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If health providers are aware of their patients' literacy skills, they can more appropriately tailor their communication with patients. Few providers, however, assess patient's literacy skills for fear of offending patients, but no research has ever determined if patients object to such assessments. Our objectives were to determine the percentage of patients seen for routine health care that would agree to undergo literacy assessment and if satisfaction of patients differs in practices that perform literacy assessments versus practices that do not. We randomized 20 private and public medical practices to an intervention group that implemented literacy assessments with the Newest Vital Sign and a control group that did not. For intervention practices, we noted the percentage of patients agreeing to undergo the assessment. For both intervention and control practices, we assessed patient satisfaction. Of 289 patients asked to undergo literacy assessment in the intervention practices, 284 (98.3%) agreed to do so, including 125 (46.1%) with low or possibly low literacy skills. There was no difference in satisfaction between the intervention group and the control group. We conclude that patients are willing to undergo literacy assessments during routine office visits and performing such assessments does not decrease patient satisfaction. [ABSTRACT FROM AUTHOR]

In response to the growing population of older patients with incontinence, pharmaceutical companies are developing new drugs to treat the condition. Before prescribing medications for incontinence, however, physicians should determine the nature and cause of the patient's incontinence. The evaluation should rule out reversible conditions, conditions requiring special evaluation, and overflow bladder. The best treatment for urge incontinence is behavior therapy in the form of pelvic floor muscle exercises. Medications, used as an adjunct to behavior therapy, can provide additional benefit. Many therapies are available for patients with stress incontinence, including pelvic floor muscle exercise, surgery, intravaginal support devices, pessaries, peri-urethral injections, magnetic chairs, and intraurethral inserts. No medication has been approved for the treatment of stress incontinence, although medications are under development. [ABSTRACT FROM AUTHOR]

A large number of taxonomies are used to rate the quality of an individual study and the strength of a recommendation based on a body of evidence. We have developed a new grading scale that will be used by several family medicine and primary care journals (required or optional), with the goal of allowing readers to learn one taxonomy that will apply to many sources of evidence. Our scale is called the Strength of Recommendation Taxonomy. It addresses the quality, quantity, and consistency of evidence and allows authors to rate individual studies or bodies of evidence. The taxonomy is built around the information mastery framework, which emphasizes the use of patient-oriented outcomes that measure changes in morbidity or mortality. An A-level recommendation is based on consistent and good-quality patient-oriented evidence; a B-level recommendation is based on inconsistent or limited-quality patient-oriented evidence; and a C-level recommendation is based on consensus, usual practice, opinion, disease-oriented evidence, or case series for studies of diagnosis, treatment, prevention, or screening. Levels of evidence from 1 to 3 for individual studies also are defined. We hope that consistent use of this taxonomy will improve the ability of authors and readers to communicate about the translation of research into practice. [ABSTRACT FROM AUTHOR]

Gait disorders in the elderly are common and in most cases cannot be treated medically or surgically. Therefore, treatment often relies on ambulatory devices such as canes, crutches, and walkers. Before selecting a device, the patient should be evaluated to define whether one or both upper extremities are required to achieve balance or bear weight. Patients requiring only one upper extremity can use a cane, while patients requiring both upper extremities are best served by forearm crutches or walkers. The patient's need to bear weight through the device will help the physician choose a specific device. When measuring the device, anatomic landmarks and the angle of the elbow must be taken into consideration. Because time often is limited during a routine office visit, a physical therapist often can provide further training for patients learning to use such a device. [ABSTRACT FROM AUTHOR]

More than 90 million Americans have limited literacy skills, a burden that profoundly affects the quality of their health care. You can help by recognizing the problems, simplifying your written and oral communications, and verifying that patients have received and understood the message. [ABSTRACT FROM AUTHOR]

Low literacy is a pervasive and underrecognized problem in health care Approximately 21% of American adults are functionally illiterate, and another 27% have marginal literacy skills. Such patients may have difficulty reading and understanding discharge instructions, medication labels, patient education materials, consent forms, or health surveys. Properly assessing the literacy level of individual patients or groups may avoid problems in clinical care and research. This article reviews the use of literacy assessments, discusses their application in a variety of health care settings, and cites issues providers need to consider before testing. The authors describe informal and formal methods of screening for reading and comprehension in English and Spanish including the Rapid Estimate of Adult Literacy in Medicine, the Wide Range Achievement Test-3, the Cloze procedure, the Test of Functional Health Literacy in Adults, and others. Practical implications and recommendations for specific use are made. [ABSTRACT FROM AUTHOR]

In most cases, the evaluation of urinary incontinence requires only a history, a physical examination, urinalysis and measurement of postvoid residual urine volume. The initial purposes of the evaluation are to identify conditions requiring referral or specialized work-up and to detect and treat reversible causes that may be present. If the patient does not appear to require referral and a reversible cause is not identified, the next step is to categorize the patient's symptoms as typical of either urge or stress incontinence and treat the patient accordingly. If treatment fails or a presumptive diagnosis of urge or stress incontinence cannot be reached, the final step would be to perform more sophisticated tests or refer the patient for testing to define the cause and determine the best treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare performance of the newest vital sign (NVS) with existing literacy measures. Methods: We administered the NVS and REALM to 129 patients, and NVS and S-TOFHLA to 119 patients all in public clinics. Results: The NVS demonstrated high sensitivity for detecting limited literacy and moderate specificity (area under the receiver operating characteristic [AUROC] curve 0.71-0.73). The NVS was less effective than the S-TOFHLA for predicting health outcomes. Conclusion: The NVS is able to identify patients with limited literacy skills, but may misclassify those with ad- equate literacy according to the REALM and S-TOFHLA. NVS scores were not associated with health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To implement Ask-Me-3, a program that encourages patients to ask questions of physicians, in a low-income, predominantly Hispanic pediatric practice. Methods: We publicized Ask-Me-3 with posters/brochures in clinic. We interviewed parents before and 6 months after implementation to determine if they knew about and used the Ask-Me-3 questions. Results: No parents knew about Ask-Me-3 before implementation. Of 393 parents interviewed 6 months later, 42% knew about Ask-Me-3, and half of these used the questions. Conclusions: With a simple strategy for introducing Ask-Me-3, 20% of parents were using Ask-Me-3 six months later. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine readability and formatting characteristics of consumer medication information (CMI) accompanying prescription medication samples. METHODS: We collected the most commonly used prescription medication samples (n=100) from four out-patient clinics at a large teaching hospital in the Southeastern US. Seventeen percent of samples were not pills/tablets and of such diverse nature (e.g., injections, drops, and creams) that there were not enough in any category to draw conclusions. Therefore, our analyses were limited to 83pill/tablet samples, belonging to 11 drug classes (e.g., cardiovascular, and psychiatric). We noted if CMI was present, and if so we assessed it for how instructions were presented, reading level, text size, format/layout, and comprehensibility. RESULTS: No CMI was present in 39 (46.9%) samples. In 19 (22.9%), CMI was contained in a package insert and in 25 (30.2%) it was printed on the medication package. Average reading difficulty of CMI was at the 10th grade level (range=6-15) using the Fry formula, and text point size was small (mean 9.9+/-2.2 on package inserts and 9.4+/-2.6 when printed on packages). CONCLUSIONS: Almost half of samples did not include any type of CMI. For those that had CMI, it was often written at a reading difficulty level higher than the average reading skills of American adults, and the format of most CMI was not optimal for comprehensibility. It is likely that many patients do not understand the instructions accompanying medication samples they receive from clinicians. PRACTICE IMPLICATIONS: Clinicians should be cognizant of the shortcomings of CMI accompanying medication samples and thereby, distribute them to patients with caution. Manufacturers too should consider revising CMI to comply with low-literacy guidelines. [ABSTRACT FROM AUTHOR]

Competing Interests: This publication was supported by an institutional Clinical and Translational Science Award, National Institutes of Health/National Center for Advancing Translational Sciences (grant 1UL1TR001425) through the University of Cincinnati. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. This work was additionally supported by divisional funding from the Heart Institute, Cincinnati Children’s Hospital Medical Center. This work was completed in partial fulfillment of the Master of Science degree in Clinical and Translational Research in the Division of Epidemiology, University of Cincinnati College of Medicine. Dr Hill serves as a consultant for Ultragenyx. Dr De Blank has served as an Advisory Board member for Alexion Pharmaceuticals for selumetinib. Dr Kumar serves as a consultant for Sobi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background/aims: We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement and evaluated its feasibility, reliability, and validity., Methods: Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children in a clinical trial (NCT01362803) at baseline and 1 year on selumetinib treatment for plexiform neurofibromas ( n  = 20) and of untreated participants with plexiform neurofibromas ( n  = 4). Raters, blinded to treatment and timepoint, completed the 0-10 disfigurement severity score for plexiform neurofibroma on each image (0 = not at all disfigured, 10 = very disfigured). Raters evaluated the ease of completing the scale, and a subset repeated the procedure to assess intra-rater reliability., Results: Mean baseline disfigurement severity score for plexiform neurofibroma ratings were similar for the selumetinib group (6.23) and controls (6.38). Mean paired differences between pre- and on-treatment ratings was -1.01 (less disfigurement) in the selumetinib group and 0.09 in the control ( p  = 0.005). For the disfigurement severity score for plexiform neurofibroma ratings, there was moderate-to-substantial agreement within rater cohorts (weighted kappa range = 0.46-0.66) and agreement between scores of the same raters at repeat sessions ( p  > 0.05). In the selumetinib group, change in disfigurement severity score for plexiform neurofibroma ratings was moderately correlated with change in plexiform neurofibroma volume with treatment ( r  = 0.60)., Conclusion: This study demonstrates that our observer-rated disfigurement severity score for plexiform neurofibroma was feasible, reliable, and documented improvement in disfigurement in participants with plexiform neurofibroma shrinkage. Prospective studies in larger samples are needed to validate this scale further., Competing Interests: Declaration of conflicting interestsDr B.C.W. and Dr A.M.G. have unpaid advisory roles for AstraZeneca and SpringWorks. Dr M.J.F. has paid advisory roles for AstraZeneca and SpringWorks and research support from AstraZeneca, Array BioPharma, and Exelixis for plexiform neurofibroma clinical trials. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Dr M. B. has a paid advisory role on the external advisory board for the Koselugo Registry through Alexion.

Background: Neuroblastoma risk stratification relies on prognostic risk factors and image-defined risk factors (IDRFs). Evaluating neuroblastoma typically involves magnetic resonance imaging (MRI) with gadolinium-based contrast media (GBCM, "contrast"). However, there are concerns regarding adverse effects and cost of GBCM. We aimed to assess the impact of intravenous GBCM on interobserver agreement for neuroblastoma staging on baseline MRI., Procedure: We reviewed baseline MRI scans of 50 children with abdominopelvic neuroblastomas confirmed by histopathology. Duplicate sets of images were created, with post-contrast T1-weighted sequences removed from one set. Four pediatric radiologists independently analyzed the scans in a randomized manner. They recorded primary tumor size, presence of IDRFs, and metastatic lesions. Agreement among the reviewers was measured using kappa and Fleiss kappa statistics., Results: Mean age of included children was 3.3 years (range: 0.01-14.9 years), and 20 [40%] were females. Mean tumor size was 5.7 cm in greatest axial diameter. Pre-contrast versus post-contrast MRI showed excellent agreement for tumor measurement. Overlapping confidence intervals (CIs) were seen in nearly all categories of interobserver agreement on the presence or absence of individual IDRFs, with agreement ranging from poor to substantial, regardless of the presence of contrast. The overall interobserver agreement on the presence of at least one IDRF was substantial with contrast (kappa = .63; 95% CI: .52-.75) and moderate without contrast (kappa = .5; 95% CI: .39-.61); although the overlapping CIs suggest a lack of meaningful difference. Similarly, interobserver agreement on the presence or absence of individual sites of metastatic disease ranged from poor to substantial. The interobserver agreement on the overall determination of presence of metastatic disease was fair with contrast (kappa = .49; 95% CI: .38-.61) and moderate without contrast (kappa = .71; 95% CI: .59-.826)., Conclusions: Contrast does not improve tumor size measurement or radiologist agreement on the presence or absence of IDRFs or metastatic disease in children with newly diagnosed neuroblastoma., (© 2023 Wiley Periodicals LLC.)

Introduction: Nationally, suicide ideation prevalence is comparable among White, American Indian/Alaska Native, Black, and Hispanic adults experiencing alcohol use disorder. This study examines whether such comparability extends to the probability of receiving a suicide ideation diagnosis when presenting with alcohol use disorder at emergency departments. The probability of hospitalization following such diagnosis is examined as well., Methods: National Emergency Department Sample (2019) data were used. Logistic and multilevel logistic regression analyses were performed in 2022-2023 with suicide ideation diagnosis and subsequent hospitalization as the outcome variables. Control variables included demographics, payor, alcohol use disorder level, comorbidities, and emergency department facility. Adjusted probabilities were computed., Results: Age-adjusted probabilities of suicide ideation diagnoses for American Indian/Alaska Native, Black, and Hispanic patients with alcohol use disorder were 5.4%, 6.7%, and 4.9% (95% CIs=3.7, 7.1; 6.0, 7.4; 4.4, 5.4), respectively; all less than that for White counterparts (8.7%; 95% CI=8.2, 9.2). Among patients with alcohol use disorder plus suicide ideation diagnoses, the age-adjusted probability of hospitalization for American Indians/Alaska Natives (32.4%; 95% CI=20.9, 44.0) was less than that for Whites, Blacks, and Hispanics (49.8%, 52.3%, and 49.9%; 95% CIs=46.7, 52.8; 47.1, 57.5; and 43.9, 55.8, respectively). In regressions with multiple control variables, the racial/ethnic differences remained statistically significant (p<0.05)., Conclusions: Diagnosis of suicide ideation, a key step in emergency department suicide prevention care, occurred significantly less often for patients of color with alcohol use disorder than for White counterparts. American Indians/Alaska Natives, the racial/ethnic group known to have the nation's highest suicide rate, had the lowest probability of being hospitalized after a diagnosis of alcohol use disorder plus suicide ideation., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies., Methods: This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index)., Results: For the 74 children (median age 10.3 years; range 3-18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment., Conclusions: With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2023.)

Problem : Writing for publication is a core activity for many medical school faculty, but faculty report numerous challenges to publication. To help address these challenges, some medical schools establish writing support programs, but those programs are often resource-intensive, involving didactic courses, accountability groups, formal mentorships, and even assistance from professional writers. Not all medical schools, however, provide resources for such programs, and many faculty members, especially clinicians, lack time needed to participate. Furthermore, success of these programs is typically judged by the total number of papers published. However, many clinicians would judge success as publication of the occasional papers they decide to write, not the total number of papers they or the group publish. With these issues in mind, we established a low-resource writing program focused on individual acceptance rates rather than total publications. Intervention : Our writing program is an informal group that meets monthly. Members bring their ideas for papers and drafts of papers, and other members provide critique and suggestions for improvement. Members then revise their papers to address that critique prior to journal submission. There are no formal or assigned mentors, courses, lectures, or writing assistants. Context : The program takes place in our family medicine department, in which faculty have various roles. Some group members are clinician-educators seeking to publish occasional clinical reviews or research articles; others are PhDs seeking to publish on aspects of their work. Impact : During the six years of the program, 86% of papers reviewed by the group were accepted for publication and 94% of those were accepted by the journal to which they were first submitted. Publication success rate of individual members averaged 79%. This exceeds the 30-40% acceptance rate for scholarly journals worldwide. Group members published an average of 5.2 papers per member, with some publishing as few as 2-3 papers and others as many as 10-11. Lessons Learned : An informal, low-resource writing program in medical school departments can help faculty reach their publication goals. We found that members were satisfied by having the group help them publish whatever number of papers they decided to write. The program's simple, informal approach fostered a culture of respectful and collegial interactions, in which members learned to depend on and accept critiques from colleagues. Finally, an unexpected benefit of our program resulted from membership of both clinicians and non-clinicians. This provided feedback from individuals with different perspectives, which enhanced development of manuscripts.

Vα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB). The primary objectives were safety and determination of maximum tolerated dose (MTD). The anti-tumor activity of GD2-CAR.15 NKTs was assessed as a secondary objective. Immune response evaluation was an additional objective. No dose-limiting toxicities occurred; one patient experienced grade 2 cytokine release syndrome that was resolved by tocilizumab. The MTD was not reached. The objective response rate was 25% (3/12), including two partial responses and one complete response. The frequency of CD62L + NKTs in products correlated with CAR-NKT expansion in patients and was higher in responders (n = 5; objective response or stable disease with reduction in tumor burden) than non-responders (n = 7). BTG1 (BTG anti-proliferation factor 1) expression was upregulated in peripheral GD2-CAR.15 NKTs and is a key driver of hyporesponsiveness in exhausted NKT and T cells. GD2-CAR.15 NKTs with BTG1 knockdown eliminated metastatic NB in a mouse model. We conclude that GD2-CAR.15 NKTs are safe and can mediate objective responses in patients with NB. Additionally, their anti-tumor activity may be enhanced by targeting BTG1. ClinicalTrials.gov registration: NCT03294954 ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy., Patients and Methods: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria., Results: One hundred forty-six patients were included. Tumors were MYCN -amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF., Conclusion: Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefits for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low-grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

Background: Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity., Methods: Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures were performed every 4 cycles for 2 years, with changes assessed over time. A confirmed partial response (cPR) was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart., Results: 72% of subjects experienced a cPR on selumetinib. Participants received selumetinib for a median of 41 cycles (min 2, max 67) at data cutoff. Approximately half of the children rated having some target tumor pain at baseline, which significantly decreased by pre-cycle 13. Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment., Conclusions: Selumetinib resulted in PN shrinkage in most subjects with NF1 PN without clinically significant morbidity. No new PN-related symptoms developed while on selumetinib, and PRO measures indicated declines in tumor-related pain intensity. This supports that selumetinib treatment may prevent the development of PN-related morbidities, though future prospective studies are needed to confirm these results., Clinical Trial Registration: ClinicalTrials.gov NCT01362803., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

Background: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors., Methods: STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D., Results: At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4)., Conclusions: Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Introduction: There is a growing concern that certain public health restrictions imposed to prevent the spread of coronavirus disease 2019 (COVID-19) could result in more violence against women (VAW). We sought to determine if the rates and types of VAW changed during the COVID-19 pandemic at our level 1 trauma center (L1TC)., Methods: We performed a retrospective review of female patients who presented to our L1TC because of violence from 2019 through 2020. Patients were grouped into a pre-COVID or COVID period. The primary aim of this study was to compare rates of VAW between groups. Secondary aims sought to evaluate for any difference in traumatic mechanism between periods and to determine if a temporal relationship existed between COVID-19 and VAW rates., Results: There was no difference in rates of VAW between the pre-COVID and COVID period (3.1% vs 3.6%, P = .6); however, rates of penetrating trauma were greater during the COVID period (38.2% vs 10.3%, P = .01). After controlling for patient age and race, the odds of penetrating trauma increased during the pandemic (OR 5.8, 95% CI 1.6-28.5, P < .01). From February 2020 through October 2020, there was a direct relationship between rates of COVID-19 and VAW ( r 2 .78, P < .01)., Conclusion: Rates of VAW were unchanged between the pre-COVID and COVID periods, yet the odds of penetrating VAW were 5 times greater during the pandemic. Moving forward, trauma surgeons must remain vigilant for signs of violence and ensure that support services are available during future crises.

Introduction: 131 I-meta-iodobenzylguanidine ( 131 I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131 I - MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma., Methods: Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an 131 I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131 I-MIBG feasibility; those who completed 131 I-MIBG therapy were evaluable for assessment of 131 I-MIBG + Bu/Mel feasibility., Results: Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received 131 I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for 131 I-MIBG + Bu/Mel received this combination. Among those who received 131 I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131 I-MIBG and 131 I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%)., Conclusion: This pilot trial demonstrated feasibility and tolerability of administering 131 I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131 I-MIBG during induction therapy., (© 2021 Wiley Periodicals LLC.)

Background: 18 F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) shows tumor activity in most neuroblastomas, but the role of 18 F-FDG PET/CT in neuroblastoma remains to be defined., Objective: This study explored the prognostic significance of 18 F-FDG PET in newly diagnosed neuroblastic tumors., Materials and Methods: This retrospective study reviewed all 18 F-FDG PET/CT examinations performed for a new diagnosis of suspected neuroblastoma. MYCN amplification status, tumor recurrence and survival were abstracted from the medical record. Primary tumors were manually segmented to measure maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), tumor volume and total lesion glycolysis. Univariate and multivariable analyses using Cox proportional hazards regression testing assessed the predictive performance of PET indices for event-free survival and overall survival with thresholds determined using receiver operating characteristic curve analysis., Results: Fifty-five children were included, with a median age of 2.9 years (interquartile range [IQR] 1.8-3.0 years). SUV max , tumor volume and total lesion glycolysis were higher in MYCN-amplified tumors (P=0.012, P<0.0001, P<0.0001, respectively) and in higher International Neuroblastoma Risk Group (INRG) stages (P=0.0008, P=0.0017, P=0.0017, respectively). After adjusting for age, tumor SUV max (P=0.028) and SUV mean (P=0.045) were associated with overall survival. An SUV max threshold of 4.77 (P=0.028) best predicted overall survival, with median overall survival of 2,604 days (SUV max >4.77) vs. >2,957 days (SUV max ≤4.77). No PET parameters were independently significantly associated with overall survival or event-free survival after controlling for MYCN status, stage or treatment risk stratification., Conclusion: Tumor metabolic activity is higher in higher-stage MYCN-amplified neuroblastic tumors. Higher SUV max and SUV mean were associated with worse overall survival but were not independent of other prognostic markers.

Consolidation using high-dose chemotherapy with autologous stem cell transplantation (ASCT) is an important component of frontline therapy for children with high-risk neuroblastoma. The optimal preparative regimen is uncertain, although recent data support a role for busulfan/melphalan (BuMel). The Children's Oncology Group (COG) conducted a trial (ANBL12P1) to assess the tolerability and feasibility of BuMel ASCT following a COG induction. Patients with newly diagnosed high-risk neuroblastoma who did not progress during induction therapy and met organ function requirements received i.v. busulfan (every 24 hours for 4 doses based on age and weight) and melphalan (140 mg/m 2 for 1 dose), followed by ASCT. Busulfan doses were adjusted to achieve to an average daily area under the curve (AUC) <5500 µM × minute. The primary endpoint was the occurrence of severe sinusoidal obstruction syndrome (SOS) or grade ≥4 pulmonary complications within the first 28 days after completion of consolidation therapy. A total of 146 eligible patients were enrolled, of whom 101 underwent BuMel ASCT. The overall incidence of protocol-defined unacceptable toxicity during consolidation was 6.9% (7 of 101). Six patients (5.9%) developed SOS, with 4 (4%) meeting the criteria for severe SOS. An additional 3 patients (3%) experienced grade ≥4 pulmonary complications during consolidation. The median busulfan AUC was 4558 µM × min (range, 3462 to 5189 µM × minute) for patients with SOS and 3512 µM × min (2360 to 5455 µM × minute) (P = .0142). No patients died during consolidation. From the time of study enrollment, the mean 3-year event-free survival for all 146 eligible patients was 55.6 ± 4.2%, and the mean 3-year overall survival was 74.5 ± 3.7%. The BuMel myeloablative regimen following COG induction was well tolerated, with acceptable pulmonary and hepatic toxicity., (Copyright © 2021. Published by Elsevier Inc.)

Autologous hematopoietic cell transplant (aHCT) has a significant survival advantage in patients with high-risk (HR) neuroblastoma. Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication and may result in chronic renal disease leading to delay in subsequent posttransplant therapy and limitations of treatment options. Dinutuximab represents an important therapeutic advance in the treatment of pediatric HR neuroblastoma, but historically has not been administered in patients with GFR < 60 mL/m 2 /min. Here, we present the safe outcome of dinutuximab administration while on renal replacement therapy in two cases of HR neuroblastoma with end-stage renal disease secondary to TA-TMA., (© 2020 Wiley Periodicals LLC.)

Introduction: The prevalence of kidney stones is rising and there is an increasing demand for reliable, easy to understand information for patients. To evaluate the readability of common Internet-based resources for kidney stones, we examined whether the most popular online educational materials may be contributing to decreased health literacy for this chronic condition., Methods: Websites for readability analysis were chosen based on a Google.com search using the search term "kidney stones." The top 10 websites were chosen for analysis and their quality was assessed by the presence or absence of a HONcode certificate. Readability was determined using 6 readability assessment tools: Flesch Reading Ease, FORCAST, Fry, Gunning Fog, Raygor Estimate and Simple Measure of Gobbledygook. Each website was then analyzed by subsections, with emphasis on the treatment and prevention of kidney stones., Results: Of the 10 websites analyzed 8 had HONcode certification. Grade level calculations ranged from 7-13.9. All 10 websites were found to have readability levels above the recommended sixth-grade reading level. Mean Flesch Reading Ease score was 59 (range 47-73). With respect to treatment and prevention sections, 6/10 and 5/10 websites had readability levels above a tenth-grade level, respectively., Conclusions: The most commonly accessed websites regarding kidney stones have readability scores above what is comprehensible to the general public, with most exceeding grade level recommendations from the American Medical Association. Websites pertaining to kidney stones need to be simplified to facilitate patient understanding, especially with respect to the treatment and prevention of kidney stones.

Purpose: Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients with NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis., Methods: Inclusion criteria included age ≥ 16 years and a PN that was either progressive or causing significant morbidity. First-dose pharmacokinetics were performed. Patients completed patient-reported outcome measures. Patients received mirdametinib by mouth twice a day at 2 mg/m 2 /dose (maximum dose = 4 mg twice a day) in a 3-week on/1-week off sequence. Each course was 4 weeks in duration. Evaluations were performed after four courses for the first year and then after every six courses. Patients could receive a maximum of 24 total courses., Results: Nineteen patients were enrolled, and all 19 received mirdametinib. The median age was 24 years (range, 16-39 years); the median baseline tumor volume was 363.8 mL (range, 3.9-5,161 mL). Eight of the 19 patients (42%) achieved a partial response of the target PN by course 12, and 10 (53%) had stable disease. One patient (5%) developed progressive disease at course 8. Significant and durable decreases were observed in pain ratings., Conclusion: To our knowledge, this analysis represents the first characterization of the activity and pharmacokinetics of mirdametinib in patients with NF1 and PNs and is the first published response study for MAPK/ERK kinase inhibitors in adults with NF1 and PNs. Mirdametinib given at 2 mg/m 2 /dose (maximum dose, 4 mg) twice daily in a 3-week on/1-week off sequence resulted in a 42% partial response rate with preliminary evidence of reduction in pain.