CNS Aspergillosis and Cryptococcosis with Cytomegalovirus Pneumonia in a Patient with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.

Bruton's tyrosine kinase inhibitors (BTKis) are the preferred treatment for chronic lymphocytic leukemia (CLL). Despite their therapeutic benefits, these targeted agents have been associated with an increased risk of invasive infections. We describe a 68-year-old male who developed multiple bacterial, fungal and viral infections while on treatment with acalabrutinib. To our knowledge, this is the first reported case of concomitant CNS infections with Cryptococcus neoformans and Aspergillus fumigatus, along with cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) pneumonia while on acalabrutinib. This case adds to the scarce literature of fungal and bacterial infections associated with acalabrutinib, raising the suspicion that infection risk is a medication class effect for BTKis.

Pilot Evaluation of Generation Rx Ambassadors Virtual Training to Prepare Students for Medication Safety Outreach.

Objective. To describe the creation of a virtual training program (Generation Rx Ambassadors) and evaluate a pilot offering's impact on knowledge and perceived abilities in delivering medication safety outreach through the Generation Rx program.Methods. Generation Rx (GenRx) is a prevention education program used by student pharmacists to teach safe medication practices in the community. An asynchronous virtual course, called Generation Rx Ambassadors (Ambassadors), was developed to train facilitators on best practices for GenRx delivery. The training was piloted in a mixed student cohort and evaluated using a preprogram/postprogram survey assessing participants' objective knowledge gains and self-perceived abilities to appropriately deliver GenRx education.Results. Fifty-two health sciences undergraduate and graduate students as well as Doctor of Pharmacy (PharmD) students completed the pilot offering of Ambassadors. Regardless of degree status or discipline, participants demonstrated significant knowledge gains for all outcomes except defining medication misuse behaviors (for which there was initial strong mastery). Prior to Ambassadors training, many participants indicated a perceived ability to effectively deliver GenRx education; however, corresponding objective knowledge assessment did not support this belief. Training through the Ambassadors program appropriately aligned participants' perceived abilities with actual content knowledge for most program learning outcomes.Conclusion. These pilot findings suggest that Ambassadors is an effective training tool on best practices for GenRx delivery. More generally, this work reiterates a need to formally train student pharmacists ahead of community outreach activities, particularly in the prevention education arena. Future evaluation will focus on replicating this study with an expanded cohort size and assessing participants' ability to deliver GenRx education in community-based settings.

A second hit? Pulmonary arterial hypertension, BMPR2 mutation, and exposure to prescription amphetamines.

The second hit hypothesis in pulmonary hypertension refers to the development of pulmonary vascular disease in individuals at risk, after an additional exposure or "hit" to factors with potential injury to the pulmonary circulation, such as drugs or toxins. We here present a case of severe pulmonary hypertension diagnosed during the third trimester of pregnancy, in a patient with familial history of pulmonary hypertension, found to have a heterozygous mutation in the BMPR2 gene, who also had chronic exposure to prescription amphetamines. We hypothesize that exposure to prescription amphetamines could act as a second hit of pulmonary vascular injury in individuals at risk of pulmonary vascular disease.

Bleeding Risk of Therapeutic Unfractionated Heparin and Low Molecular Weight Heparin in Patients with Cirrhosis.

BACKGROUND AND OBJECTIVE: Patients with cirrhosis are simultaneously at an increased risk of bleeding and thrombosis. Studies comparing the safety of parenteral anticoagulants in this population are lacking. This study evaluated the safety of therapeutic unfractionated heparin versus low molecular weight heparin in patients with cirrhosis. METHODS: This system-wide, retrospective cohort study included adults with cirrhosis receiving unfractionated heparin or low molecular weight heparin for the treatment of acute venous thromboembolism. The primary endpoint was the incidence of major bleeding. RESULTS: Eighty-two patients were included in this study, with 52 receiving unfractionated heparin and 30 receiving low molecular weight heparin. More major bleeding occurred in the unfractionated heparin arm compared to the low molecular weight heparin arm (19.2% vs 0%, p = 0.010). CONCLUSIONS: Low molecular weight heparin may be a safer option in patients with cirrhosis treated for acute venous thromboembolism, but future studies should confirm these findings.

Extracellular dopamine kinetic parameters consistent with amphetamine effects.

Published behavioral experiments document that amphetamine-induced increases in locomotor activity are preserved or enhanced in animals with major depletions of stored dopamine but intact dopamine synthesis. Conversely, amphetamine effects are substantially attenuated after inhibition of dopamine synthesis when most of the dopamine stores are preserved. Such data suggest that amphetamine mobilizes newly synthesized dopamine into extracellular signaling space. The first goal of this project is to determine kinetic parameters of dopamine secretion into and removal from extracellular space compatible with the majority of amphetamine-elicited increases in extracellular dopamine deriving from newly synthesized dopamine. The strategy uses a computational model of extracellular space surrounding a single dopamine varicosity. Model output was compared to published micro-dialysis data for effects of amphetamine on levels of extracellular dopamine. A family of solutions was found, characterized by a biphasic dose-response relationship for rate of dopamine release. Maximum rates of dopamine release occurred at doses of 0.5-1.0 mg/kg amphetamine. The second goal is to develop a hypothesis by which newly synthesized dopamine gains access to extracellular space. The model chosen involves amphetamine-induced shunting of DOPAC secretion to dopamine secretion into extracellular space. The quality of the hypothesis was evaluated by goodness of match of model output to published data for amphetamine alone and after inhibition of dopamine synthesis or storage. In summary, the results provide conditions required for and a potential mechanism for newly synthesized dopamine to be a major fraction of amphetamine-elicited increases in extracellular dopamine.

Evaluation of Rescue Thrombolysis in Cardiac Arrest Secondary to Suspected or Confirmed Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) is the associated cause of unexplained cardiac arrest in 5% to 13% of patients. Although thrombolytic agents have been studied, patient outcomes during cardiac arrest are lacking. OBJECTIVE: The purpose of this study was to describe outcomes of patients who received thrombolytic therapy during cardiac arrest for suspected or confirmed PE. METHODS: This retrospective review included adults who received alteplase or tenecteplase during cardiac arrest for suspected or confirmed PE. The primary end point was incidence of survival to hospital discharge, whereas secondary end points included a description of dosing strategies of thrombolytic therapy, the incidence of return of spontaneous circulation (ROSC), the occurrence of minor or major bleeding, and intensive care unit and hospital lengths of stay. RESULTS: Of the 22 patients included in the study, 3 patients (13.6%) survived to hospital discharge, and ROSC was obtained in 11 patients (50%). Three patients had confirmed PE prior to cardiac arrest, with the remaining 19 patients having a documented suspicion for PE. The most frequent dosing strategy was alteplase 100 mg given via intravenous push (13 of 22 patients; 59%). One minor and no major bleeding events occurred. Conclusion and Relevance: Medical advances in PE management continue to evolve; yet the role of thrombolytic therapy in PE-related cardiac arrest remains unclear, with low overall rates of survival. These findings add to the relatively small body of evidence and highlight that optimal dosing remains unknown in this setting.

Predictors of calf cramping in rugby league.

Exercise-associated muscle cramps (EAMC) in the calf are common in rugby league. To date, the etiology and predictors of calf cramping are poorly understood. The aim of this study was to undertake a prospective investigation to identify predictors of calf cramping in rugby league players. Demographic and anthropometric data and calf cramp and injury history were collected in the preseason. Hydration status, number of games played, and calf cramps were recorded on game days. Male rugby league players (n = 103, mean age 18.8 ± 4.1 years) were classified as either EAMC (experienced at least 1 incident of calf cramps in the season) or no EAMC (no calf cramps). The following were investigated as possible predictors of EAMC using logistic regression modeling: competition level, age, ethnicity, playing position, history of cramping, precramping, low back pain, foot orthotic usage, foot posture, foot strike, muscle flexibility, calf girth, hydration status, and number of games played. Half the players, n = 52, experienced at least 1 incidence of calf cramping. Playing in a senior competition level (odds ratio: 0.21; 95% confidence interval: 0.06-0.75; p = 0.016), a history of calf cramping (10.85; 2.16-54.44; p = 0.004), and a history of low back pain resulting in missed field minutes (4.50, 1.37-14.79; p = 0.013) were found to predict EAMC. This study suggests that there is a high incidence of calf cramping in rugby league, especially at senior competition levels, and supports preseason screening in senior players to idetify those at risk of calf cramping and the development of possible preventative strategies.