Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults.

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.

Challenges and Variations in Emergency Medicine Residency Training of Ultrasound-guided Regional Anesthesia Techniques.

BACKGROUND: Ultrasound guidance has become an integral component to procedural and diagnostic practice for the emergency physician. Whereas landmark-guided methods were used for peripheral nerve blocks in the past, the use of ultrasound has made regional anesthesia procedures faster, more successful, and feasible as a pain management modality in the emergency department. Not only the utilization, but also the teaching of ultrasound has become an essential aspect of emergency medicine residency training. Prior studies have found a substantial variation in practice and policies with regard to ultrasound-guided regional anesthesia (UGRA) and this translates to the education of both residents and fellows. OBJECTIVES: The objective was to describe the current state of UGRA education, trends, and barriers in emergency medicine residency and ultrasound fellowship programs in the United States. METHODS: A cross-sectional survey was conducted via the Internet utilizing the Qualtrics software platform. It was distributed to ultrasound directors and program directors of both Accreditation Council for Graduate Medical Education (ACGME) and American Osteopathic Association (AOA) accredited emergency medicine residency programs and ultrasound fellowships. Data analysis, cross-tabulation, and subgroup analysis were performed utilizing the software. RESULTS: We received a total of 138 responses (response rate of 66.3%). There was substantial variability with regard to implementing UGRA education. Additionally, there was a trend correlating a greater likelihood of UGRA education among programs with more than two ultrasound faculty members. Faculty training is considered to be the greatest barrier to teaching UGRA to residents and fellows. CONCLUSION: Resident and fellow education with regard to UGRA varies significantly among individual programs. Although there are currently no ACGME or AOA guidelines, nearly all residency programs believe that this is a skill that emergency physicians should learn. With the identification of key barriers and the need for an increased number of trained faculty, pain management utilizing UGRA may become an integral part to emergency medicine resident and fellow education.

New Ultrasound Technology Is a Useful Training Adjunct for Invasive Procedures.

BACKGROUND: The use of ultrasound for procedural guidance is an essential skill in emergency medicine (EM) and a required Accreditation Council for Graduate Medical Education (ACGME) competency for residents. Resident learners develop their skill set through hands-on training and may benefit from an intervention that encourages proper technique, bolsters confidence, and improves procedural success. Clear Guide ONE, a Food and Drug Administration-approved technology, overlays real-time virtual instrument navigation onto ultrasound displays to allow visualization of expected instrument trajectory prior to needle puncture, ensuring alignment with the target. OBJECTIVES: This study investigated computer-assisted instrument guidance as an educational tool for residents in a simulation environment. Primarily, the study evaluated residents' procedural speed and accuracy using ultrasound with and without the guidance device. METHODS: A total of 34 residents were observed performing ultrasound-guided needle placement in ballistic gel models with and without computer assistance in a simulation-based observational crossover study. Scan time before needle insertion, time to target, total procedure time, number of needle redirections, and procedural accuracy were measured. A total of 104 observations were recorded with 52 in each group. Paired-sample t-test analysis was used to compare group performance. Secondary outcomes were derived from survey data assessing resident opinions about the device. RESULTS: The computer-guidance group significantly outperformed the ultrasound-alone group in mean time to target, number of needle redirections, and procedural accuracy. There was no significant difference in mean scan time before needle insertion or total procedure time. Fifty percent of residents preferred the guidance system. Most residents (67%, n = 23) reported that the device increased confidence and the majority (94%, n = 32) reported perceived improvement in speed, accuracy, or both. CONCLUSIONS: Use of computer assistance technology for sonographic instrument guidance was successful in improving procedural accuracy, number of needle redirections, and time to target performance metrics and was well received by residents. This educational study suggests that this technology may emerge as a valuable tool in training EM residents to utilize ultrasound for procedures.

Emerging treatment options for myelofibrosis: focus on pacritinib.

Myelofibrosis (MF) is a myeloid malignancy associated with a heavy symptomatic burden that decreases quality of life and presents a risk for leukemic transformation. While there are limited curative treatments, the recent discovery of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway dysregulation has led to many clinical investigations for new treatment approaches. This review provides practical knowledge on the disease state, an overview of treatment options, and specifically focuses on the efficacy and safety of pacritinib in the management of MF. Pacritinib is a novel selective inhibitor of JAK2 and FMS-related tyrosine kinase 3 (FLT3) currently in Phase III trials for the treatment of MF. Thus far, studies have demonstrated clinical efficacy in reducing splenomegaly and constitutional symptoms. Common adverse events were gastrointestinal in nature, while hematologic toxicity was limited. However, it was announced that all ongoing clinical trials on pacritinib have been placed on hold by the US Food and Drug Administration in February 2016, due to concerns for increased intracranial hemorrhage and cardiac events. With comprehensive risk-benefit analysis of clinical trial data, the utility of pacritinib in the management of MF may be more clearly defined.

Clinical outcome indicators, disease prevalence and test request variability in primary care.

AIM: To describe differences in biochemistry test request rates (adjusted for practice size) between general practices and to investigate whether differences in HbA(1c) and thyroid function test request rates are related either to the practice prevalence of hypothyroidism and diabetes or to Quality and Outcome Framework (QOF) scores. METHODS: Information on test request rates, prevalence of diabetes and hypothyroidism, and QOF data over a one-year period were obtained from 58 practices covering a population of 284,609 patients. Spearman's rank correlation tests were used to investigate relationships between adjusted test request rates. RESULTS: There was wide variability in adjusted test request rates (lowest for HbA(1c) and highest for immunoglobulins). The ranking of practices for different tests was highly correlated. There was no relationship between adjusted test request rates for HbA(1c) and thyroid function and the reported prevalence of diabetes and hypothyroidism, respectively, nor was there any relationship with QOF scores in diabetes and hypothyroidism. CONCLUSIONS: There is wide variability in test request rates in general practice that do not appear to be related to disease prevalence or crude clinical outcome measures.