Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists.

OBJECTIVE: Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC).Data Sources: PubMed and relevant congress abstracts were searched using the term "glasdegib". In addition, based on our experience with glasdegib, we considered treatment aspects of particular relevance to pharmacists and advanced practitioners.Data Summary: In a randomized phase II study, the combination of glasdegib plus LDAC demonstrated superior overall survival versus LDAC alone (hazard ratio 0.51, 80% confidence interval 0.39-0.67, p = 0.0004). The trial reported adverse events (AEs) of special relevance for older patients, such as hematologic events, gastrointestinal toxicity, and fatigue, as well as AEs associated with Hh-pathway inhibitors (alopecia, muscle spasms, dysgeusia). Educating patients about typical AEs can facilitate adherence as well as early AE identification and proactive management. For LDAC, which is a long-established therapy in AML, various stages of delivery need consideration, with attention to individual circumstances. Practical measures such as dispensing a longer supply can reduce the number of return clinic visits, providing a meaningful difference for many patients. CONCLUSIONS: Pharmacists and advanced practitioners play important roles in treatment with glasdegib plus LDAC. Ultimately, framing plans for treatment delivery within the individual circumstances of each patient may enable them to stay on therapy longer, giving them the greatest potential to achieve benefit.

Evaluation of the head and neck cancer patient population and the incidence of hospitalization at an academic medical center.

PURPOSE: Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. METHODS: We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center. Secondary objectives included describing the clinical and social factors associated with hospitalization. RESULTS: There were 109 patients with head and neck cancer included in the analysis. Of these patients, 38 (35%) were hospitalized. The factors that were significantly associated with hospitalization on univariable logistic regression were former alcohol abuse, being on a nonstandard of care chemotherapy regimen, and having a chemotherapy agent discontinued. On multivariable logistic regression, the factor that was significantly associated with hospitalization was having a chemotherapy agent discontinued. The most common reasons for hospitalization included shortness of breath/respiratory failure, fever/neutropenic fever, and infection. The most common new supportive care medications prescribed at discharge were stool softeners or laxatives and opioids. CONCLUSION: This study identified several factors which may be useful to identify patients as high risk for hospitalization and the next steps will be to determine and study the role of the pharmacist in preventing hospitalization of these patients. Further studies are needed to assess the impact of adding a pharmacist to the head and neck cancer multidisciplinary team.

Activation of the Aryl Hydrocarbon Receptor by 10-Cl-BBQ Prevents Insulitis and Effector T Cell Development Independently of Foxp3+ Regulatory T Cells in Nonobese Diabetic Mice.

Aryl hydrocarbon receptor (AhR) activation by high-affinity ligands mediates immunosuppression in association with increased regulatory T cells (Tregs), making this transcription factor an attractive therapeutic target for autoimmune diseases. We recently discovered 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ), a nanomolar affinity AhR ligand with immunosuppressive activity and favorable pharmacologic properties. In this study, we tested the consequences of AhR activation in the NOD model. Oral 10-Cl-BBQ treatment prevented islet infiltration without clinical toxicity, whereas AhR-deficient NOD mice were not protected. Suppression of insulitis was associated with an increased frequency, but not total number, of Foxp3(+) Tregs in the pancreas and pancreatic lymph nodes. The requirement for Foxp3(+) cells in AhR-induced suppression of insulitis was tested using NOD.Foxp3(DTR) mice, which show extensive islet infiltration upon treatment with diphtheria toxin. AhR activation prevented the development of insulitis caused by the depletion of Foxp3(+) cells, demonstrating that Foxp3(+) cells are not required for AhR-mediated suppression and furthermore that the AhR pathway is able to compensate for the absence of Foxp3(+) Tregs, countering current dogma. Concurrently, the development of disease-associated CD4(+)Nrp1(+)Foxp3(-)RORγt(+) cells was inhibited by AhR activation. Taken together, 10-Cl-BBQ is an effective, nontoxic AhR ligand for the intervention of immune-mediated diseases that functions independently of Foxp3(+) Tregs to suppress pathogenic T cell development.

Systemic effects of low-dose dopamine during administration of cytarabine.

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m2/dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Effects of the leucovorin shortage: Pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer.

Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200-500 mg/m2/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580-3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m2 or 400 mg/m2 dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.

A review of blinatumomab, a novel immunotherapy.

Blinatumomab is a novel bispecific CD19-directed CD3 T-cell engager recently approved for the treatment of relapsed or refractory Ph-negative acute lymphoblastic leukemia in adults. The drug was approved after a phase II trial in adults with relapsed/refractory disease demonstrated complete remission or hematologic complete remission in 43% of patients within two treatment cycles, of which 40% went on to receive an allogeneic hematopoietic stem cell transplant. In a long-term survival analysis of patients with minimal residual disease after chemotherapy, hematologic relapse-free survival was estimated at 61% at a median of 33 months after blinatumomab. Nine patients underwent hematopoietic stem cell transplant, and six patients remained in complete remission without hematopoietic stem cell transplant or further therapy. Limited data in relapsed pediatric acute lymphoblastic leukemia are reviewed. Blinatumomab carries boxed warnings for neurotoxicity and cytokine release syndrome, which may be serious and lead to treatment interruption and discontinuation. Clinical controversies with blinatumomab include use in patients with Ph-positive acute lymphoblastic leukemia, dosing in underweight adults, and the optimal management of cytokine release syndrome. Oncology pharmacists must be aware of detailed preparation and administration procedures required for safe use of blinatumomab. Clinical trials are ongoing in the first-line setting for patients with Ph-negative acute lymphoblastic leukemia, in Ph-positive acute lymphoblastic leukemia, and other B-cell malignancies.

A Fatal Case of Immune Checkpoint Inhibitor-Mediated Myasthenia Gravis, Myositis, and Cardiomyopathy Overlap Syndrome in Urothelial Carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to improved outcomes for many cancer types. However, their use can also precipitate immune-related adverse events (irAEs) that can affect any organ system. While irAEs are often mild, they rarely affect multiple organ systems concurrently and can be fatal. CASE: We report a fatal case of myasthenia gravis, myositis, and cardiotoxicity overlap syndrome precipitated by the ICI pembrolizumab along with a brief review of available literature. CONCLUSION: Early recognition of high grade irAEs and prompt intervention is essential. Despite the poor prognosis of these overlap syndromes, current recommendations offer little guidance for severe cases and warrant a call for increased awareness and expansion of available therapeutics.

Impact of Prophylactic Trimethoprim-Sulfamethoxazole on Clearance of High-Dose Methotrexate in Adult Patients.

PURPOSE: High-dose methotrexate (HDMTX) is an antineoplastic dosing strategy used to treat various cancers including primary central nervous system lymphoma. Trimethoprim-sulfamethoxazole (TMP/SMX) is commonly used for antibiotic prophylaxis against Pneumocystis pneumonia infections in this patient population. Significant drug-drug interactions between TMP/SMX and methotrexate (MTX) leading to adverse outcomes have been documented, primarily in adult patients taking MTX for rheumatologic conditions. METHODS: This study is a single-center, retrospective, cohort study comparing outcomes in patients where TMP/SMX was held during HDMTX and patients who received concurrent prophylactic TMP/SMX during treatment. The primary end point was mean MTX level at 24, 48, and 72 hours. Secondary end points included rate of nonhematologic toxicity, rate of hematologic toxicity, median days to MTX clearance, and frequency of glucarpidase utilization. RESULTS: In total, 248 cycles of HDMTX were analyzed from 221 individual patients. One hundred ninety-one cycles were administered without prophylactic TMP/SMX, and 57 were administered with TMP/SMX. The median MTX level at 24, 48, and 72 hours in those without versus with prophylactic TMP/SMX was 4.30 versus 4.30, 0.29 versus 0.30, and 0.14 versus 0.15, respectively. Similarly, rates of hematologic and nonhematologic toxicities did not differ significantly between groups with the exception of neutropenia; however, there was no corresponding increased rate of neutropenic fever. Only one patient received glucarpidase and had not received TMP/SMX. CONCLUSION: Prophylactic TMP/SMX had minimal interaction with HDMTX and does not lead to increased time to clearance or clinically relevant toxicities. Prophylactic TMP/SMX can be safely administered with HDMTX in adult patients.

Fit2Drive: Screening Older Drivers with Cognitive Concerns.

OBJECTIVES: The purpose of this study was to identify the most parsimonious combination of cognitive tests that accurately predicts the likelihood of passing an on-road driving evaluation in order to develop a screening measure that can be administered as an in-office test. DESIGN: This was a psychometric study of the new test's diagnostic accuracy. SETTINGS AND PARTICIPANTS: The study was conducted at the Florida Atlantic University's Memory Center and Clinical Research Unit, both easily accessible to older drivers. Participants were older drivers who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository and community-based older drivers who volunteered to participate. METHODS: Mini-Mental State Exam (MMSE), Trail Making Tests A and B, Clock Test, Hopkins Verbal Learning Test, and Driving Health Inventory results were compared with an on-road driving evaluation to identify those tests that best predict the ability to pass the on-road evaluation. RESULTS: Altogether, 412 older drivers, 179 men and 233 women, were included in the analysis. Fifty-four percent of Driving Repository participants failed the on-road evaluation compared with 8% of the community sample. The highest correlation to the on-road evaluation was Trails B time in seconds r = -0.713 (P < .001). Variables with high multicollinearity and/or low correlation with the on-road evaluation were eliminated and sets of receiver operating characteristics curves were generated to assess the predictive accuracy of the remaining tests. A linear combination of Trails B in seconds and MMSE using the highest of the Serial 7s or WORLD spelled backward scores accounted for the highest area under the curve of 0.915. Finally, an algorithm was created to rapidly generate the prediction for an individual patient. CONCLUSIONS AND IMPLICATIONS: The Fit2Drive algorithm demonstrated a strong 91.5% predictive accuracy. Usefulness in office-based patient consultations is promising but remains to be rigorously tested.

Early-onset juvenile nasopharyngeal angiofibroma (JNA): a systematic review.

BACKGROUND: Juvenile Nasopharyngeal Angiofibroma (JNA) is a fibrovascular tumor of the nasopharynx that classically presents in adolescent males. The reported mean age of onset is between 13 and 22 years old [1-6]. Significant androgen stimulation is hypothesized to explain the strong predisposition for JNA to present in young adolescent males. However, considerable variability in age at diagnosis exists with rare involvement of very young patients incongruent with typical male pubertal growth patterns. OBJECTIVE: The purpose of this systematic review is to identify cases of early-onset JNA (EOJNA), (defined as age < 10 years) in the literature and to examine the disease characteristics and treatments used in this patient group. A case of a 7 year old boy with EOJNA at our institution is also described and presented. METHODS: We searched Embase, Cochrane database and MEDLINE from 1996 to February 2021 for studies that reported cases of EOJNA. Relevant clinico-demographic data, disease severity and treatment outcomes were recorded and analyzed using descriptive statistics. We compared our findings with reported means for JNA in all ages. RESULTS: We identified 29 studies containing a total of 34 cases of EOJNA. The vast majority (31/34) of patients were males and the mean age of diagnosis was 8.15 years old. The most common presenting symptoms were nasal obstruction (65.2%) and epistaxis (60.9%). Patients were most commonly Radkowski stage II (39.4%) and III (39.4%). Primary treatment modalities included open surgery (66.7%), endoscopic surgery (24.2%), and radiotherapy (9.1%). Recurrence was evident in 30%. Radkowski stage and type of treatment did not differ significantly within the EOJNA group (p = 0.440 and p = 0.659, respectively). CONCLUSION: This systematic review suggests that rare cases of EOJNA have distinct disease characteristics. Patients in this cohort appeared to have more advanced disease and higher recurrence rates when compared with reported averages. We hope that this review prompts increased clinical awareness of this potentially more aggressive subtype of JNA. As more cases of EOJNA are reported, a more powered statistical analysis of this cohort would be feasible.

BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8+ T cells.

Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8+ T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8+ T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor-exhausted T cells. This reversal was enhanced by combined BETi and anti-PD1 treatment. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increase in expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8+ T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8+ T cells and maintaining a pool of anti-PD1 responsive CD8+ T cells.

Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease.

The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups.

Impact of a national propofol shortage on duration of mechanical ventilation at an academic medical center.

OBJECTIVE: To measure the impact of a national propofol shortage on the duration of mechanical ventilation. DESIGN: Before-after study. SETTING: Three, noncardiac surgery, adult intensive care units at a 320-bed academic medical center. PATIENTS: Consecutive patients requiring mechanical ventilation ≥48 hrs, administered a continuously infused sedative ≥24 hrs, extubated, and successfully discharged from the intensive care unit were compared between before (December 1, 2008 to May 31, 2009) and after (December 1, 2009, to May 31, 2010) a propofol shortage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sedation drug use and common factors affecting time on mechanical ventilation were collected and if found either to differ significantly (p ≤ .10) between the two groups or to have an unadjusted significant association (p ≤ .10) with time on mechanical ventilation were included in a multivariable model. The unadjusted analyses revealed that the median (interquartile range) duration of mechanical ventilation increased from 6.7 (9.8; n = 153) to 9.6 (9.5; n = 128) days (p = .02). Fewer after-group patients received ≥24 hrs of continuously infused propofol (94% vs. 15%, p < .0001); more received ≥24 hrs of continuously infused lorazepam (7% vs. 15%, p = .037) and midazolam (30% vs. 81%, p < .0001). Compared with the before group, the after group was younger, had a higher admission Acute Physiology and Chronic Health Evaluation II score, was more likely to be admitted by a surgical service, have acute alcohol withdrawal, and be managed with pressure-controlled ventilation as the primary mode of mechanical ventilation. Of these five factors, only the Acute Physiology and Chronic Health Evaluation II score, admission service, and use of a pressure-controlled ventilation affected duration of mechanical ventilation across both groups. Although a regression model revealed that Acute Physiology and Chronic Health Evaluation II score (p < .0001), admission by a medical service (p = .009), and use of pressure-controlled ventilation (p = .02) each affected duration of mechanical ventilation in both groups, inclusion in either the before- or after-propofol shortage groups (i.e., high vs. low use of propofol) did not affect duration of mechanical ventilation (p = .35). CONCLUSIONS: An 84% decrease in propofol use in the adult intensive care units at our academic institution as a result of a national shortage did not affect duration of mechanical ventilation.

FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution.

MOTIVATION: Next generation sequencing technology generates high-throughput data, which allows us to detect fusion genes at both transcript and genomic levels. To detect fusion genes, the current bioinformatics tools heavily rely on paired-end approaches and overlook the importance of reads that span fusion junctions. Thus there is a need to develop an efficient aligner to detect fusion events by accurate mapping of these junction-spanning single reads, particularly when the read gets longer with the improvement in sequencing technology. RESULTS: We present a novel method, FusionMap, which aligns fusion reads directly to the genome without prior knowledge of potential fusion regions. FusionMap can detect fusion events in both single- and paired-end datasets from either RNA-Seq or gDNA-Seq studies and characterize fusion junctions at base-pair resolution. We showed that FusionMap achieved high sensitivity and specificity in fusion detection on two simulated RNA-Seq datasets, which contained 75 nt paired-end reads. FusionMap achieved substantially higher sensitivity and specificity than the paired-end approach when the inner distance between read pairs was small. Using FusionMap to characterize fusion genes in K562 chronic myeloid leukemia cell line, we further demonstrated its accuracy in fusion detection in both single-end RNA-Seq and gDNA-Seq datasets. These combined results show that FusionMap provides an accurate and systematic solution to detecting fusion events through junction-spanning reads. AVAILABILITY: FusionMap includes reference indexing, read filtering, fusion alignment and reporting in one package. The software is free for noncommercial use at (http://www.omicsoft.com/fusionmap).

Cost-effectiveness of fulvestrant 250 mg versus 500 mg in postmenopausal women with estrogen receptor-positive metastatic breast cancer and disease progression after antiestrogen therapy.

PURPOSE: To determine the cost-effectiveness of fulvestrant 250 mg compared to 500 mg in postmenopausal women with estrogen receptor-positive metastatic breast cancer and disease progression after antiestrogen therapy. METHODS: A Markov model was constructed to find the incremental cost-effectiveness of fulvestrant 250 mg monthly when compared with the 500 mg monthly in patients with progression after antiestrogen therapy. The model duration was 24 months. Clinical efficacy data inputs were derived from a phase III clinical trial demonstrating a statistically significant increase in progression-free survival in patients receiving 500 mg versus 250 mg. Cost data utilized were all relevant Ambulatory Payment Classification payment rates from the 2011 Medicare Outpatient Prospective Payment System. A Monte Carlo simulation was performed to test the model at various willingness to pay thresholds. RESULTS: The incremental cost-effectiveness ratio as determined by the Markov model was US$10,972 per month of progression-free survival for the 500 mg dose compared with the 250 mg dose. Using a Monte Carlo simulation, it was found that 500 mg monthly was cost-effective at and above the willingness to pay threshold of US$15,000 per month. A series of one-way sensitivity analyses showed this result is robust to geographical practice variations in costs of drug administration and physician examination. CONCLUSION: From a third party payer perspective, the value of fulvestrant 500 mg monthly is dependent on the willingness to pay threshold. Despite a labeling change for fulvestrant in September 2010, fulvestrant 250 mg monthly appears to be a viable option in the target population.

Pseudo-Renal Failure in the Context of Traumatic Bladder Rupture.

The bladder is both an intraperitoneal and extraperitoneal structure. Its anatomical position increases its risk of rupture. The resultant urine leak or extravasation can be intraperitoneal, extraperitoneal, or even both-with the former leading to more sinister outcomes. Intraperitoneal bladder rupture can lead to urinary ascites which along with anuria and abdominal pain, can present with an apparent abrupt decline in renal function as the creatinine-rich products diffuse across the peritoneal membrane. Glomerular filtration rate, a measure of kidney function is related to the levels of serum creatinine. Clinicians can therefore misdiagnose their patient with acute kidney injury when the serum creatinine is elevated as a consequence of urine being present in the peritoneal space.  This is a case report of a 62-year-old male with pseudo-renal failure following intraperitoneal bladder rupture after a fall face-forwards three hours previously. The fall was due to icy conditions outside and no preceding symptoms were reported. He presented to the Accident and Emergency department with abdominal pain and no other positive symptoms. The patient had a good World Health Organisation (WHO) performance status with a background of hypertension, diabetes, and hypercholesterolemia. The bedside examination of the patient revealed a distended, abdomen with peritonitis. There were no signs of urogenital trauma. Blood testing revealed a low estimated glomerular filtration rate (eGFR) and raised creatinine (eGFR of 7 millilitres/minute and creatinine of 658 micromoles/litre). Computerised tomography examination of the abdomen and pelvis (CTAP) revealed free fluid within the peritoneal cavity and an irregular bladder wall. A CT cystogram and consultation with urology led to the diagnosis of intraperitoneal bladder rupture. The patient's renal function from an initial set of blood tests was reduced. This was not a true impairment in renal function but rather a complication secondary to extravasation of urine in the intraperitoneal space, ie., pseudo renal failure. This supposed impairment in renal function had numerous implications. It affected the choice of antibiotics; amoxicillin and gentamicin were given at a reduced dose due to the patient's renal function and the patient was prepared for operation theatre. The patient's blood creatinine was falsely elevated at 658 micromoles/litre due to the diffusion of creatinine from the free urine in the peritoneal space into the blood. This painted a false image of renal failure and protracted the clinical decision-making process. Relatively simple measures like an ascitic tap could have helped to differentiate this from a true acute kidney injury and could have resulted in quicker and more effective treatment of this patient.  The patient went on to have bladder repair under urology. His follow-up cystogram four weeks post-operation did not show any leak.

Establishing the Content Validity of a Student Pharmacist Patient Counseling Competency Assessment in Oncology.

Objective. The goal of this project was to establish content validity and describe internal consistency of a patient counseling competency assessment instrument used to evaluate student pharmacists practicing in an oncology setting.Methods. The study involved a modified e-Delphi panel of oncology clinical pharmacy specialists, clinical pharmacy generalists, and oncology pharmacy residents. Iterative rounds of the e-Delphi process were conducted until consensus was reached on most instrument items. Consensus was defined as agreement by at least 75% of participants that an item was or was not important.Results. The modified e-Delphi process included three rounds of responses from 13 panelists and resulted in a 35-item instrument with consensus reached on 33/35 (94%) of the items. All participants indicated that the assessment result options allowed them to indicate the student's level of competency either extremely well or very well.Conclusion. A modified e-Delphi method was used to validate a reliable instrument for the assessment of student pharmacist counseling abilities in an oncology setting. Similar methodology should be considered during the development of student assessment tools, especially for high-impact student pharmacist activities such as chemotherapeutic medication counseling.

Arsenic trioxide for acute promyelocytic leukemia in a patient on chronic hemodialysis.

Acute promyelocytic leukemia (APL) is a rare acute leukemia generally considered curable with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Some patients have co-morbidities that may limit the use of these agents and therefore impact curability. Adverse effects of ATO include life-threatening electrocardiographic abnormalities. ATO and its metabolites are partially excreted in the urine, and it is unclear to what extent ATO pharmacokinetics are impacted by hemodialysis. We present a patient on chronic hemodialysis successfully treated with ATO and ATRA for newly diagnosed APL. Complete molecular remission was achieved after induction and several drug-related toxicities were managed.