Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n = 53) or pencil beam scanning technique (PBS) (n = 74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n = 24) or two posterior oblique fields (n = 50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. RESULTS: Our cohort included 80 males and 47 females. The median age of patients was 10 years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n = 59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n = 16, 42%) than PS (n = 1, 4.7%) (p = .002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSION: Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

Development and evaluation of virtual simulation games to increase the confidence and self-efficacy of healthcare learners in vaccine communication, advocacy, and promotion.

BACKGROUND: Although healthcare providers (HCPs) are the most trusted source of vaccine information, there is a paucity of easily accessible, multidisciplinary educational tools on vaccine communication for them. Virtual simulation games (VSGs) are innovative yet accessible and effective tools in healthcare education. The objectives of our study were to develop VSGs to increase HCP confidence and self-efficacy in vaccine communication, advocacy, and promotion, and evaluate the VSGs' effectiveness using a pre-post self-assessment pilot study. METHODS: A multidisciplinary team of experts in medicine, nursing, pharmacy, and simulation development created three VSGs for HCP learners focused on addressing conversations with vaccine hesitant individuals. We evaluated the VSGs with 24 nursing students, 30 pharmacy students, and 18 medical residents who completed surveys and 6-point Likert scale pre-post self-assessments to measure changes in their confidence and self-efficacy. RESULTS: There were no significant differences in baseline confidence and self-efficacy across the three HCP disciplines, despite varied levels of education. Post-VSG confidence and self-efficacy (median: 5) were significantly higher than pre-VSG (median: 4-5) for all three HCP disciplines (P ≤ 0.0005), highlighting the effectiveness of the VSGs. Medical residents reported significantly lower post-VSG confidence and self-efficacy than nursing and pharmacy learners despite completing the most significant amount of education. CONCLUSIONS: Following the completion of the VSGs, learners in medicine, nursing, and pharmacy showed significant improvement in their self-assessed confidence and self-efficacy in holding vaccine conversations. The VSGs as an educational tool, in combination with existing clinical immunization training, can be used to increase HCP confidence and engagement in vaccine discussions with patients, which may ultimately lead to increased vaccine confidence among patients.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

BACKGROUND: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). METHODS AND MATERIALS: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. RESULTS: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. CONCLUSIONS: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. PLAIN LANGUAGE SUMMARY: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Prognostic Significance of Percentage and Size of Dedifferentiation in Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort's median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.

The NIH pediatric/young adult chordoma clinic and natural history study: Making advances in a very rare tumor.

BACKGROUND: Chordomas are rare tumors arising from the skull base and spine, with approximately 20 pediatric chordoma cases in the Unitedn States per year. The natural history and optimal treatment of pediatric chordomas, especially poorly differentiated and dedifferentiated subtypes, is incompletely understood. Herein, we present findings from our first National Cancer Institute (NCI) chordoma clinic and a retrospective analysis of published cases of pediatric poorly differentiated chordomas (PDC) and dedifferentiated chordomas (DC). METHODS: Patients less than 40 years old with chordoma were enrolled on the NCI Natural History and Biospecimens Acquisitions Study for Children and Adults with Rare Solid Tumors protocol (NCT03739827). Chordoma experts reviewed patient records, evaluated patients, and provided treatment recommendations. Patient-reported outcomes, biospecimens, and volumetric tumor analyses were collected. A literature review for pediatric PDC and DC was conducted. RESULTS: Twelve patients (median age: 14 years) attended the clinic, including four patients with active disease and three patients with PDC responsive to systemic therapy. Consensus treatment, management, and recommendations were provided to patients. Literature review returned 45 pediatric cases of PDC or DC with variable treatments and outcomes. CONCLUSIONS: A multidisciplinary expert clinic was feasible and successful in improving understanding of pediatric chordoma. While multimodal approaches have all been employed, treatment for PDC has been inconsistent and a recommended standardized treatment approach has not been defined. Centralized efforts, inclusive of specialized chordoma-focused clinics, natural history studies, and prospective analyses will help in the standardization of care for this challenging disease.

Characterizing the Pain Experience of Children With Acute Gastroenteritis Based on Identified Pathogens.

OBJECTIVES: Pain is common with acute gastroenteritis (AGE) yet little is known about the severity associated with specific enteropathogens. We sought to explore the correlation of pain severity with specific enteropathogens in children with AGE. METHODS: Participants were prospectively recruited by the Alberta Provincial Pediatric EnTeric Infection TEam at 2 pediatric emergency departments (EDs) (December 2014-August 2018). Pain was measured (by child and/or caregiver) using the 11-point Verbal Numerical Rating Scale. RESULTS: We recruited 2686 participants; 46.8% (n = 1256) females, with median age 20.1 months (interquartile range 10.3, 45.3). The mean highest pain scores were 5.5 [standard deviation (SD) 3.0] and 4.2 (SD 2.9) in the 24 hours preceding the ED visit, and in the ED, respectively. Prior to ED visit, the mean highest pain scores with bacterial detection were 6.6 (SD 2.5), compared to 5.5 (SD 2.9) for single virus and 5.5 (SD 3.1) for negative stool tests. In the ED, the mean highest pain scores with bacterial detection were 5.5 (SD 2.7), compared to 4.1 (SD 2.9) for single virus and 4.2 (SD 3.0) for negative stool tests. Using multivariable modeling, factors associated with greater pain severity prior to ED visit included older age, fever, illness duration, number of diarrheal or vomiting episodes in the preceding 24 hours, and respiratory symptoms, but not enteropathogen type. CONCLUSION: Children with AGE experience significant pain, particularly when the episode is associated with the presence of a bacterial enteric pathogen. However, older age and fever appear to influence children's pain experiences more than etiologic pathogens.

Sex differences and predictors of completion of a 6-month exercise-based cardiac rehabilitation program in 1,536 people following stroke.

OBJECTIVE: To retrospectively examine sex-differences and predictors of completion in consecutively-referred patients to a 6-month exercise-based cardiac rehabilitation program (CRP) from 2006 to 2017. MATERIALS/METHODS: People with hemiplegic gait participated in stroke-adapted-CRP; otherwise, traditional-CRP. Reasons for non-completion were ascertained by interview. Regression-analyses were conducted to determine non-completion in all patients and women and men separately. RESULTS: There were 1536 patients (30.3% women), mean age 64.5 ± 12.5 with 23% initiating the stroke-adapted-CRP. Overall, 75.1% completed the CRP (87.3% stroke-adapted-CRP vs 71.5% traditional-CRP; p < .001). There was no difference in completion between women and men (74.5% vs 75.4%; p=0.7), or in attendance to pre-scheduled sessions (p=0.6) or reasons for non-completion (p > .05, all). The only sex difference in completion by age (decade) occurred in those <41 years (59% women vs 85% men; p=.02). Baseline predictors of non-completion among all patients included not being enrolled in the stroke-adapted-CRP, lower V̇O2peak, smoking, diabetes (prescribed insulin) and depression but not sex (p=.5) or age (p=.15). Unique predictors in women vs men were younger age, lower V̇O2peak, smoking, diabetes (prescribed insulin), depression, and cancer diagnoses. Unique to men was having >1 stroke and diabetes (any anti-diabetes medication). The strongest predictor of non-completion among all models was not being enrolled in stroke-adapted-CRP. CONCLUSIONS: While there were no sex-differences in adherence to the CRP, women and men have mostly unique predictors of non-completion. Younger women are at greatest risk for non-completion. Practitioners should provide sex-specific, tailored strategies for enhancing completion with a focus on younger women and offering a stroke-adapted-CRP with close attention to those with diabetes.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

Parents' perceptions on COVID-19 vaccination as the new routine for their children ≤ 11 years old.

Canadian children 5-11 years old became eligible for COVID-19 vaccination on November 19, 2021, with eligibility for younger children expected later. We aimed to descriptively assess parents' COVID-19 vaccine intentions and acceptability of future doses, including co-administration and annual vaccination for their children. We conducted a cross-sectional Canadian online survey of parents from October 14-November 12, 2021, just prior to authorization of the pediatric formulation of the BNT162b2 COVID-19 vaccine for children aged 5-11 years. We assessed parents' intention to vaccinate their children aged 5-11 years, 2-4 years, and 6-23 months; reasons for their intention; and preferences for delivery and access to vaccines. Of 1129 parents, 56% intended to vaccinate their child aged 5-11 years against COVID-19; intentions were lower for children aged 6-23 months (41.9%) and 2-4 years (45.4%). Most parents who intended to vaccinate supported co-administration with routine (61.1%) or influenza (55.4%) vaccines, administration at school (63.6%), receipt of booster doses of COVID-19 vaccine (57.8%), and annual vaccination (56.4%) for their child. Despite parents' high COVID-19 vaccination uptake for themselves (88.8%), intentions for children aged 5-11 years was low. Currently, 56.9% of Canadian children aged 5-11 years have received one dose of a COVID-19 vaccine, and only 37.1% are fully vaccinated. Given that intentions for children <5 years was lower than those 5-11 years, we can also expect low uptake in this group. Parents' preferences regarding delivery and access to COVID-19 vaccination should be considered by public health officials when planning vaccination strategies for children.

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

PURPOSE: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. METHODS: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. RESULTS: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. CONCLUSION: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

Low-dose proton radiotherapy for pediatric choroidal hemangioma: A case series.

Management of pediatric choroidal hemangioma complicated by large exudative retinal detachment can be challenging, with few options available. Limited data have been published on outcomes following proton radiotherapy (PRT) for management of these patients. In this retrospective case series, nine patients were treated with a low-dose PRT regimen of 20 Gy(relative biological effectiveness [RBE]) in 10 fractions, and two were treated with 15 Gy(RBE) in four fractions. Visual acuity improved in seven patients (64%) and remained stable in the remaining four (36%). In patients with imaging follow-up (10 patients), subretinal fluid resolved in nine patients (90%) and tumor thickness decreased or remained stable in 10 (100%). Complications were observed in eight of 11 patients (73%). One patient developed grade 2 cataract; otherwise, no grade ≥2 complications were observed.

Measuring inequalities in COVID-19 vaccination uptake and intent: results from the Canadian Community Health Survey 2021.

BACKGROUND: By July 2021, Canada had received enough COVID-19 vaccines to fully vaccinate every eligible Canadian. However, despite the availability of vaccines, some eligible individuals remain unvaccinated. Differences in vaccination uptake can be driven by health inequalities which have been exacerbated and amplified by the pandemic. This study aims to assess inequalities in COVID-19 vaccination uptake and intent in adults 18 years or older across Canada by identifying sociodemographic factors associated with non-vaccination and low vaccination intent using data drawn from the June to August 2021 Canadian Community Health Survey (CCHS). METHODS: The CCHS is an annual cross-sectional and nationally representative survey conducted by Statistics Canada, which collects health-related information. Since September 2020, questions about the COVID-19 pandemic are asked. Adjusted logistic regression models were fitted to examine associations between vaccination uptake or intent and sociodemographic and health related variables. Region, age, gender, level of education, Indigenous status, visible minority status, perceived health status, and having a regular healthcare provider were considered as predictors, among other factors. RESULTS: The analysis included 9,509 respondents. The proportion of unvaccinated was 11%. Non-vaccination was associated with less than university education (aOR up to 3.5, 95% CI 2.1-6.1), living with children under 12 years old (aOR 1.6, 95% CI 1.1-2.4), not having a regular healthcare provider (aOR 1.6, 95% CI 1.1-2.2), and poor self-perceived health (aOR 1.8, 95% CI 1.3-2.4). Only 5% of the population had low intention to get vaccinated. Being unlikely to get vaccinated was associated with the Prairies region (aOR 2.2, 95% CI 1.2-4.1), younger age groups (aOR up to 4.0, 95% CI 1.3-12.3), less than university education (aOR up to 3.8, 95% CI 1.9-7.6), not being part of a visible minority group (aOR 3.0, 95% CI 1.4-6.4), living with children under 12 years old (aOR 1.8, 95% CI 1.1-2.9), unattached individuals (aOR 2.6, 95% CI 1.1-6.1), and poor self-perceived health (aOR 2.0, 95% CI 1.3-2.9). CONCLUSIONS: Disparities were observed in vaccination uptake and intent among various sociodemographic groups. Awareness of inequalities in COVID-19 vaccination uptake and intent is needed to determine the vaccination barriers to address in vaccination promotion strategies.

Transition to endemic: acceptance of additional COVID-19 vaccine doses among Canadian adults in a national cross-sectional survey.

BACKGROUND: Additional doses of COVID-19 vaccine have been proposed as solutions to waning immunity and decreased effectiveness of primary doses against infection with new SARS-CoV-2 variants. However, the effectiveness of additional vaccine doses relies on widespread population acceptance. We aimed to assess the acceptance of additional COVID-19 vaccine doses (third and annual doses) among Canadian adults and determine associated factors. METHODS: We conducted a national, cross-sectional online survey among Canadian adults from October 14 to November 12, 2021. Weighted multinomial logistic regression analyses were used to identify sociodemographic and health-related factors associated with third and annual dose acceptance and indecision, compared to refusal. We also assessed influences on vaccine decision-making, and preferences for future vaccine delivery. RESULTS: Of 6010 respondents, 70% reported they would accept a third dose, while 15.2% were undecided. For annual doses, 64% reported acceptance, while 17.5% were undecided. Factors associated with third dose acceptance and indecision were similar to those associated with annual dose acceptance and indecision. Previous COVID-19 vaccine receipt, no history of COVID-19 disease, intention to receive an influenza vaccine, and increasing age were strongly associated with both acceptance and indecision. Chronic illness was associated with higher odds of acceptance, while self-reported disability was associated with higher odds of being undecided. Higher education attainment and higher income were associated with higher odds of accepting additional doses. Minority first language was associated with being undecided about additional doses, while visible minority identity was associated with being undecided about a third dose and refusing an annual dose. All respondents reported government recommendations were an important influence on their decision-making and identified pharmacy-based delivery and drop-in appointments as desirable. Co-administration of COVID-19 and influenza vaccines was viewed positively by 75.5% of the dose 3 acceptance group, 12.3% of the undecided group, and 8.4% of the refusal group. CONCLUSIONS: To increase acceptance, targeted interventions among visible minority and minority language populations, and those with a disability, are required. Offering vaccination at pharmacies and through drop-in appointments are important to facilitate uptake, while offering COVID-19/influenza vaccine co-administration may have little benefit among those undecided about additional doses.

Sociodemographic Disparities in COVID-19 Vaccine Uptake and Vaccination Intent in Canada.

Introduction: This study's objective was to examine sociodemographic disparities in COVID-19 vaccine uptake and vaccination intent in the Canadian provinces by identifying factors associated with vaccine uptake in seniors prioritized for vaccination at the time of the survey and vaccination intent in all adults. Data and methods: A cross-sectional survey of Canadian adults was conducted in all provinces from mid-April to mid-May 2021. In addition to sociodemographic characteristics, respondents (n=10,678) provided information on their COVID-19 vaccination status or their intent to get vaccinated. Logistic regression models were fitted using sociodemographic factors as explanatory variables and vaccination status (unvaccinated vs at least one dose) or vaccination intent (unlikely versus likely or already vaccinated) as outcomes. To account for vaccine prioritization groups, multiple regression models were adjusted for province of residence, age, Indigenous identity and health care worker status. Results: Seniors with a lower household income (less than $60,000) and those living in smaller communities (fewer than 100,000 inhabitants) had higher odds of being unvaccinated. Among Canadian adults, the odds of being unlikely to get vaccinated were higher for males (adjusted odds ratio [AOR] 1.3), individuals younger than 60 (AOR between 3.3 and 5.1), non-health care workers (AOR 3.3), those with less than a high school education (AOR 3.4) or a household income of less than $30,000 (AOR 2.7) and individuals who do not identify as South Asian, Chinese, Black, Filipino, Arab, Latin American, Southeast Asian, West Asian, Korean or Japanese (AOR 1.7). Interpretation: COVID-19 vaccine uptake (80%) and vaccination intent (95%) were high among Canadians; however, relative disparities were observed among specific groups. Continued efforts targeted toward these groups are essential in reducing potential inequity in access or service provision.

Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality.

PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.

Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes.

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included. Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination. Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding. Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Attribution of Pediatric Acute Gastroenteritis Episodes and Emergency Department Visits to Norovirus Genogroups I and II.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis. With vaccines in development, population-based estimates of norovirus burden are needed to identify target populations, quantify potential benefits, and understand disease dynamics. METHODS: We estimated the attributable fraction (AF) for norovirus infections in children, defined as the proportion of children testing positive for norovirus whose gastroenteritis was attributable to norovirus. We calculated the standardized incidence and emergency department (ED) visit rates attributable to norovirus using provincial gastroenteritis visit administrative data. RESULTS: From 3731 gastroenteritis case patients and 2135 controls we determined that the AFs were 67.0% (95% confidence interval [CI], 31.5%-100%) and 91.6% (88.8%-94.4%) for norovirus genogroups I (GI) and II (GII), respectively. Norovirus GII AF varied by season but not age. We attributed 116 episodes (95% CI, 103-129) and 59 (51-67) ED visits per 10 000 child-years to norovirus GII across all ages, accounting for 20% and 18% of all medically attended gastroenteritis episodes and ED visits, respectively. CONCLUSIONS: In children, a large proportion of norovirus GII detections reflect causation, demonstrating significant potential for norovirus GII vaccines. Seasonal variation in the norovirus GII AF may have implications for understanding the role asymptomatic carriage plays in disease dynamics.

Intellectual functioning among case-matched cohorts of children treated with proton or photon radiation for standard-risk medulloblastoma.

BACKGROUND: Proton therapy may reduce cognitive deficits after radiotherapy among brain tumor survivors, although current data are limited to retrospective comparisons between historical cohorts. The authors compared intelligence quotient scores within a case-matched cohort of children with medulloblastoma treated with proton radiation (PRT) or photon radiation (XRT) over the same time period. METHODS: Among 88 consecutive patients with standard-risk medulloblastoma treated with PRT or XRT at 2 institutions from 2000 to 2009, 50 were matched 1:1 (25 with PRT and 25 with XRT) according to age, gender, date of diagnosis, histology, radiation boost, and craniospinal irradiation dose. One-way analyses of variance were performed to compare the Full-Scale Intelligence Quotient (FSIQ) and associated index scores between the 2 cohorts. RESULTS: Neurocognitive data were available for 37 survivors (17 with PRT and 20 with XRT) from the matched cohort. The mean age was 8.5 years (SD, 4.14 years). The median follow-up was 5.3 years (range, 1.0-11.4 years) and 4.6 years (range, 1.1-11.2 years) for the PRT and XRT cohorts, respectively (P = .193). Patients treated with PRT had significantly higher mean FSIQ (99.6 vs 86.2; P = .021), verbal (105.2 vs 88.6; P = .010), and nonverbal scores (103.1 vs 88.9; P = .011) than the XRT-treated cohort. Differences in processing speed (82.9 vs 77.2; P = .331) and working memory (97.0 vs 92.7; P = .388) were not statistically significant. CONCLUSIONS: Radiotherapy-associated cognitive effects appear to be more attenuated after proton therapy. Comprehensive prospective studies are needed to appropriately evaluate the neurocognitive advantages of proton therapy.