Direct oral anticoagulant plasma levels in hospitalized COVID-19 patients treated with dexamethasone.

Direct oral anticoagulants (DOACs) are not recommended in COVID-19 patients receiving dexamethasone because of potential drug-drug and drug-disease interactions affecting anticoagulant concentration and activity. To evaluate short- and long-term pharmacokinetic interactions, serial through and peak DOAC plasma levels were prospectively measured during and after dexamethasone therapy, as well as during the acute phase and after recovery from COVID-19 in hospitalized, non-critically ill patients undergoing treatment with DOACs. Thirty-three (18 males, mean age 79 years) consecutive patients received DOACs (17 apixaban, 12 rivaroxaban, 4 edoxaban) for atrial fibrillation (n = 22), venous thromboembolism (n = 10), and acute myocardial infarction (n = 1). Twenty-six patients also received dexamethasone at a dose of 6 mg once daily for a median of 14 days. Trough DOAC levels on dexamethasone were within and below expected reference ranges respectively in 87.5 and 8.3% of patients, with no statistically significant differences at 48-72 h and 14-21 days after dexamethasone discontinuation. Peak DOAC levels on dexamethasone were within expected reference ranges in 58.3% of patients, and below ranges in 33.3%, of whom over two thirds had low values also off dexamethasone. No significant differences in DOAC levels were found during hospitalization and after resolution of COVID-19. Overall, 28 patients were discharged alive, and none experienced thrombotic or bleeding events. In this study, dexamethasone administration or acute COVID-19 seemed not to affect DOAC levels in hospitalized, non-critically ill COVID-19 patients.

Anamnestic frailty phenotype and adverse outcomes in patients treated with direct oral anticoagulants: Validation and comparative performance with frailty phenotype.

AIMS: The anamnestic frailty phenotype (AFP) is a quick, instrument-free tool derived from frailty phenotype (FP). We prospectively evaluated the discriminative capacity and prognostic value of AFP in ambulatory patients receiving DOACs for atrial fibrillation (AF) or venous thromboembolism (VTE), and compared AFP performance with that of FP. METHODS AND RESULTS: Sensitivity, specificity, positive and negative predictive value (PPV, NPV) with corresponding 95% confidence intervals (95%CI), were estimated for bleeding, thromboembolism, and all-cause mortality. Risk ratios (RRs) were calculated in frail versus non-frail patients. Of 236 patients (median age 78 years), 98 (42%) and 89 (38%) were classified as frail according to FP and AFP, respectively (Kappa= 0.76). Frailty, as assessed by AFP, was associated with higher risk of bleeding (RR 2.3; 95%CI, 1.2 to 4.6), and mortality (RR 4.4; 95%CI, 1.3 to 19.7). Similarly, to FP, AFP exhibited modest sensitivity and specificity, but high NPV that was 91% (95%CI, 85 to 95) for bleeding, 98% (95%CI, 94 to 100) for thromboembolism, and 98% (95%CI, 94 to 100) for mortality. CONCLUSION: Among patients receiving DOACs for AF or VTE, AFP was associated with an increased risk of adverse outcomes. AFP exhibited modest sensitivity and specificity, but excellent NPV. If confirmed, these findings suggest that AFP may represent a rapid, easy-to-use and unexpensive tool that may potentially help identify patients at lower risk for adverse outcomes and tailor anticoagulation management.

Age- versus clinical pretest probability-adjusted D-dimer to rule out lower-extremity deep vein thrombosis in ambulatory patients with active cancer.

BACKGROUND: In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain. AIM: To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule. PATIENTS AND METHODS: Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism. RESULTS: Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate. CONCLUSIONS: In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting.

Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants.

BACKGROUND: Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC-treated patients at higher risk of adverse clinical outcomes. METHODS: Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre-frail, or non-frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non-major bleeding, arterial and venous thromboembolism, and all-cause mortality. RESULTS: 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety-eight (41%) patients were frail, 115 (49%) pre-frail, and 23 (10%) non-frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non-frail or pre-frail patients. Over a median follow-up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre-frail, respectively, while no study outcome occurred among non-frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre-frail and non-frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6). CONCLUSION: In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all-cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis.

Exploring treatments for drooling in children with neurological disorders.

Introduction: Drooling represents a major problem in the every-day life of pediatric patients with neurological disorders. The significant burden, both physical and socio-psychological, of the disorder requires adequate clinical evaluation and proper management. However, treating drooling remains a challenge for clinicians. This is a review of the most up-to-date therapeutic options for the treatment of drooling in the pediatric population, hence both conservative, pharmacological, and surgical approaches are discussed. Areas covered: Randomized clinical trials (RCTs), structured reviews, and case reports are included. Special focus is paid on the methods used to evaluate the efficacy and safety outcomes in the selected RCTs, trying to promote the use of more validated scales to assess drooling in the future. Expert opinion: The lack of reliable metrics to assess efficacy and safety outcomes in drooling limits researchers from identifying the best patient-suitable treatment. The relatively small number of clinical trials carried out over the last two decades is also due to the difficulty in assessing drooling using subjective scales. A key enabler for new efficient therapies stands in the introduction of accurate and robust metrics to measure treatment effectiveness on drooling.