Exploring meningococcal serogroup B vaccination conversations under shared clinical decision-making in the US.

OBJECTIVE: In 2019, the United States Advisory Committee on Immunization Practices (ACIP) updated their meningococcal serogroup B (MenB) vaccination recommendation for 16-|23-year-olds from individual to shared clinical decision-making (SCDM). SCDM recommendations are individually based and informed by a decision process between patients and healthcare providers (HCPs). MenB vaccination among 16-23-year-olds remains low. We examined recorded conversations in which MenB vaccine-related discussions between HCPs and patients/caregivers took place, and how these interactions changed following the updated SCDM recommendation. METHODS: An analysis of recordings where MenB vaccination was discussed between HCPs and patients (16-|23 years old)/caregivers was conducted using retrospective anonymized dialogue data (January 2015-October 2022). Shared decision-making strength was measured using a modified OPTION5 framework. RESULTS: Of 97 included recorded conversations, the average duration was 11.3 min. Within these conversations, MenB disease was discussed for 0.25 min (38.9% of words in total vaccine-preventable diseases discussion) and MenB vaccination was discussed for 1.36 min (60.9% of words in total vaccine discussion), on average. HCPs spoke 78.8% of MenB vaccine-related words and most (99.0%) initiated the MenB vaccination discussion. In 40.2% of recordings, HCPs acknowledged the MenB vaccine without providing a clear recommendation. HCP recommendations often favored MenB vaccination (87.0%) and recommendations were 21.4% stronger post-recommendation change to SCDM. As measured by the modified OPTION5 framework, most recordings did not reflect a high degree of shared decision-making between HCPs and patients/caregivers. CONCLUSIONS: MenB vaccination discussions were brief, and the degree of shared decision-making was low. Targeted education of HCPs and patients/caregivers may improve MenB vaccination awareness, SCDM implementation, and vaccine uptake.

Meningitis is a serious and sometimes deadly disease. In the United States (US), the Centers for Disease Control and Prevention (CDC) recommends that 16­23-year-olds get vaccinated against meningococcal serogroup B (MenB), which causes a specific type of meningitis called invasive meningococcal disease. As of 2019, the CDC recommends that healthcare providers and patients or their caregivers have a shared decision-making discussion about deciding to get vaccinated against MenB. Despite these recommendations, vaccination against MenB among 16­23-year-olds is very low. Only about 3 in 10 17-year-olds had received the MenB vaccine in 2022. We studied conversations between healthcare providers and patients or their caregivers that included discussions of MenB vaccination. These discussions were largely brief and led by the healthcare providers. We found that healthcare providers most often made recommendations that were in favor of their patients getting vaccinated against MenB. However, we also found that healthcare providers missed many opportunities to have these shared decision-making discussions about MenB vaccination with patients or their caregivers. Providing education and resources for patients, caregivers, and healthcare providers focused on increasing awareness about MenB vaccination and the role they can play in having shared decision-making discussions may lead to more adolescents and young adults getting vaccinated against MenB. More research is needed to find out how we can improve MenB vaccination coverage in the US.

Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile.

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5-10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1 or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2 loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2 were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2-46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0-7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n = 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n = 530) and glioblastoma (n = 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n = 10), TSC cortical tubers (n = 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3; and TFs IRF6 and EOMES were all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2 loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1 or TSC2 and mTORC1 activation.