic Value of Venous Thromboembolism Risk Assessment Models in Patients with Severe COVID-19

Abstract: Introduction Severe novel corona virus disease 2019 (COVID-19) causes dysregulation of the coagulation system with arterial and venous thromboembolism (VTE). We hypothesize that validated VTE risk scores would have prognostic ability in this population. Methods Retrospective observational cohort with severe COVID-19 performed in NorthShore University Health System. Patients were >18 years of age and met criteria for inpatient or intensive care unit (ICU) care. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) and Caprini scores were calculated and patients were stratified. Results This study includes 184 patients, mostly men (63.6%), Caucasian (54.3%), 63 years old (interquartile range [IQR]: 24-101), and 57.1% of them required ICU care. Twenty-seven (14.7%) thrombotic events occurred: 12 (6.5%) cases of disseminated intravascular coagulation (DIC), 9 (4.9%) of pulmonary embolism, 5 (2.7%) of deep vein thrombosis, and 1 (0.5%) stroke. Among them, 86 patients (46.7%) died, 95 (51.6%) were discharged, and 3 (1.6%) were still hospitalized. "Moderate risk for VTE" and "High risk for VTE" by IMPROVE score had significant mortality association: (hazard ratio [HR]: 5.68; 95% confidence interval [CI]: 2.93-11.03; p < 0.001) and (HR = 6.22; 95% CI: 3.04-12.71; p < 0.001), respectively, with 87% sensitivity and 63% specificity (area under the curve [AUC] = 0.752, p < 0.001). "High Risk for VTE" by Caprini score had significant mortality association (HR = 17.6; 95% CI: 5.56-55.96; p < 0.001) with 96% sensitivity and 55% specificity (AUC = 0.843, p < 0.001). Both scores were associated with thrombotic events when classified as "High risk for VTE" by IMPROVE (HR = 6.50; 95% CI: 2.72-15.53; p < 0.001) and Caprini scores (HR = 11.507; 95% CI: 2.697-49.104; p = 0.001). Conclusion The IMPROVE and Caprini risk scores were independent predictors of mortality and thrombotic events in severe COVID-19. With larger validation, this can be useful prognostic information.

Treatment-Dose LMWH versus Prophylactic/Intermediate Dose Heparins in High-Risk COVID-19 Inpatients: Rationale and Design of the HEP-COVID Trial.

Abstract: Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels Conflicting data have yet to elucidate optimal thromboprophylaxis dosing HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4 Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 05 mg/kg (CrCl 15–30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD The principal safety outcome is major bleeding Events are adjudicated locally Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge

National Trends for Peripheral Artery Disease and End Stage Renal Disease From the National Inpatient Sample Database.

Abstract: Peripheral artery disease (PAD), and subsequent chronic limb-threatening ischemia (CLTI), are frequently encountered among patients with end-stage renal disease (ESRD). Their coexistence is less favorable in comparison to patients with ESRD alone. We sought to investigate trends, comorbidities, determinants for cost, and prognostic outcomes in patients with concomitant ESRD and PAD. A retrospective analysis was performed using data from the National Inpatient Sample database from the years 2005-2014. ICD-9 codes were used to identify patients with diagnoses of PAD, CLTI, and ESRD. Pearson's Chi-square, T-test, ANOVA, and multivariate binary logistic regression were used in this analysis. 7,214,843 patients with ESRD were identified. Of these, 123,499 patients were diagnosed with PAD and 102,447 with CLTI. Compared to ESRD alone, mortality rates increased with PAD and CLTI (5.7% vs. 13.9% vs. 15.9%, P < 0.001). Length of stay in days (7.3 vs. 10.2 vs. 11.1, P < 0.001) and in-hospital costs (59,872 vs. 85,866 vs. 89,016, P < 0.001) were higher with PAD and CLTI, respectively. CLTI demonstrated the highest independent predictor of mortality [OR = 6.93 (6.43-7.46), P < 0.001]. A decreasing trend in the rate of PAD (2005: 1.9% vs. 2014: 1.4%, P < 0.001) and CLTI (2005: 1.6% vs. 2014: 1.1%, P < 0.001) was noted. The presence of coexisting PAD, and furthermore CLTI, in patients with ESRD significantly raised in-hospital mortality, cost, and length of stay. A negative trend in rates of PAD and CLTI were observed. Proactive identification of this high-risk population may lead to accurate diagnosis and tailored therapeutic strategies.

Comparison of a nonpneumatic device to four currently available intermittent pneumatic compression devices on common femoral blood flow dynamics.

Abstract: Objective The purpose of the present study was to compare common femoral vein blood flow enhancement during external mechanical compression using the novel, nonpneumatic Recovery Force Health Movement and Compressions (MAC) System (Recovery Force USA, Fishers, Ind), and four currently available intermittent pneumatic compression devices. Methods The MAC device was compared with the Kendall SCD 700 (Cardinal Health, Dublin, Ohio), Arjo Huntleigh Flowtron ACS900 (Arjo, Malmo, Sweden), ActiveCare+S.F.T. (Zimmer Biomet, Warsaw, Ind), and Circul8 (Ortho8, Rocklin, Calif). Doppler ultrasound measurements for each device were directly obtained from the right common femoral vein by a registered vascular technologist. The peak flow velocity and the time taken to reach the peak were calculated. For the MAC system only, the subjects were asked to walk a minimum of 500 steps while wearing the system, which was then checked for slippage. Leg size measurements were obtained using the noncontact Sigvaris Legreader XT5 (Vialis Ortopedia, Turin, Italy). The MAC device is not yet commercially available, and the present study was a prequel to clinical studies of venous thromboembolism prevention. Results We recruited a broad range of 20 subjects who varied in age (mean ± standard deviation [SD], 50.5 ± 16.2 years), body mass index (mean ± SD, 26 ± 5.5 kg/m2), gender (male, 25%; female, 75%), and right calf circumference (mean ± SD, 37.2 ± 5.5 cm). The peak flow velocity compared with the baseline measurements was significantly greater for the Recovery Force Health MAC System for three (Kendall SCD 700, P = .02; ActiveCare+S.F.T., P = .003; Circul8, P Conclusions The MAC System is a mobile device that remained in place during ambulation and provided more consistent external mechanical compression in the desired range compared with the other three devices included in the present study.