Prevention and management of acute toxicities from conditioning regimens during hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) remains the only curative option for several hematological malignancies. Its use has continued to grow, with an estimated 23,500 transplants performed annually in the United States alone. The acute toxicities that occur from conditioning chemotherapy can impact the peri-transplant period and have substantial implications on patients' tolerability and outcomes, irrespective of the treatment of their disease. Chemotherapy-induced nausea vomiting (CINV), mucositis, transplant-associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome, also known as a veno-occlusive disease (SOS/VOD) can all have significant implications for patients. These acute complications begin with the start of conditioning chemotherapy and add to potential toxicity for patients throughout the early post-transplant period, from Day +30 for CINV, mucositis, and SOS, and which can continue through at least Day +100 with the onset of TA-TMA. These toxicities must be prevented and managed appropriately. This review will summarize the literature surrounding them and guide their management.

Dispensary Cannabidiol (CBD): Nothing to Worry About!

Introduction: Despite US FDA approval of cannabidiol (CBD) liquid (Epidiolex®), patients with epilepsy still supplement prescription treatments with dispensary CBD. This study aimed to evaluate therapeutic effectiveness of dispensary CBD. Methods: We retrospectively collected dosage information, CBD serum levels, efficacy, and adverse effects from patient charts (children, adolescents, adults) (n = 18). Results: All 18 patients showed no clinical benefit from dispensary CBD as detectable serum levels never reached a therapeutic range of 150 ng/mL (6 patients had barely detectable levels that were below laboratory reporting thresholds). Minute levels of tetrahydrocannabinol (THC) were found in 3 patients, and moderate levels were found in 1 patient. Conclusion: Dispensary CBD failed to reach effective therapeutic levels in all of these patients. The presence of THC demonstrates the current lack of regulation of dispensary CBD. Anecdotal reports of clinical effectiveness should be considered an effect of concomitant prescription antiseizure medications and not dispensary CBD.

An evaluation of injurious falls and Fall-Risk-Increasing-Drug (FRID) prescribing in ambulatory care in older adults.

BACKGROUND: Falls are a major public health problem affecting millions of older adults each year. Little is known about FRID prescribing behaviors after injurious falls occur. The primary objective of this study was to investigate whether an injurious fall is associated with being prescribed a new FRID. METHODS: We conducted a cross-sectional analysis using data from the National Ambulatory Medical Care Survey (2016). We included visits from patients age ≥ 65 years and classified visits based on presence of an injurious fall. The outcome of interest was prescription of new FRID between those with and without an injurious fall. Multivariable logistic regression weighted for sampling and adjusted for demographics, health history and other medications was used. Age and Alzheimer's disease were examined as potential effect measure modifiers. Odds ratios and 95% confidence intervals were reported. Bayes factor upper bounds were also reported to quantify whether the data were better predicted by the null hypothesis or the alternative hypothesis. RESULTS: The sample included 239,016,482 ambulatory care visits. 5,095,734 (2.1%) of the visits were related to an injurious fall. An injurious fall was associated with a non-statistically significant increase in odds of at least one new FRID prescription: adjusted OR = 1.6 (95% CI 0.6, 4.0). However, there was non-statistically significant evidence that the association depended on patient age, with OR = 2.6 (95% CI 0.9, 7.4) for ages 65-74 versus OR = 0.4 (95% CI 0.1, 1.6) for ages ≥ 75. In addition to age, Alzheimer's disease was also identified as a statistically significant effect measure modifier, but stratum specific estimates were not determined due to small sample sizes. CONCLUSIONS: Ambulatory care visits involving an injurious fall showed a non-statistically significant increase in odds of generating a new FRID prescription, but this association may depend on age.

Initial Real-World Experience With Cenobamate in Adolescents and Adults: A Single Center Experience.

BACKGROUND: Following approval by the US Food and Drug Administration (FDA) in late 2019, cenobamate (Xcopri) has been utilized to treat adults with focal seizures. Based on its robust efficacy from the phase 2 trials, we began using cenobamate in our adolescent and young adult patients whose seizures were not controlled with previously available options. This study expanded its real-world application to this cohort with focal epilepsy and a history of drug-related rash. METHODS: We conducted a retrospective study of our patients exposed to cenobamate (n = 45). We evaluated dosage and serum levels, efficacy, drug interactions, and adverse effects. RESULTS: After gradually increasing cenobamate to clinical effect using the FDA-approved dosing protocol, 60% (n = 22) of patients were responders. Adolescents were treated with an average daily dose of 204.0 mg, and adults with 223.4 mg cenobamate, and had serum levels of 20.5 µg/mL and 26.7 µg/mL, respectively. The side effect profile observed was similar to that seen in the phase 2/3 registry trials. Importantly, patients with a prior history of rash to other medications or antiseizure medications (n = 5) experienced no rashes related to cenobamate. CONCLUSIONS: This real-world study supports the findings of prior controlled studies regarding the efficacy of cenobamate as a treatment for focal seizures in adolescents and suggests that patients with a history of rash may benefit from this medication.

Case Report: The Complexities of Managing Medications and the Importance of Deprescribing Anticholinergics in Older Adults.

Potentially inappropriate anticholinergic medications (including over-the-counter products), polypharmacy, and the existence of communication barriers among members of the interprofessional team frequently contribute to clinical complexity in older adults. We present the case of a frail 86-year old female from the perspective of a community pharmacist managing outpatient medications and transitions of care. CD's past medical history is significant for dementia, multiple falls, recurrent urinary tract infections, depression, cardiac arrhythmia, macular degeneration, chronic pain, depression, and cerebrovascular disease.

The role of fluid-phase immune complexes in the pathogenesis of heparin-induced thrombocytopenia.

Immune complexes assemble on the platelet surface and cause Fc-mediated platelet activation in heparin-induced thrombocytopenia (HIT); however, it is not known if fluid-phase immune complexes contribute to HIT. The objective of this study was to understand the role of fluid-phase immune complexes in platelet activation and HIT. Binding of wild-type and 15 platelet factor 4 (PF4) mutants to platelets was measured using flow cytometry. Platelet activation was measured using the PF4-dependent 14C-serotonin release assay (PF4-SRA) with KKO and a HIT-patient plasma in the presence of wild-type or PF4 mutants. To activate platelets, we found that a minimal level of wild-type PF4 is required to bind the platelet surface in the presence of KKO (2.67 relative MFI) or HIT-patient plasma (1.71 relative MFI). Only a subset of PF4 mutants was able to support platelet activation, despite having lower surface binding than the minimum binding required of wild-type PF4 (9 mutants with KKO and 2 mutants with HIT-patient plasma). Using individual PF4 mutants, we identified that HIT immune complexes can be formed in fluid-phase and induce platelet activation. Further studies are required to investigate the role of fluid-phase HIT immune complexes in the development of thrombocytopenia and thrombosis associated with clinical HIT.

Platelet factor 4 inhibits ADAMTS13 activity and regulates the multimeric distribution of von Willebrand factor.

The efficiency of von Willebrand factor (VWF) in thrombus formation is related to its multimeric size, which is controlled by the protease ADAMTS13. However, it is not clear what regulates ADAMTS13 activity. In this study, we investigated whether PF4 could bind to VWF and inhibit ADAMTS13 activity. We found that PF4 binds to VWF and protects against ADAMTS13 activity. We also found that VWF-PF4 complexes circulate in patients with thrombotic thrombocytopenic purpura (TTP). Our data provides the first evidence that PF4 may have a novel role in regulating VWF multimers during primary haemostasis and thrombosis.