Citations

Purpose: The purpose of this study was to investigate the relationship between perceptual ratings of hypernasality made during connected speech and velopharyngeal (VP) gap size measured in millimeters in the sagittal plane during sustained vowel production using magnetic resonance imaging (MRI). Method: A retrospective cross-sectional analysis was completed. A subgroup of 110 participants from another study with an M age of 10.1 years presenting for management of VP insufficiency was included. Perceptual ratings of hypernasality during connected speech and measurement of gap size during sustained /i/ production on MRI were performed by raters blinded to the participants' medical and surgical history. Results: There was a moderate-to-strong, positive correlation ( r = .61; p < .001) between hypernasality ratings and VP gap size measured on MRI using sustained /i/. The odds of a higher hypernasality rating increased as the gap size increased (odds ratio = 1.34; 95% CI [1.20, 1.49]; p < .001). The predicted probability for hypernasality ratings of none/minimal/mild steadily decreased as the gap size increased indicating that lower ratings of hypernasality were associated with smaller gap sizes. For the rating of “moderate” hypernasality, the predicted probability of the rating steadily increased up to 8 mm and then decreased as the gap size continued to increase. The predicted probability for a hypernasality rating of “severe” consistently increased as the gap size increased. Conclusions: Hypernasality ratings made at the connected speech level were significantly associated with VP gap size as measured during sustained vowel production. These findings suggest sustained vowel production elicited on MRI may adequately characterize VP gap size in the evaluation of VP insufficiency.

Purpose The purpose of this study was to explore symptom management experiences among college students with type 1 diabetes mellitus (T1DM). Limited qualitative data using a theoretical framework exist that explore the self-care behavior processes for symptom management. Methods A qualitative approach was used for this study. The middle-range theory of self care of chronic illness served as a framework for data collection and analysis procedures. Data collection included distributing a survey to collect participants’ demographic and sociodemographic data and utilizing a semi-structured interview guide to conduct one-on-one interviews with 31 participants. Interviews occurred via Zoom (n = 28) and in person (n = 3). Interview transcripts were uploaded in NVivo for data management. The research team created a codebook using theoretical constructs to assist with thematic analysis. Data are representative of a sample whose characteristics include undergraduate students ages 18 to 23 living with T1DM for 2 years or more who attended large, public, 4-year universities located in the southeastern United States. Results Three main themes were created using theoretical constructs: symptom detection experiences, symptom interpretation experiences, and symptom response experiences. Two subthemes were identified for each theme. Participants engaged in symptom management for blood glucose regulation through detecting changes in their blood glucose physiologically and via technology. Additionally, symptom interpretation involved analyzing blood glucose trends and determining common causes of blood glucose changes. Symptom response included immediately addressing hypoglycemia but delayed responses addressing hyperglycemia. Conclusions Challenges were present responding to hypoglycemia; therefore, additional research is warranted to improve symptom response skills.

Abstract Objective To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise.

Abstract Gastric adenocarcinoma (GAC) is the fourth leading global cause of cancer mortality and leading infection-associated cancer. High-incidence regions of GAC include Latin America and Eastern Asia. Immigrants from high-incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, and its incidence rates are 2 to 10 times higher in non-White populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMC). Clinical trials of GPMC chemoprevention agents are lacking. We conducted a NCI Division of Cancer Prevention–funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis and intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva). The trial sites in Puerto Rico and rural Honduras had important characteristics: (i) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (ii) high prevalence of Helicobacter pylori infection and GPMCs; (iii) the absence of turmeric and curcuminoids in local diets; and (iv) proven bidirectional collaboration with U.S. academic institutions. H. pylori–negative patients with GPMCs were randomized to the study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included (i) an international regulatory environment; (ii) research infrastructure strengthening, particularly in Central America; (iii) participant recruitment in Honduras, wherein only 10% to 15% are H. pylori negative; (iv) the COVID-19 pandemic; and (v) natural disasters (three hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south–south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers, such as GAC.

Introduction The levator veli palatini (LVP) muscle has two segments with distinct roles in velopharyngeal function. Previous research suggests longer extravelar segments with shorter intravelar segments may lead to a more advantageous mechanism for velopharyngeal closure. The purpose of this study was to examine whether the distribution of the LVP intravelar and extravelar segments differs between children with cleft palate with and without VPI and controls. Methods The study included 97 children: 37 with cleft palate +/- lip with VPI, 37 controls, and 19 with cleft palate with normal resonance. Measures included mean LVP length, mean extravelar LVP length, and intravelar LVP length. Results Overall mean LVP length was similar ( P = .267) between controls and children with cleft palate (with and without VPI). However, there was a significant difference ( P < .001) between group for both intravelar and extravelar LVP lengths: the intravelar segment was significantly longer in those with VPI compared to controls and children with cleft palate and normal resonance; and the extravelar segment was significantly shorter in those with VPI compared to controls and children with cleft palate and normal resonance. Conclusions Results from this study demonstrate a significant difference between the distribution of the functional segments of the LVP among children with VPI, with a more disadvantageous distribution of the muscle segments among those with VPI.

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroids, and the rate of steroid-induced intraocular pressure (IOP) response. Materials and Methods: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race, and sex. All subjects had at least 3 eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspects were excluded. Results: Of the 10,073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mm Hg or more, significantly higher compared with 23% (5/22) of matched controls (P=0.031). Although more poor/intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups was similar (5.0±2.5 mm Hg in CYP3A4 poor/intermediate metabolizers compared with 4.1±2.1 mm Hg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0). Conclusion: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.

84 Background: Local therapies potentially offer a curative approach for patients with oligometastatic colorectal cancer (CRC). The effectiveness of systemic chemotherapy following definitive local treatment in this setting is not well-defined. Tumor-informed circulating tumor DNA (ctDNA) might guide management strategies after curative-intent local treatment. Methods: This is a single institution retrospective study of patients with CRC who underwent curative-intent local therapy to an isolated site of metastatic disease and had post-intervention tumor-informed ctDNA (Signatera) testing. The study was approved by the institutional review board. Clinical characteristics, including ctDNA results, were collected and evaluated. Kaplan-Meier method and log-rank test were used to calculate and compare disease-free survival (DFS). Factors associated with DFS were analyzed using multivariate Cox proportional hazards model. Results: 45 patients were included with median age of 59 years, 62% being male, 91% white, and 53% with stage IV disease at diagnosis. 37% of the patients had RAS mutations, no patient had BRAF mutation, and 2.2% patient had mismatch repair deficient disease. Isolated liver metastases were present in 80% of patients, lung metastases in 11% and other sites in 9%. 44 patients received chemotherapy prior to definitive treatment, with a median treatment duration of 16 weeks. ctDNA tests were done prior to local therapy in 23 patients, with 14 cases (61%) testing positive. Definitive treatment included resection (58%), ablation (13%), radiotherapy (4%), and multimodality (25%). Post-definitive treatment chemotherapy was administered to 24 (53%) patients. ctDNA positivity following definitive therapy was observed in 10 patients (22%), which was associated with a poorer prognosis, with a median DFS of 5.3 months compared to 21.3 months for the ctDNA-negative group (p<0.001). These findings were confirmed on multivariate analysis. In patients who had negative ctDNA after definitive local treatment, median DFS was 14.9 months for those who received post-intervention chemotherapy versus 21.3 months for those without post-intervention chemotherapy (p=0.835). Conclusions: Patients with negative ctDNA results following definitive local therapy for isolated metastatic CRC have better prognosis. Post-intervention chemotherapy in this group of patients was not associated with improved DFS. ctDNA guided omission of post-intervention chemotherapy following curative-intent local treatment of oligometastatic CRC warrants further study. [Table: see text]

Abstract Background: Circulating levels of THC and CBD may be altered when administered with medications that strongly or moderately inhibit or induce CYP450 enzymes responsible for metabolizing both substances. THC and CBD levels can also theoretically be altered in individuals who carry germline genetic variants or atypical phenotypes of CYP450 enzymes. In individuals where drug and gene interactions occur together, there could be a heightened impact on the circulating levels of THC and CBD. Materials and Methods: We conducted a retrospective chart review using a database of participants who previously completed pharmacogenomic testing and reported oral cannabis use in a medical encounter. Two pharmacogenomic-trained pharmacists reviewed medications and atypical variants in each participant to characterize the predicted effect of cannabis-drug, cannabis-gene, and cannabis-drug-gene interactions on circulating levels of THC and CBD. Results: Oral cannabis use was confirmed in 71 participants, with an average age of 68.5 years and primarily White women. Regarding THC metabolism, drug-only interactions were noted in 1 participant; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 38 participants; and 28 participants had no interactions. Concerning CBD metabolism, drug-only interactions were noted in 4 participants; both drug and gene interactions were noted in 4 participants; single- or combination-gene-only interactions were noted in 36 participants; and 27 participants had no interactions. Conclusion: This study is the first, to our knowledge, to conceptualize the potential impact of drugs and atypical phenotypes on altering circulating levels of THC and CBD in a clinical sample. The absence of published clinical outcomes in this field renders it challenging to estimate clinical significance of these findings. Until such data become available, leveraging the theoretical insights into drug interactions and atypical cannabis metabolism described in our study may serve as a tool to guide clinical care.

PURPOSE The enhanced, electronic health record (EHR)–facilitated cancer symptom control (E2C2) trial is a cohort cluster-randomized, stepped-wedge, hybrid type II trial that leverages EHR systems to facilitate a collaborative care model (CCM) approach with the goal of improving cancer symptom management. Understanding factors that influence care team adoption of EHR systems remains a critical understudied area of research. This study examines how oncology care teams' perceptions regarding the feasibility, acceptability, and appropriateness of E2C2 EHR systems preimplementation were associated with adoption 3 months after implementation and characterizes differences in adoption by individual- and system-level factors. METHODS Care team members completed an electronic survey before and 3 months after implementation of E2C2 for their respective sequence. Adoption was defined as frequency of use to statements aligned with care team–directed EHR systems designed to facilitate CCM approaches. Chi-square tests assessed differences in adoption while logistic regression models estimated associations between baseline mean scores of acceptability, feasibility, and appropriateness on care team adoption at 3 months. RESULTS Results from 94 care team members (37.2% oncologists, 72.6% female, 55.3% in their role for 6+ years) found that adoption rates ranged from 48.9% to 71.7%, with significant differences observed by location (community-based health care systems v tertiary medical center) and professional role. Adjusting for professional role, care team members reporting higher levels of perceived acceptability and appropriateness at baseline had greater odds of adopting EHR systems at 3 months. CONCLUSION EHR systems perceived as acceptable and appropriate are more likely to be adopted by oncology care teams in our sample. Future implementation efforts should consider tailored strategies to facilitate adoption of EHR systems designed to promote CCM-based approaches to improve cancer symptom management.