Racial differences in P2Y12 inhibitor responsiveness in patients undergoing neuro-endovascular procedures: A cohort from the Middle East.

BACKGROUND: Data on P2Y12 inhibitors responsiveness from the middle east is scarce. We sought to investigate patient responsiveness to P2Y12 inhibitors within a cohort of major races that characterize the UAE population. The secondary objective was to assess risk factors for hyper and hypo-responsiveness in this population. METHODS: We conducted a cross-sectional study on adults who received either clopidogrel or ticagrelor treatments and had platelet responsiveness testing before undergoing neuro-endovascular interventions at our quaternary care hospital between March 2015 and April 2019. RESULTS: During the study period, 249 subjects met the inclusion criteria. Overall, 17.3 % were hyper-responsive and 25.7 % were hypo-responsive to P2Y12 inhibitors. When comparing between the P2Y12 inhibitors, rates of hyper-responsiveness were significantly higher to ticagrelor when compared to clopidogrel (11 versus 6 %, p = 0.02 respectively). Contrarily, hypo-responsiveness rates were significantly higher in clopidogrel treated patients compared to their ticagrelor treated counterparts (23 versus 2 %, p < .001 respectively). Patients of Middle-Eastern origin showed a significantly higher rate of hypo-responsiveness to both clopidogrel and ticagrelor when compared to other races (41.1 % and 26.7 %, P < 0.001 respectively). Asians showed the highest rates of hyper-responsiveness for both agents. Multivariate logistic regression analysis showed that proton pump inhibitors and statin combination, (OR: 6.39, 95 %CI [1.60, 25.392]), and Middle East vs. Indian subcontinent patients (OR: 4.67, 95 %CI [1.79-12.14]) were independent predictors of hypo-responsiveness to both P2Y12 inhibitors. CONCLUSION: This study demonstrated a high rate of hypo-responsiveness to P2Y12 inhibitors in a UAE cohort of patients undergoing neuro-endovascular procedures. In addition, therapeutic responsiveness to P2Y12 inhibitors varied markedly based on the racial background. Future larger studies are needed to evaluate genetic variations that may contribute to this rate of hypo-responsiveness in our population.

A Case of Hemorrhagic Cholecystitis in a Patient on Apixaban After COVID-19 Infection.

BACKGROUND Hemorrhagic cholecystitis is a rare cause of abdominal pain, which can result from malignancy, bleeding, or trauma. The presentation, which includes right upper-quadrant pain, nausea, and vomiting, can overlap with other disease states, thereby rendering the diagnosis challenging. CASE REPORT We describe a patient taking apixaban wo had paroxysmal atrial fibrillation with history of joint pain on long-term steroids who developed hemorrhagic cholecystitis following an episode of pneumonia secondary to SARS-CoV-2 virus (COVID-19) infection. The hospital COVID-19 pneumonia protocol included the administration of steroids and symptomatic care. Following discharge, he presented to our hospital with a sudden onset of severe abdominal pain and distention accompanied by elevated liver enzymes and a low hemoglobin level of 78 g/L. Magnetic resonance cholangiopancreatography revealed a distended gallbladder and intraluminal layering, early subacute blood products, and increased wall thickness, which was thought to represent non-calcular hemorrhagic cholecystitis. Furthermore, a stable 18×16×20 mm cyst in the tail of the pancreas was also located posteriorly, with indentation to the splenic vein. The patient was managed conservatively, and the pain subsided on day 3 after admission. CONCLUSIONS Hemorrhagic cholecystitis is rarely reported with the use of the direct oral anticoagulants (DOACs). In our case the combination of a recent COVID-19 hospitalization, steroid use, and possible pancreatic cancer (CA 19-9 288.4 kU/L) may have contributed to such incidence in the setting of apixaban utilization; however, it is not possible to make definitive correlations. Investigating hemorrhagic cholecystitis in the setting of DOAC use in patients with multiple risk factors such as those that existed in our patient is imperative for proper diagnosis and management.

QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. METHODS: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). RESULTS: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test). CONCLUSION: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

Y-site Administration of Imipenem/Cilastatin/Relebactam With Common Intravenous Medications.

PURPOSE: Imipenem/cilastatin/relebactam has shown efficacy in complicated intra-abdominal and urinary tract infections in the RESTORE IMI-1 study, and it was recently approved by the US Food and Drug Administration. A press release announced that another Phase III study (RESTORE IMI-2) in patients with hospital-acquired and ventilator-associated pneumonia has met the primary end point. Critically ill patients with multidrug-resistant infections are expected to receive several pharmaceutical intravenous drugs while admitted in hospitals, warranting the need for Y-site compatibility studies. This study was conducted to evaluate the physical compatibility of imipenem/cilastatin/relebactam for injection during Y-site administration with common injectable intravenous medications. METHODS: Imipenem/cilastatin/relebactam was prepared to the concentration of 5 mg/mL, and other intravenous tested drugs were reconstituted as per the package inserts. Y-site was simulated as a 2-drug combination by mixing 5 mL of each in a glass tube, with reversing of the order of mixing; physical characteristics were recorded, and pH changes and turbidity were measured at time intervals. FINDINGS: Imipenem/cilastatin/relebactam was found to be compatible with a wide range of intravenous medications, facilitating co-administration with various IV medications. IMPLICATIONS: The compatibility reported is limited to a 2-h observation period in this study to adequately cover imipenem/cilastatin/relebactam infusion time. In addition, it is based on the measured turbidity with no chemical assay of the components of the admixture.

Outcomes Associated with Conventional Accelerated Versus Once-Weekly IV Iron Therapy in Outpatients Undergoing Hemodialysis.

BACKGROUND: Although parenteral iron replacement is a key aspect of managing anemia in patients who are undergoing hemodialysis, studies evaluating novel iron dosing regimens are scarce. OBJECTIVE: To compare the effectiveness of a once-weekly IV iron dosing strategy with that of a conventional accelerated iron dosing regimen in patients undergoing hemodialysis. METHODS: In this retrospective cohort study, patient-specific information was collected for individuals undergoing hemodialysis who received IV iron between June 1, 2010, and June 30, 2012, at a community hospital in southwestern Ontario. The primary outcomes were hemoglobin level and utilization of an erythropoiesis-stimulating agent for 2 groups of patients: those receiving iron according to a once-weekly IV regimen and those receiving iron by a conventional accelerated IV regimen. RESULTS: Of the 148 patients who met the inclusion criteria, 99 (66.9%) received iron by a conventional accelerated regimen and 49 (33.1%) by a once-weekly IV regimen. Generalized estimating equations developed from 313 observations obtained from these 148 patients suggested that average transferrin saturation percentage and iron concentration were both significantly higher in the group that received iron once weekly than in the group that received iron by the conventional accelerated regimen (p = 0.014 and 0.008, respectively). The mean weekly dose of erythropoiesis-stimulating agent was significantly lower in the once-weekly administration group than in the conventional administration group (7419 versus 10 706 units; p = 0.041). The 2 groups did not differ significantly in terms of hemoglobin concentration (p = 0.46) or ferritin level (p = 0.13). CONCLUSIONS: The findings of this study suggest that a once-weekly iron dosing regimen may be superior to a conventional accelerated dosing regimen for managing iron deficiency anemia in patients who are undergoing hemodialysis.

CONTEXTE: Bien que la recharge en fer par voie parentérale représente un facteur clé de la prise en charge de l'anémie de patients traités par hémodialyse, il n'y a que très peu d'études évaluant les nouveaux schémas posologiques de fer. OBJECTIF: Comparer l'efficacité réelle d'une dose hebdomadaire de fer administrée par voie intraveineuse à celle d'un schéma posologique intensif traditionnel de fer chez les patients hémodialysés. MÉTHODES: Dans la présente étude de cohorte rétrospective, on a recueilli des données sur des patients traités par hémodialyse qui ont reçu du fer par voie intraveineuse entre le 1er juin 2010 et le 30 juin 2012 dans un hôpital communautaire du sud-ouest de l'Ontario. Les principaux paramètres d'évaluation étaient le taux d'hémoglobine et l'emploi d'un agent stimulant l'érythropoïèse chez deux groupes de patients : l'un recevant du fer à raison d'une dose hebdomadaire par voie intraveineuse et l'autre selon un schéma posologique intensif traditionnel par voie intraveineuse. RÉSULTATS: Parmi les 148 patients ayant satisfait aux critères d'admissibilité, 99 (66,9 %) ont reçu du fer selon un schéma posologique intensif traditionnel et 49 (33,1 %) l'ont reçu à raison d'une dose hebdomadaire par voie intraveineuse. Des équations d'estimation généralisée élaborées à partir de 313 observations obtenues de ces 148 patients laissent croire que les pourcentages moyens de saturation de la transferrine et de la concentration de fer étaient tous deux nettement plus élevés dans le groupe ayant reçu du fer une fois par semaine que dans le groupe en ayant reçu selon le schéma posologique intensif traditionnel (respectivement p = 0,014 et 0,008). La dose hebdomadaire moyenne d'un agent stimulant l'érythropoïèse était significativement plus faible au sein du groupe recevant une dose de fer hebdomadaire que dans le groupe de traitement traditionnel (7 419 contre 10 706 unités; p = 0,041). Les taux d'hémoglobine (p = 0,46) ou de ferritine (p = 0,13) ne variaient pas de façon significative entre les deux groupes. CONCLUSIONS: Selon les résultats de la présente étude, une dose hebdomadaire de fer serait plus efficace que le schéma posologique intensif traditionnel pour traiter l'anémie par carence en fer chez les patients hémodialysés.