An examination of nurse practitioner students' perceptions of knowledge, confidence, and experiences related to caring for lesbian, gay, bisexual, transgender, and queer or questioning patients: A national perspective.

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ+) individuals are significantly less likely to have a primary health care provider, be uninsured, and postpone medical care. A health care provider's lack of knowledge in LGBTQ+ health needs, low confidence in discussing sexuality, and bias can result in LGBTQ+ patients choosing to delay or avoid seeking care. These are missed opportunities for health care providers to recognize their unique needs, provide education and preventive screenings and care, and manage chronic conditions. PURPOSE: The aim of this study was to examine nurse practitioner students' perceptions of knowledge, confidence, and experiences related to caring for LGBTQ+ patients. METHODOLOGY: Using a descriptive, cross-sectional survey research design, a 29-item online survey was distributed through email to nurse practitioner students (n = 419) across the United States. RESULTS: Overall, nurse practitioners (NP) students demonstrated infrequent questioning related to gender preferences, sexual terms, and clarification of relationships. Results showed that 77.9% of NP students within two terms of graduation had not received any LGBTQ+-specific training. Almost 75% of the NP students reported not routinely asking about sexuality, and 82% reported infrequently or never asking gender identity. Furthermore, 93.1% of respondents reported providers infrequently or never ask about preferred gender or pronouns, and 86% reported providers infrequently inquire about sexual identity in primary care visits. CONCLUSIONS: Study findings demonstrate the uniqueness of managing care for LGBTQ+ patients and importance for more detailed LGBTQ+ health training in curricula in NP programs. IMPLICATIONS: Closing the gap in health care for LGBTQ+ patients is paramount in addressing global health disparities and population care.

Low-risk relapsed acute lymphoblastic leukemia in children and young adults: what have we learnt and what's next?

While outcomes for newly diagnosed children with acute lymphoblastic leukemia (ALL) have improved over the last few decades, 10-15% will relapse. Outcomes for those children with relapse remains a challenge, with 5-year overall survival of approximately 35-60%. Large cooperative group trials have identified factors associated with favorable (low risk, LR) outcome at relapse, including later relapse, B-cell phenotype, isolated extramedullary relapse and a good response to initial re-induction therapy. Contemporary therapeutic regimens are aimed at improving outcomes, while decreasing toxicity. A main focus of current research involves how immunotherapy can be best incorporated with cytotoxic chemotherapy to improve survival in relapsed ALL. Here we review therapeutic strategies for LR relapse, including review of recently completed and ongoing trials.

Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921.

PURPOSE: Bosutinib is approved for adults with chronic myeloid leukemia (CML): 400 mg once daily in newly diagnosed (ND); 500 mg once daily in resistant/intolerant (R/I) patients. Bosutinib has a different tolerability profile than other tyrosine kinase inhibitors (TKIs) and potentially less impact on growth (preclinical data). The primary objective of this first-in-child trial was to determine the recommended phase II dose (RP2D) for pediatric R/I and ND patients. PATIENTS AND METHODS: In the phase I part of this international, open-label trial (ClinicalTrials.gov identifier: NCT04258943), children age 1-18 years with R/I (per European LeukemiaNet 2013) Ph+ CML were enrolled using a 6 + 4 design, testing 300, 350, and 400 mg/m2 once daily with food. The RP2D was the dose resulting in 0/6 or 1/10 dose-limiting toxicities (DLTs) during the first cycle and achieving adult target AUC levels for the respective indication. As ND participants were only enrolled in phase II, the ND RP2D was selected based on data from R/I patients. RESULTS: Thirty patients were enrolled; 27 were evaluable for DLT: six at 300 mg/m2, 11 at 350 mg/m2 (one DLT), and 10 at 400 mg/m2 (one DLT). The mean AUCs at 300 mg/m2, 350 mg/m2, and 400 mg/m2 were 2.20 µg h/mL, 2.52 µg h/mL, and 2.66 µg h/mL, respectively. The most common adverse event was diarrhea (93%; ≥grade 3: 11%). Seven patients stopped because of intolerance and eight because of insufficient response. Complete cytogenetic and major molecular response to bosutinib appeared comparable with other published phase I/II trials with second-generation TKIs in children. CONCLUSION: Bosutinib was safe and effective. The pediatric RP2D was 400 mg/m2 once daily (max 600 mg/d) with food in R/I patients and 300 mg/m2 once daily (max 500 mg/d) with food in ND patients, which achieved targeted exposures as per adult experience.

Tisagenlecleucel utilisation and outcomes across refractory, first relapse and multiply relapsed B-cell acute lymphoblastic leukemia: a retrospective analysis of real-world patterns.

Background: Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval. Methods: We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts. Findings: Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74-92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58-82%) and 49%, (95% CI 37-64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58-90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory. Interpretation: Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease. Funding: St. Baldrick's/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.

Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

PURPOSE: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy. EXPERIMENTAL DESIGN: We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients. We identified a novel mutation in PDGFRA, p.D842N, and used an integrated structural modeling and molecular biology approach to characterize mutations at D842 to guide therapeutic targeting. We conducted a preclinical study of avapritinib in a mouse patient-derived xenograft (PDX) model of FIP1L1-PDGFRA and PDGFRA p.D842N leukemia. RESULTS: Two patients with T-ALL in the LEAP cohort (14%) had targetable genomic alterations affecting PDGFRA, a FIP1-like 1 protein/PDGFRA (FIP1L1-PDGFRA) fusion and a novel mutation in PDGFRA, p.D842N. The D842N mutation resulted in PDGFRA activation and sensitivity to tested PDGFRA inhibitors. In a T-ALL PDX model, avapritinib treatment led to decreased leukemia burden, significantly prolonged survival, and even cured a subset of mice. Avapritinib treatment was well tolerated and yielded clinical benefit in a patient with refractory T-ALL. CONCLUSIONS: Refractory T-ALL has not been fully characterized. Alterations in PDGFRA or other targetable kinases may inform therapy for patients with refractory T-ALL who otherwise have limited treatment options. Clinical genomic profiling, in real time, is needed for fully informed therapeutic decision making.

Bronchiolitis Simulation Module in the Pediatric Preclerkship Educational Exercises (PRECEDE) Curriculum.

Introduction: Acute bronchiolitis is a viral infection infecting 90% of children under the age of 2 years, with approximately 200,000 deaths per year. The current standard of care remains largely respiratory support and prevention. Therefore, understanding how to assess and escalate respiratory supportive care is paramount for health care providers taking care of children. Methods: We used a high-fidelity simulator to simulate an infant with progressing respiratory distress in the setting of acute bronchiolitis. The participants were pediatric clerkship medical students during their preclerkship educational exercises (PRECEDE). The students were asked to evaluate and treat the simulated patient. After debriefing, the students repeated the simulation. We assessed both performances via a weighted checklist specifically developed for this case to measure team performance. Students also completed an overall course evaluation. Results: Ninety out of 121 pediatric clerkship students were enrolled. Performance improved from 57% to 86% ( p < .05). Donning appropriate personal protection equipment was the most missed item both pre- and postdebriefing. Overall, the course was well liked and received. Participants requested more simulation opportunities within PRECEDE as well as a summary document to reinforce learning. Discussion: Pediatric clerkship students improved their performance managing progressing respiratory distress due to acute bronchiolitis via a performance-based assessment tool with sound validity evidence. Improvements going forward include improving faculty diversity and offering more simulation opportunities.

SOHO State of the Art Updates and Next Questions | Optimal Timing of Blinatumomab for the Treatment of B-Acute Lymphoblastic Leukemia.

Blinatumomab is a CD19 targeting bi-specific T-cell engager antibody construct developed for the treatment of CD19 expressing B-cell malignancies. Numerous adult and pediatric B-ALL clinical trials have demonstrated blinatumomab's efficacy in the relapse setting as well as in patients with residual disease after upfront chemotherapy. The safety profile of blinatumomab is also favorable, making it a feasible option for most patients. Several key questions remain, including the role of blinatumomab as a replacement for toxic elements of standard chemotherapy regimens in the upfront setting, its role as a bridge to hematopoietic stem cell transplantation, or whether previous blinatumomab impacts the efficacy of subsequent CAR-T cell therapy.

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults.

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.

Addressing Schooling in Children With Cancer-It's Everybody's Job, So It's Nobody's Job: An Explanatory Mixed-Methods Evaluation.

Background: Neurocognitive deficits from childhood cancer treatment are common, long-standing, and negatively impact multiple domains of life leading to challenges with schooling and education. The purpose of this study is to describe caregiver-reported experiences of neurocognitive effects from therapy and to understand the roles clinicians play in this domain in the United States. Methods: An explanatory mixed-methods study of 174 caregivers of children with cancer provided insight into how clinicians provided information on neurocognitive effects of treatment and their experiences with school-related resources. Clinicians provided descriptions of how they provide this information and assist families with accessing services or transition back to school after therapy. Results: Caregivers identified that physicians, nurses, and social workers primarily provide information regarding neurocognitive effects of treatment. Over half (55.9%) of families seek additional information elsewhere and 49.4% report doing so because the information they received from their team was inadequate. Nearly 40% of caregivers report accessing school supports feels like a constant fight and over 40% were not offered homebound educational services by their school. Qualitative interviews with providers found that clinicians focus on therapy-related physical symptoms of treatment and only discuss neurocognitive effects when prompted by families or when children are returning to school. Discussion: Clinicians' focus on physical symptoms and just-in-time thinking when it comes to providing education or school-related services may explain why families endorse infrequent education on the topic and challenges with school reintegration. Improved education for clinicians on this topic, integration of interdisciplinary teams, and new clinical practice models may improve the family experience.

Trainee-led Engagement of the Care Team Improves Application of an Institutional Blood Culture Clinical Decision Algorithm to Pediatric Oncology Inpatients: A Single-institution Quality Improvement Project.

Meaningful engagement in quality improvement (QI) projects by trainees is often challenging. A fellow-led QI project aimed to improve adherence to a blood culture clinical decision algorithm and reduce unnecessary cultures in pediatric oncology inpatients. Methods: We visualized preintervention rates of blood cultures drawn on pediatric oncology inpatients using a control chart. Following the introduction of the algorithm to our division, an Ishikawa fishbone diagram of cause-and-effect identified two areas for improvement: prescriber education on the algorithm and targeted feedback on its use. We developed two interventions to support algorithm awareness and use: (1) bundled educational interventions and (2) targeted chart review and feedback. Fellows reviewed >750 blood culture episodes and adjudicated each as "adherent" or "nonadherent" to the algorithm. In addition, fellows provided direct feedback to prescribers regarding nonadherent episodes and discussed strategies for algorithm adherence. Results: Blood culture rates in preintervention, intervention, and follow-up periods were 33.35, 25.24, and 22.67 cultures/100 patient-days, respectively. The proportion of nonadherent culture episodes decreased from 47.14% to 11.11%. The use of the algorithm did not prolong the time to cultures drawn on patients with new fever. Seventy-five percent of fellows provided feedback to inpatient teams on algorithm use. Following this project, trainees reported feeling more qualified to apply QI principles to patient care. Conclusions: Implementation of a clinical decision algorithm reduced the rate of cultures drawn on pediatric oncology inpatients. Fellow-led education of the care team decreased the proportion of nonadherent culture episodes and provided active engagement in QI.

Considerations in Methods and Timing for Delivery of Genetic Counseling Information to Pediatric Oncology Patients and Families.

Many pediatric oncology patients and their families may benefit from genetic counseling and testing; however, identifying the best timing and delivery method for these referrals is sometimes a challenge. The goal of this study was to understand how and when caregivers prefer to receive information about genetic counseling and testing. A total of 56 surveys completed by caregivers at The Johns Hopkins Hospital Pediatric Oncology unit in Baltimore, Maryland were analyzed. A sizeable subset of respondents was interested in receiving information about the availability of genetic counseling from an oncology doctor or nurse, but not a genetic counselor (n=13/55, 24%). Most respondents preferred to be informed about genetic services at diagnosis (n=28/54, 52%) or within 1 to 2 months of diagnosis (n=14/54, 26%). In conclusion, patients and their families may benefit from prompt and early recognition of the risk of cancer predisposition syndromes, preferably within the first 2 months following diagnosis. Oncology professionals are an important source of information, and can introduce the availability of genetic counseling services and motivate families to undergo genetic testing, though alternative communication methods such as brochures may also be useful.

The "Day Zero Talk": the Initial Communication of a Pediatric Oncology Diagnosis by Primary Care Physicians and Other Primary Care Providers.

While much is known about the initial communication of a definitive pediatric cancer diagnosis by the child's pediatric oncologist, little is known about the discussions leading up to this formal conversation, which are often had with nononcologists. We sought to describe these initial conversations regarding the possibility of a child's oncologic diagnosis, from the perspective of both the patient/family as well as the provider. Semistructured interviews were performed with individuals involved with a child with recently diagnosed cancer at a quaternary care institution in an urban, mid-Atlantic city. Interviews were recorded, transcribed, and analyzed using qualitative thematic analysis. In total, 71 people were interviewed, representing the experiences of 29 unique pediatric patients. Patient and caregiver themes included recognition of the urgency of the situation and variety of terms used to indicate the potential of cancer. Physician themes included the impact of health literacy on the discussion and varying opinions on how direct to be regarding the possibility of a cancer diagnosis. The initial discussions of the possibility of a pediatric cancer diagnosis often occur with nononcologists, and this day zero talk is critical in laying the groundwork for future communication with providers.

Pediatric Hodgkin Lymphoma, Version 3.2021.

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

Investigational treatment options in phase I and phase II trials for relapsed or refractory acute lymphoblastic leukemia in pediatric patients.

Introduction: Upfront treatment of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) results in cure rates of 60-95%, depending on risk factors. However, patients with refractory or relapsed B-ALL or T-ALL have much worse outcomes with conventional chemotherapy, hence treatment of these cohorts with novel agents is a priority.Areas Covered: This paper reviews early phase clinical trials in pediatric leukemia. Investigational antibody therapy, chimeric antigen receptor T-cell (CAR-T), and other targeted therapies are examined. The authors discuss the mechanisms of action, side effects, trial designs, and outcomes and reflect on potential research directions. PubMed and Clinicaltrials.gov were searched from 2010 to present, using keywords 'lymphoblastic leukemia' with filters for pediatric age, Phase 1 clinical trial and Phase 2 clinical trial.Expert Opinion: Pediatric patients with relapsed or refractory leukemia often do not derive additional benefit from intensified conventional chemotherapy approaches which have arguably been maximized in the upfront setting. Therefore, novel approaches, such as immunotherapy and targeted agents should be prioritized. Progress will require commitment from pharmaceutical companies regarding these orphan diagnoses and acknowledgment from regulatory bodies that outcomes are suboptimal with conventional chemotherapy.

Improving Detection of Cancer Predisposition Syndromes in Pediatric Oncology.

Implementation and adherence to consensus statement criteria for referral of pediatric cancer patients for genetic evaluation are critical to identify the 5% to 10% with a genetic cancer predisposition syndrome. The authors implemented a Plan-Do-Study-Act quality improvement initiative aimed at increasing referrals of at-risk patients. Retrospective chart review was followed by educational intervention-with impact assessed over a 9-month prospective chart review. Referral rate improved >2-fold and there was an improvement in documented oncologic history to at least a third-degree relative. The integration of quality improvement can be an effective tool to improve the referral of patients with an elevated risk for a cancer predisposition syndrome.

Intrathecal chemotherapy-associated cerebral vasospasm in children with hematologic malignancies.

BACKGROUND: Mechanisms of chemotherapy-associated neurotoxicity are poorly understood, and therefore, prevention strategies have not been developed. We hypothesized that a subgroup of children receiving intrathecal cytarabine develops subclinical vasospasm, which may contribute to long-term neurocognitive sequelae of cancer. METHODS: We used transcranial Doppler ultrasound to serially evaluate cerebral blood flow velocities in participants ≤25 years old receiving intrathecal cytarabine for hematologic malignancies. RESULTS: Four of 18 participants (22%) met the criteria for subclinical vasospasm within 4 days of intrathecal cytarabine administration. The distribution of oncologic diagnoses differed between the vasospasm and non-vasospasm groups (p = 0.02). Acute myeloid leukemia was identified as a potential risk factor for vasospasm. Children with vasospasm were more likely to have received intravenous cytarabine (75% versus 0%, p = 0.01) and less likely to have received steroids (25% versus 100%, p = 0.01). CONCLUSIONS: A subpopulation of children with hematologic malignancies develops subclinical vasospasm after intrathecal cytarabine treatment. Future research is needed to determine the long-term clinical consequences of cerebral vasospasm in this population. IMPACT: A subset of children with hematologic malignancies who receive intrathecal cytarabine experience subclinical cerebral vasospasm, as measured by transcranial Doppler ultrasound. Of children receiving intrathecal cytarabine, those who develop cerebral vasospasm are more likely to have diagnosis of acute myeloid leukemia, more likely to receive concurrent intravenous cytarabine, and less likely to receive steroids as part of their chemotherapy regimen, as compared with children without vasospasm. Future research is needed to determine if vasospasm during chemotherapy is associated with higher rates of neurocognitive dysfunction, and if so, to focus on prevention of these long-term sequelae of childhood cancer.

Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity.

BACKGROUND: Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP. METHODS: Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy. RESULTS: From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004). CONCLUSIONS: Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression.

Use of Allopurinol to Mitigate 6-Mercaptopurine Associated Gastrointestinal Toxicity in Acute Lymphoblastic Leukemia.

An essential component of acute lymphoblastic leukemia (ALL) therapy is the prolonged maintenance phase with daily 6-mercaptopurine (6-MP) as the cornerstone. While 6-MP is generally well-tolerated, some patients suffer from significant side effects such as gastrointestinal (GI) toxicity, including hepatitis, hypoglycemia, nausea, and pancreatitis, which can substantially limit the tolerated dose of 6-MP. These toxicities are thought to result from skewed metabolism of 6-MP leading to an accumulation of the 6-methylmercaptopurine (6-MMP) metabolite. Here, we describe current knowledge behind the use of allopurinol to modify 6-MP metabolism and improve tolerance to therapy. This method has been successfully used in adults with inflammatory bowel disease refractory to purine therapy and has been modified for use in children with GI toxicities related to 6-MP in maintenance therapy for ALL. Use of allopurinol for 6-MP related toxicities should be reserved for patients in which an alternative cause of signs or symptoms has been excluded and for whom non-pharmacologic measures have failed. When allopurinol is used, simultaneous dose reduction of 6-MP is required to avoid severe myelosuppression and related side effects, though overall combination therapy appears to be well-tolerated and effective when instituted appropriately.

Otitis Media Module in the Pediatric Preclerkship Educational Exercises (PRECEDE) Curriculum.

Introduction: The Johns Hopkins Pediatrics Clerkship developed the PRECEDE (preclerkship educational exercises) curriculum with the primary goal of offering students formative instruction in essential pediatric clinical skills to prepare them for their clerkship. PRECEDE sessions occur at the beginning of each basic clerkship for new clinical clerkship students. The otitis media module is one in a series of modules presented in the curriculum and consists of a lecture and four short skills-development stations, each with a faculty facilitator. Methods: This 2-hour module began with a 1-hour didactic overview of otitis media. Medical students were divided into three groups. One group learned about writing prescriptions via two otitis media clinical vignettes. Another group explored visualization and diagnosis of otitis media via video. The last student group was subdivided and learned proper techniques for positioning and restraining pediatric patients during otoscopic exams and the psychomotor skills for performing otoscopic examinations, including pneumatic otoscopy. Student groups rotated through all four activity stations. Students were guided through discussion to develop interpretation, diagnostic, and treatment skills for acute otitis media. Results: Between 2010 and 2012, 254 third- and fourth-year medical students participated in this module. When asked to evaluate overall quality, 86% of learners rated the module as excellent, and 14% rated it as good. Discussion: By establishing these important skills, students may be better equipped to develop appropriate otitis media assessments, diagnoses, and care plans for patients and to use otitis media as a platform for broad education in other essential pediatric skills.

The Process of Developing an Assessment Checklist for Simulated Infant Respiratory Distress Using a Modified Delphi Method: A Mixed Methods Study.

Introduction Assessing clinical performance, such as managing respiratory distress, in clinical trainees is challenging yet important. Our objective was to describe and evaluate an integrative and iterative approach to developing a checklist measuring simulated clinical performance for infant respiratory distress. Methods We implemented a five-step modified Delphi process with an embedded qualitative component. An implementation period occurred followed by a second qualitative data collection. Validity evidence was collected throughout the process. Results A 19-item assessment checklist was developed for managing infant respiratory distress by medical student learners in a simulation-based setting. The iterative process provided content validity while the qualitative data provided response process validity. Cohen kappa was 0.82 indicating strong rater agreement. The assessment checklist was found to be easy to use and measure what was intended. Conclusion We developed an accurate and reliable assessment checklist for medical student learners in a simulation-based learning setting with high interrater reliability and validity evidence. Given its ease of use, we encourage medical educators and researchers to utilize this method to develop and implement assessment checklists for their interventions.