A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow® Assay.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

BACKGROUND: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Evaluating the Use of Unfractionated Heparin with Intra-Aortic Balloon Counterpulsation.

BACKGROUND: Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. OBJECTIVES: The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). METHODS: This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. RESULTS: Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67-196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. CONCLUSIONS: We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting.

Quetiapine for the Treatment of Pediatric Delirium.

BACKGROUND: Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE: The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS: A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS: This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE: Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding With Cardiac Surgery.

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

Real world prescribing practices of apixaban or rivaroxaban lead-in doses for the treatment of venous thromboembolism in hospitalized patients.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Evaluation of Direct Oral Anticoagulants Versus Warfarin for Intracardiac Thromboses.

ABSTRACT: Intracardiac thrombus (ICT) formation is a common complication of several cardiovascular diseases. Warfarin is recommended for treatment of ICT by guidelines based on observational studies occurring before the advent of nonvitamin K antagonist direct oral anticoagulants (DOACs). We aim to evaluate the current prescribing patterns at our institution and to compare the efficacy and safety profiles of warfarin versus DOACs for ICT. This is a retrospective review of adult patients treated with oral anticoagulation for ICT between May 2013 and December 2019. Our primary end point was complete thrombus resolution. Secondary outcomes included time to resolution of thrombus, treatment failure, and duration of therapy. Safety end points included stroke and systemic embolization (SSE) and bleeding events. A total of 123 patients were included (DOAC n = 61; warfarin n = 62). At baseline, more patients in the DOAC group had anemia [6 (10%) vs. 0 (0%), P = 0.013] and alcohol use disorder [6 (10%) vs. 0 (0%), P = 0.013]. Complete thrombus resolution occurred in 50 (82%) and 46 (74%) patients in the DOAC and warfarin groups, respectively (P = 0.298). There was a shorter time to thrombus resolution in the DOAC group versus the warfarin group {63 days [interquartile range (IQR) 40-138] vs. 123 days [IQR 86-244], P = 0.003}. There were no differences found in SSE or bleeding between the groups [DOAC 11 (19%) vs. warfarin 17 (28%), P = 0.213]. For patients with an ICT, treatment with a DOAC for at least 3 months may be a comparable alternative to warfarin in safety and efficacy.

Clinical Use of Cangrelor After Percutaneous Coronary Intervention in Patients Requiring Mechanical Circulatory Support.

BACKGROUND: Patients with cardiogenic shock after percutaneous coronary intervention (PCI) may require mechanical circulatory support (MCS). The combination of dual antiplatelet therapy with cangrelor and continuous anticoagulation required for MCS may increase the risk of bleeding. OBJECTIVE: The objective of the study is to describe the complications and outcomes of patients who received cangrelor during MCS following PCI. METHODS: This is a single-center, retrospective, observational case series of 17 patients who received cangrelor while on MCS from June 2017 to September 2019. RESULTS: In a case series of 17 patients, 8 patients (47%) were supported with an Impella device and 4 patients (24%) with venoarterial (VA) extracorporeal membrane oxygenation (ECMO); 5 required (29%) concomitant VA ECMO and Impella support in the setting of cardiogenic shock. All patients received triple antithrombotic therapy with aspirin, heparin, and cangrelor. Cangrelor was commonly initiated at a median dose of 0.75 (range 0.5-4) µg/kg/min. Cangrelor dose adjustments included changes in increments up to 0.25 µg/kg/min with review of P2Y12 levels. A total of 10 patients (59%) experienced a bleeding event, most commonly located at the peripheral cannulation site (40%) and in the gastrointestinal tract (30%). Seven (70%) and 3 (30%) of the bleeding complications were classified as major and minor, respectively. No patient developed in-stent thrombosis during the hospitalization; 14 (82%) patients survived their MCS course. CONCLUSION AND RELEVANCE: This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

Initial tacrolimus weight-based dosing strategy in allogeneic hematopoietic stem-cell transplantation.

Tacrolimus is a mainstay medication for graft-versus-host disease (GVHD) prophylaxis in combination with other immunosuppressive agents. Achieving therapeutic tacrolimus levels is vital in preventing acute GVHD (aGVHD), while supratherapeutic levels may increase risk of toxicity and relapse. We performed a single center retrospective chart review including all adult patients post-allogeneic hematopoietic stem-cell transplantation who received initial tacrolimus continuous intravenous infusion for GVHD prophylaxis between June 1, 2017 and December 31, 2019. The primary outcome was the percent of patients with an initial therapeutic tacrolimus level, defined as 5-12 ng/mL, after empiric weight-based dosing at 0.02 mg/kg/day. Secondary outcomes included evidence of tacrolimus toxicity within seven days of initiation, incidence of aGVHD by day 100, and relapse after six months. An initial therapeutic level was achieved in 47% of patients with a median initial level of 12.4 ng/mL. Fifty-two percent of patients had supratherapeutic levels. No significant nephrotoxicity, hepatotoxicity, or neurotoxicity occurred within a week of starting tacrolimus or at neutrophil engraftment. Grade II-IV aGVHD by day 100 was observed in 22% of patients, and relapse after six months was found in 16% of patients. These results have led to consideration of an empiric 20% dose reduction to 0.016 mg/kg/day or an expanded initial tacrolimus target of 5-15 ng/mL as there was low aGVHD incidence and no increased risk of toxicity.

Intravenous push versus intravenous piggyback beta-lactams for the empiric management of gram-negative bacteremia.

WHAT IS KNOWN AND OBJECTIVE: Nationwide shortages of small-volume parenteral solutions (SVPS) compelled hospitals to develop strategies including the use of intravenous push (IVP) administration of antibiotics to reserve SVPS for absolute necessities. It is unknown if administration of beta-lactam antibiotics (BL) via IVP results in worse clinical outcomes compared to intravenous piggyback (IVPB) due to the potential inability to achieve pharmacodynamic targets. METHODS: Our health-system implemented a mandatory IVP action plan for BL from October 2017 to September 2018. This was a retrospective study of adult patients with GNB who received empiric therapy with IVPB (30 minutes) or IVP (5 minutes) cefepime (FEP) or meropenem (MEM) for at least 2 days. Endpoints included clinical response, microbiological clearance and mortality. All data are presented as n (%) or median (interquartile range). RESULTS: The final cohort included 213 patients (IVPB n = 105, IVP n = 108). The primary source of bacteremia was urinary, with Escherichia coli being the primary pathogen. Escalation of therapy was similar between groups (15 [14%] vs 11 [10%], P = .36) at a median of 3 days (P = .68). No significant differences were observed in any secondary endpoints including microbiological clearance, bacteremia recurrence, time to defervescence, WBC normalization, vasopressor duration or in-hospital mortality. WHAT IS NEW AND CONCLUSION: Our findings suggest no differences in clinical response with the use of IVP compared to IVPB FEP and MEM for treatment of GNB. This form of administration may be considered as a fluid conservation strategy in times of shortage.

Nasal Reconstruction Using a Myocutaneous Island Pedicle Flap Based on the Nasalis Muscle With Bilevel Undermining: Review of 57 Cases.

BACKGROUND: Nasal reconstruction after Mohs resection of skin cancer commonly uses local flaps, many of which present limitations concerning their movement and skin color/texture match. In this article, the use of a myocutaneous island pedicle flap based on the nasalis muscle with bilevel undermining for the management of defects at challenging locations on the nose is described as a versatile and cosmetically appropriate flap option. In addition, a novel mathematical sizing methodology for this flap is presented. METHODS: Between March 2013 and May 2016, 57 patients having undergone Mohs resection of skin cancer underwent nasal reconstruction using a myocutaneous island pedicle flap based on the nasalis muscle with bilevel undermining at our clinic. During the postoperative follow-up, patients were monitored for complications and received proper wound care. RESULTS: The mean age was 68.4 (range, 34-94) years. The mean follow-up was 10.1 (range, 3.0-34.9) months. The mean defect size was 1.99 (range, 0.70-5.25) cm2. No complete losses of flap occurred. Incidence of minor complications (pin cushion effect, minor delayed healing, etc) was minimal (4/57; 7.0%). Two of the cases in this series involved the utilization of cartilage grafts in combination with the myocutaneus island pedicle flap. CONCLUSIONS: The myocutaneous island pedicle flap based on the nasalis muscle with bilevel undermining can be used as a versatile flap for the closure of defects of various sizes and locations on the nose because of its rich blood supply, ease and convenience of use, and highly acceptable cosmetic outcome.

Outcomes of COVID-19 Patients Hospitalized at Acute Care Services: Real-World Experience in the New York Metropolitan Area During the Early Pandemic Before Initiation of Clinical Trials.

As New York became the epicenter of the COVID-19 pandemic early on, clinicians were challenged to provide optimal medical and pharmaceutical care, despite the paucity of supporting literature and guidance. We sought to describe prescribing patterns and outcomes of physician response to the urgent need to treat COVID-19 patients before initiation of randomized clinical trials. METHODS: This was a retrospective cohort study of adult patients with COVID-19 initially admitted to acute care services during March 2020. Critically ill patients requiring intensive care unit level of care on admission were excluded. RESULTS: A total of 639 consecutive patients (supportive care, n = 247; treatment n = 392) were included in the analysis. Overall, the 28-day mortality rate was 12.2%. The mortality was 8.7% higher in the treatment group (15.6% vs 6.9% in the supportive care group, P < 0.001). Treatment was not protective against progression to severe disease (18.4% vs 3.6% with supportive care, P < 0.0001). Time to defervescence, duration of oxygen support, and hospital and intensive care unit (ICU) length of stay were also higher in the treatment group. In multivariate analysis, 60 years or older, presence of severe disease, and need for ICU admission were identified as independent predictors of 28-day mortality. There were 41 (10.5%) adverse event in the treatment group, with the majority being QT prolongation and gastrointestinal effects. CONCLUSIONS: In this cohort of hospitalized patients admitted to acute care services, treatment with hydroxychloroquine, lopinavir/ritonavir or both could not be shown to improve mortality, progression to severe disease, or clinical response.

Is P&T Ready to Add Rapid Cycle Analytics to Formulary?

Purpose: The intent of this article is to evaluate a novel approach, using rapid cycle analytics and real world evidence, to optimize and improve the medication evaluation process to help the formulary decision making process, while reducing time for clinicians. Summary: The Pharmacy and Therapeutics (P&T) Committee within each health system is responsible for evaluating medication requests for formulary addition. Members of the pharmacy staff prepare the drug monograph or a medication use evaluation (MUE) and allocate precious clinical resources to review patient charts to assess efficacy and value. We explored a novel approach to evaluate the value of our intravenous acetaminophen (IV APAP) formulary admittance. This new methodology, called rapid cycle analytics, can assist hospitals in meeting and/or exceeding the minimum criteria of formulary maintenance as defined by the Joint Commission Standards. In this particular study, we assessed the effectiveness of IV APAP in total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. We assessed the correlation to same-stay opioid utilization, average length of inpatient stay and post anesthesia care unit (PACU) time. Conclusion: We were able to explore and improve our organization's approach in evaluating medications by partnering with an external analytics expert to help organize and normalize our data in a more robust, yet time efficient manner. Additionally, we were able to use a significantly larger external data set as a point of reference. Being able to perform this detailed analytical exercise for thousands of encounters internally and using a data warehouse of over 130 million patients as a point of reference in a short time has improved the depth of our assessment, as well as reducing valuable clinical resources allocated to MUEs to allow for more direct patient care. This clinically real-world and data-rich analytics model is the necessary foundation for using Artificial or Augmented Intelligence (AI) to make real-time formulary and drug selection decisions.

The Interaction Between Rosuvastatin and Ticagrelor Leading to Rhabdomyolysis: A Case Report and Narrative Review.

OBJECTIVE: Drug interactions are a common cause of morbidity and mortality and may require prompt discontinuation of therapeutic regimens due to harmful side effects. Patients with acute coronary syndromes are likely to be prescribed multiple medications that are metabolized through the cytochrome P450 system, increasing the probability for drug interaction. Atorvastatin and simvastatin are both well known to interact with the oral P2Y12 agent ticagrelor. The purpose of this paper is to describe the interaction of ticagrelor with rosuvastatin leading to rhabdomyolysis, which is less clearly defined in the literature. METHOD: We report a case of a 74-year-old male who presented with bilateral lower extremity weakness and difficulty ambulating for one month after being prescribed ticagrelor for a drug eluting stent, in the setting of already being on rosuvastatin. His clinical picture and laboratory findings were consistent with a diagnosis of rhabdomyolysis. His medications were adjusted to a regimen of clopidogrel and alirocumab. One month later, he returned to his baseline status. RESULTS: The mechanism of interaction between rosuvastatin and ticagrelor appears to be multifactorial. It may be caused by CYP450-mediated metabolism from a small amount of crossover between isoenzymes. Ticagrelor may also cause acute kidney injury, increasing the concentration of rosuvastatin. Other mechanisms of interaction include genetic differences in the organic anion transporter polypeptides and transportation through p-glycoprotein. CONCLUSION: Future pharmacokinetic studies are warranted to better understand the interaction.

Perils of Antithrombotic Transitions: Effect of Oral Factor Xa Inhibitors on the Heparin Antifactor Xa Assay.

BACKGROUND: Oral factor Xa inhibitors (OFXais) may interfere with the heparin antifactor Xa (antiXa) assay. The best method to measure heparin activity during the transition from an OFXai to intravenous (IV) unfractionated heparin (UFH) remains unknown. This study aimed to assess the safety and effectiveness of transitioning from an OFXai to UFH. METHODS: A retrospective analysis was conducted of patients with supratherapeutic antiXa levels on UFH who received either apixaban or rivaroxaban within 72 hours before UFH initiation at NYU Langone Health. The primary objective was to identify the incidence of interference on the heparin antiXa assay due to OFXai exposure in the previous 72 hours. The secondary outcomes included the indication for transition to UFH and the rate of thromboembolic and bleeding events. RESULTS: A total of 93 patients with supratherapeutic antiXa activity levels with prior OFXai use were reviewed. Moderate renal impairment, defined as creatinine clearance less than 49 mL/min, was present in 67 (72%) patients. The primary indication for transition from OFXai to UFH was in anticipation for a procedure, and it occurred in 37 (40%) patients. There were 3 major bleeding events and 3 clinically relevant nonmajor bleeding events. No thromboembolic events occurred. CONCLUSIONS: This study assessed the prevalence of supratherapeutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Health care systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient's underlying thromboembolic and bleeding risks.

Sedation Requirements in Patients on Venovenous or Venoarterial Extracorporeal Membrane Oxygenation.

Background:There is a paucity of data evaluating optimal dosing strategies of commonly utilized opioids and sedatives for patients on extracorporeal membrane oxygenation (ECMO) support where pharmacokinetic and pharmacodynamic variables of these administered agents are altered. Objective: To assess the daily dosing requirement of sedatives and analgesics for patients on venovenous (VV) and venoarterial (VA) ECMO after the initial ECMO cannulation period. Methods: We performed a retrospective, observational study of adult patients receiving sedation and analgesia while receiving ECMO support for at least 24 hours. Patients cannulated at an outside hospital more than 24 hours before transfer, those with a history of intravenous drug use or acute alcohol withdrawal, or those who died within 48 hours of ECMO initiation were excluded. Results: We evaluated 26 patients on ECMO, including 13 on VV and 13 on VA ECMO. The median dose of fentanyl was 140 µg/h, with the VV group requiring a higher dose compared with the VA group (167 vs 106 µg/h, P < 0.001). The median doses of dexmedetomidine and propofol were 0.7 µg/kg/h and 26 µg/kg/min, respectively, with no significant differences between groups (P = 0.38 and P = 0.24, respectively). The median daily doses of fentanyl, dexmedetomidine, and propofol did not significantly increase throughout the time on ECMO support. Conclusions and Relevance: We found that the overall opioid daily dosing requirements were lower than previously reported in the literature. Additionally, light sedation strategies with a target RASS of -1 to 0 are feasible in this patient population.

The Safety of Midline Catheters for Intravenous Therapy at a Large Academic Medical Center.

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.