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.

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center.

Romiplostim is indicated for immune thrombocytopenia (ITP), though is often used off-label for other indications such as chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia post hematopoietic stem cell transplantation (HSCT). Although romiplostim is FDA approved at a starting dose of 1 mcg/kg, it is often initiated at 2-4 mcg/kg depending on the severity of thrombocytopenia in clinical practice. Given the limited data, but interest in higher doses of romiplostim for indications other than ITP, we aimed to assess our inpatient romiplostim utilization at NYU Langone Health.This was a single-center, retrospective review of 84 adult patients from January 2019 to July 2021. The top three indications were ITP (51, 60.7%), CIT (13, 15.5%), and HSCT (10, 11.9%). The median initial romiplostim dose was 3.8 mcg/kg (range, 0.9-10.8). 51% of patients achieved a platelet count of ≥50 × 109/L by the end of week 1 of therapy. For patients achieving goal platelets by the end of week 1, the median dose of romiplostim was 2.4 mcg/kg (range, 0.9-10.8). There was 1 episode of thrombosis and 1 episode of stroke.We found that higher than FDA-recommended initial doses should be considered to achieve a platelet response. It appears to be safe to initiate romiplostim as higher doses, and to increase doses by greater increments than 1 mcg/kg in order to achieve a platelet response. Future prospective studies are needed to confirm the safety and efficacy of romiplostim in off-label indications and should evaluate clinical outcomes such as bleeding and need for transfusions.

High-dose methotrexate dosing strategy in primary central nervous system lymphoma.

The backbone induction therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) and rituximab, which can be combined with other chemotherapeutic agents. The optimal dose of HD-MTX remains unclear, as doses between 3 and 8 g/m2 have been shown to be effective. In this retrospective study, HD-MTX dosed at 3-5 g/m2 demonstrated an overall response of 81.8%, with 11 (50%) complete responses. The median overall survival was not met at 29 months and median progression free survival was 12.5 months.There were two discontinuations due to nephrotoxicity. The most common adverse event was hepatotoxicity (18.5%), with no treatment-related mortality events observed.Overall, HD-MTX dosed at 3-5 g/m2 demonstrated similar efficacy and lower toxicity compared to higher doses in PCNSL patients. Reducing the initial HD-MTX dose may help ensure tolerability and completion of induction therapy, especially in patients with co-morbidities or older age who have poorer outcomes.

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.

Evaluating the adverse effects of melphalan formulations.

INTRODUCTION: For multiple myeloma patients who respond to primary therapy, autologous hematopoietic stem cell transplant (HSCT) is considered standard of care with high-dose melphalan for transplant candidates. There are now two different melphalan formulations available, including a propylene glycol containing (PG-MEL) product and a propylene glycol-free (PG-free MEL) product. Although considered bioequivalent, there remains limited literature directly evaluating the adverse events between the two agents. We seek to assess the tolerability and severity of side effects between the two formulations in a real-life practice setting. METHODS: A retrospective, descriptive analysis was conducted of multiple myeloma patients who received autologous stem cell conditioning with either melphalan formulation when dosed at 100 mg/m2/dose for two consecutive doses. The primary outcome was the assessment of tolerability and severity of side effects. Tolerability was split into four major categories including hematologic toxicity, gastrointestinal toxicity, renal toxicity, and highest recorded mucositis grade. RESULTS: There were a total of 78 patients who received a melphalan preparation during the study. The median time to myeloablation and neutrophil engraftment was five and seven days post-HSCT, respectively, for all patients. Patients who received PG-free MEL were less likely to develop mucositis, with 22 (56%) reported highest grade 0, defined by World Health Organization oral toxicity scale, compared to those who received PG-MEL (33%), p = 0.04. CONCLUSION: There were minimal differences in tolerability or side effects observed between PG-free MEL and PG-MEL. These data may assist in better understanding the anticipated adverse effects of a high-dose melphalan conditioning therapy.

Anticoagulation prescribing patterns in patients with cancer.

Cancer is a known hypercoagulable state that leads to an increased risk of venous thromboembolism (VTE). Low molecular weight heparin remains the preferred anticoagulant for VTE in patients with cancer over vitamin K antagonist. However, the preferred anticoagulant in prevention of stroke and systemic embolism in atrial fibrillation (AF) in patients with cancer has yet to be determined. The direct oral anticoagulants (DOACs) are increasingly being utilized; however their role in cancer has only recently been investigated. The objective of this retrospective cohort was to describe real-world anticoagulation prescribing patterns in cancer patients at a large academic medical center between January 1, 2013 and October 31, 2016. We sought to assess the safety, tolerability, and efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient demographic, clinical characteristics, as well as bleeding and thrombotic events were collected. There were 214 patients in our analysis, of which 71 patients (33%) received a DOAC [apixaban (n = 22), dabigatran (n = 17), and rivaroxaban (n = 32)]. There were fewer bleeding events and/or discontinuations in the DOAC group compared to enoxaparin (13 vs. 27, p = 0.022). There was no difference in major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or DOAC to warfarin. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients with cancer. DOACs may represent an alternative to warfarin or enoxaparin in patients with cancer for VTE and/or stroke reduction in AF.

Understanding U.S. Physician Satisfaction: State of the Evidence and Future Directions.

Physician satisfaction is an important issue, yet we know less about it than we should. This narrative review updates our knowledge about U.S. physician satisfaction and proposes new foci for understanding and studying the topic that align better with the evolving U.S. healthcare delivery system, physicians' everyday work situations, and medicine's internal demographic changes. Using the PubMed database of empirical studies published between 2008 and 2013 that examine U.S. physician job, career, or work satisfaction, we compare our review findings with a review covering studies published between 1970 and 2007. We included 22 studies in our review. Overall, U.S. physicians experience moderate to high levels of job, work, and career satisfaction, and these levels have remained stable over time. This is surprising given discussions in the popular press of declining physician satisfaction. The observed consistency and the high levels of satisfaction do not tell the entire story. While autonomy, income, and perceived job demands are several of the stronger predictors of physician satisfaction, variables such as age and gender have been understudied. And our understanding of what drives physician satisfaction still draws too heavily on other variables that are less salient given today's workplace and the current trends in professional demographics and employment arrangements. Future thinking and research on physician satisfaction should align more with the array of changes now occurring within the U.S. medical profession and the larger U.S. healthcare delivery system, within which physicians work. To do this, new variables and conceptual thinking that capture these changes must be used.