Examining the Critical Need for Tailored Adolescent Opioid Education: A National Study.

OBJECTIVE: Prescription opioid education can be a preventative measure for opioid misuse. However, most research focuses on adult perspectives rather than adolescents. This study aimed to understand adolescents' attitudes, perceptions, knowledge about prescription opioids, and preferences and prior educational exposure to opioid safety. METHODS: Data were collected from November to December 2020. Quota sampling through Qualtrics was used to recruit a national sample of 13- to 18-year-old adolescents who lived in the United States and could understand English. RESULTS: A total of 774 responses were analyzed. The most frequently reported source of opioid information was speaking with parents (72%). More than half (54.7%) of participants preferred technology-based education. Participants with a personal history of opioid prescription scored no differently on safe handling and storage of opioids. There was a strong relationship between participants who reported prior knowledge of what opioids are and stopping their friend from using an opioid medication for non-medical purposes (χ2 (1, N = 684) = 3.5; p = 0.042). Participants with prior education on opioid disposal did not know that -returning opioids to the pharmacy was correct (χ2 (1, N = 425) = 3.8; p = 0.254). CONCLUSIONS: Participants were less knowledgeable about safe storage and disposal of opioids, preferred technology-based education, and were extremely likely to talk to their parents about opioid information. Findings reaffirm the significance of opioid safety education and communication between adolescents and parents. Adolescent demographic characteristics, preferences, and prior knowledge should be considered when providing opioid safety education.

Inpatient Pediatric Care and Clinician Workforce in Wisconsin: The State of the State.

INTRODUCTION: Availability of inpatient pediatric services declined across the United States from 2008 through 2018, with rural areas experiencing steepest declines. Despite the movement of pediatric care to children's centers, most children are still cared for in community hospitals nationally. Assessing the availability and providers of inpatient pediatric care in Wisconsin is an important step in ensuring the health care needs of children in the state continue to be met. METHODS: A cross-sectional survey was distributed to Wisconsin hospitals to determine pediatric services and physician workforce. The response rate was 130/138 (94%), including 56/58 (97%) critical access hospitals. Results of specific inpatient pediatric subdivisions were analyzed by descriptive statistics. RESULTS: Hospitals that provide inpatient newborn care are mostly staffed by pediatricians and family physicians, while critical access hospitals are staffed by family physicians. Hospitals with neonatal intensive care units are staffed by neonatologists, with telemedicine utilized in critical access hospitals. Hospitals with general pediatric admissions are staffed by pediatricians or family physicians, while critical access hospitals are staffed by family physicians. Hospitals with pediatric intensive care units are staffed by pediatric intensivists. CONCLUSIONS: Despite workforce disparities and shortages, hospitals across Wisconsin, including many critical access hospitals, continue to provide inpatient pediatric services. Family physicians play a major role in the pediatric health care delivery in Wisconsin hospitals. Robust inpatient pediatric training of family physicians may enable rural health authorities to continue addressing the gaps that persist in inpatient pediatric care accessibility.

Identifying Young Adults at High Risk for Weight Gain Using Machine Learning.

INTRODUCTION: Weight gain among young adults continues to increase. Identifying adults at high risk for weight gain and intervening before they gain weight could have a major public health impact. Our objective was to develop and test electronic health record-based machine learning models to predict weight gain in young adults with overweight/class 1 obesity. METHODS: Seven machine learning models were assessed, including three regression models, random forest, single-layer neural network, gradient-boosted decision trees, and support vector machine (SVM) models. Four categories of predictors were included: 1) demographics; 2) obesity-related health conditions; 3) laboratory data and vital signs; and 4) neighborhood-level variables. The cohort was split 60:40 for model training and validation. Area under the receiver operating characteristic curves (AUC) were calculated to determine model accuracy at predicting high-risk individuals, defined by ≥ 10% total body weight gain within 2 y. Variable importance was measured via generalized analysis of variance procedures. RESULTS: Of the 24,183 patients (mean [SD] age, 32.0 [6.3] y; 55.1% females) in the study, 14.2% gained ≥10% total body weight. Area under the receiver operating characteristic curves varied from 0.557 (SVM) to 0.675 (gradient-boosted decision trees). Age, sex, and baseline body mass index were the most important predictors among the models except SVM and neural network. CONCLUSIONS: Our machine learning models performed similarly and had modest accuracy for identifying young adults at risk of weight gain. Future models may need to incorporate behavioral and/or genetic information to enhance model accuracy.

Evaluation of an implementation package to deliver the COPD CARE service.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and is estimated to be the leading cause of death in the next 15 years. Patients with COPD suffer from persistent chronic cough, sputum production and exacerbations leading to deteriorating lung function, worsening quality of life and loss of independence. While evidence-based interventions exist to improve the well-being of patients with COPD, incorporation of these interventions into routine clinical care is challenging. Chronic Obstructive Pulmonary Disease Coordinated Access to Reduce Exacerbations (COPD CARE) is a team-based, coordinated care transitions service integrating evidence-based interventions for COPD management within the patient care delivery model to reduce readmissions. This evaluation considers the process of scaling the COPD CARE service across medical facilities using an implementation package designed for service expansion. The implementation package was developed at the United States Veterans Health Administration and implemented at two medical centres. Core dissemination and implementation science methods were applied to guide design and delivery of the implementation package.The aims of this evaluation were to (1) evaluate the impact of the implementation package on use of evidence-based interventions for COPD management and (2) explore clinician perceptions of the implementation package. This prospective mixed-methods quality improvement project included two Plan Do Check Act (PDCA) cycles conducted over a 24-month period. Electronic health record data demonstrated significant improvements in the count of evidence-based interventions incorporated into routine clinical care after training completion (p<0.001), offering preliminary effectiveness of the package to improve uptake of best practices for COPD management. Clinician perceptions of the implementation package, measured by questionnaire at multiple time points, demonstrated significant improvements for all scales at the end of the final PDCA cycle. Clinicians described the implementation package as positively impacting clinician confidence, interprofessional collaboration and patient care delivery.

KIR/KIR-ligand genotypes and clinical outcomes following chemoimmunotherapy in patients with relapsed or refractory neuroblastoma: a report from the Children's Oncology Group.

BACKGROUND: In the Children's Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined with either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) and granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among patients treated with I/T/DIN/GM-CSF in the initial cohort (n=17) was 53%; additional patients were enrolled to permit further evaluation of this chemoimmunotherapy regimen. Potential associations between immune-related biomarkers and clinical outcomes including response and survival were evaluated. METHODS: Patients were evaluated for specific immunogenotypes that influence natural killer (NK) cell activity, including killer immunoglobulin-like receptors (KIRs) and their ligands, Fc gamma receptors, and NCR3. Total white cells and leucocyte subsets were assessed via complete blood counts, and flow cytometry of peripheral blood mononuclear cells was performed to assess the potential association between immune cell subpopulations and surface marker expression and clinical outcomes. Appropriate statistical tests of association were performed. The Bonferroni correction for multiple comparisons was performed where indicated. RESULTS: Of the immunogenotypes assessed, the presence or absence of certain KIR and their ligands was associated with clinical outcomes in patients treated with chemoimmunotherapy rather than I/T/TEMS. While median values of CD161, CD56, and KIR differed in responders and non-responders, statistical significance was not maintained in logistic regression models. White cell and neutrophil counts were associated with differences in survival outcomes, however, increases in risk of event in patients assigned to chemoimmunotherapy were not clinically significant. CONCLUSIONS: These findings are consistent with those of prior studies showing that KIR/KIR-ligand genotypes are associated with clinical outcomes following anti-GD2 immunotherapy in children with neuroblastoma. The current study confirms the importance of KIR/KIR-ligand genotype in the context of I/T/DIN/GM-CSF chemoimmunotherapy administered to patients with relapsed or refractory disease in a clinical trial. These results are important because this regimen is now widely used for treatment of patients at time of first relapse/first declaration of refractory disease. Efforts to assess the role of NK cells and genes that influence their function in response to immunotherapy are ongoing. TRIAL REGISTRATION NUMBER: NCT01767194.

Radiation to all macroscopic sites of tumor permits greater systemic antitumor response to in situ vaccination.

BACKGROUND: The antitumor effects of external beam radiation therapy (EBRT) are mediated, in part, by an immune response. We have reported that a single fraction of 12 Gy EBRT combined with intratumoral anti-GD2 hu14.18-IL2 immunocytokine (IC) generates an effective in situ vaccine (ISV) against GD2-positive murine tumors. This ISV is effective in eradicating single tumors with sustained immune memory; however, it does not generate an adequate abscopal response against macroscopic distant tumors. Given the immune-stimulatory capacity of radiation therapy (RT), we hypothesized that delivering RT to all sites of disease would augment systemic antitumor responses to ISV. METHODS: We used a syngeneic B78 murine melanoma model consisting of a 'primary' flank tumor and a contralateral smaller 'secondary' flank tumor, treated with 12 Gy EBRT and intratumoral IC immunotherapy to the primary and additional EBRT to the secondary tumor. As a means of delivering RT to all sites of disease, both known and occult, we also used a novel alkylphosphocholine analog, NM600, conjugated to 90Y as a targeted radionuclide therapy (TRT). Tumor growth, overall survival, and cause of death were measured. Flow cytometry was used to evaluate immune population changes in both tumors. RESULTS: Abscopal effects of local ISV were amplified by delivering as little as 2-6 Gy of EBRT to the secondary tumor. When the primary tumor ISV regimen was delivered in mice receiving 12 Gy EBRT to the secondary tumor, we observed improved overall survival and more disease-free mice with immune memory compared with either ISV or 12 Gy EBRT alone. Similarly, TRT combined with ISV resulted in improved overall survival and a trend towards reduced tumor growth rates when compared with either treatment alone. Using flow cytometry, we identified an influx of CD8+ T cells with a less exhausted phenotype in both the ISV-targeted primary and the distant secondary tumor following the combination of secondary tumor EBRT or TRT with primary tumor ISV. CONCLUSIONS: We report a novel use for low-dose RT, not as a direct antitumor modality but as an immunomodulator capable of driving and expanding antitumor immunity against metastatic tumor sites following ISV.

The Gender of the Sender: Assessing Gender Biases of Greetings in Patient Portal Messages.

Purpose: The purpose of the study was to determine if the use of professional titles in patient electronic health record (EHR) messages varied by gender of the physician receiving the message and gender of the patient sending the message. Methods: We conducted a retrospective observational study evaluating 285,744 messages for a patient's greeting to their physician. Logistic regression mixed effects models were fit to estimate the relationship between title use and gender. Results: Female physicians received 189,442 (66%), and female patients sent 183,579 (64%) messages. Female physicians received an average of 1754 messages each (sd = 1615, median [IQR] = 1624 [255-3040]), which was significantly more than the average 1235 messages for males (sd = 1527, median [IQR] = 385 [103-1857], Mann-Whitney-Wilcoxon p-value = 0.006). Female patients were more likely to send messages using professional titles (OR = 1.37, CI = 1.28-1.47, p < 0.001). Female physicians were no more likely than male physicians to receive professional titles (OR = 1.06, CI = 0.89-1.27, p = 0.500). Conclusions: Female physicians received significantly more EHR messages than men, and female patients were more likely to use a professional title when addressing their physician, regardless of gender. Across all patients, physician gender did not influence the rate of professional title used.

Characteristics and context of fentanyl test strip use among syringe service clients in southern Wisconsin.

BACKGROUND: Fentanyl adulteration of illicit drugs is a major driver of opioid-involved overdose in the USA. Fentanyl test strips are increasingly used by people who use drugs to check for fentanyl. However, little is known about factors that influence test strip use in this population. METHODS: In this mixed-methods study employing semi-structured open-ended interviews (n = 29) and a structured survey (n = 341), we examined characteristics associated with test strip use, characteristics of test strip use, and situational, logistical and psychosocial factors influencing test strip use. Respondents were recruited from a syringe service program in southern Wisconsin. Bivariate tests of association and multivariable logistic regression examined the relationship between respondent characteristics and test strip use. Summary statistics were used to describe how situational, logistical and psychosocial factors impact test strip use. RESULTS: Most respondents were male (59.6%), non-Hispanic white (77.4%), young (mean 35.7 years), reported heroin as their primary drug (70.7%), injection as their primary route (87.9%), and use ≥ 3 times daily (78.6%). In multivariable models, site, race and ethnicity, drug of choice, and seeking fentanyl were associated with test strip use. Among test strip users, 36.5% use them most of the time or more and 80.6% get positive results half the time or more. Among individuals reporting heroin, fentanyl, methamphetamine, or cocaine or crack cocaine at least once per month, 99.1%, 56.8%, 42.2%, and 55.7% reported testing these drugs, respectively. Test strip use is supported by information from suppliers, regular transportation, diverse distribution locations, recommendations from harm reduction staff, and having a safe or private place to use. CONCLUSIONS: We found that individuals who use fentanyl test strips are more often non-Hispanic white, use heroin, and seek drugs with fentanyl relative to individuals without test strip use. Findings confirm high fentanyl penetration in the Wisconsin drug supply. Low rates of stimulant testing suggest inadequate awareness of fentanyl penetration. Findings support outreach to key populations, increased diversity of distributing locations, efforts to correct misperceptions about drug wasting, emphasis on pre-consumption testing, and the importance of adjunct behaviors to prevent overdose given high rates of intentional fentanyl use.

Obesity and "obesity-related" cancers: are there body mass index cut-points?

BACKGROUND: Despite compelling links between excess body weight and cancer, body mass index (BMI) cut-points, or thresholds above which cancer incidence increased, have not been identified. The objective of this study was to determine if BMI cut-points exist for 14 obesity-related cancers. SUBJECTS/METHODS: In this retrospective cohort study, patients 18-75 years old were included if they had ≥2 clinical encounters with BMI measurements in the electronic health record (EHR) at a single academic medical center from 2008 to 2018. Patients who were pregnant, had a history of cancer, or had undergone bariatric surgery were excluded. Adjusted logistic regression was performed to identify cancers that were associated with increasing BMI. For those cancers, BMI cut-points were calculated using adjusted quantile regression for cancer incidence at 80% sensitivity. Logistic and quantile regression models were adjusted for age, sex, race/ethnicity, and smoking status. RESULTS: A total of 7079 cancer patients (mean age 58.5 years, mean BMI 30.5 kg/m2) and 270,441 non-cancer patients (mean age 43.8 years, mean BMI 28.8 kg/m2) were included in the study. In adjusted logistic regression analyses, statistically significant associations were identified between increasing BMI and the incidence of kidney, thyroid, and uterine cancer. BMI cut-points were identified for kidney (26.3 kg/m2) and uterine (26.9 kg/m2) cancer. CONCLUSIONS: BMI cut-points that accurately predicted development kidney and uterine cancer occurred in the overweight category. Analysis of multi-institutional EHR data may help determine if these relationships are generalizable to other health care settings. If they are, incorporation of BMI into the screening algorithms for these cancers may be warranted.

Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma.

BACKGROUND: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( c ombination a daptive- i nnate immunotherapy r egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. METHODS: Mice bearing GD2-expressing 9464D-GD2 tumors were treated with CAIR (external beam radiotherapy, hu14.18-IL2 immunocytokine, CpG, anti-CD40, and anti-CTLA4) and tumor growth and survival were tracked. Depletion of specific immune cell lineages, as well as testing in immunodeficient R2G2 mice, were used to determine the populations necessary for treatment efficacy. Induction of MHC-I expression in 9464D-GD2 cells in response to interferon-γ (IFN-γ) and CAIR was measured in vitro and in vivo, respectively, by flow cytometry and quantitative real-time PCR. A cell line with IFN-γ-inducible MHC-I expression (9464D-GD2-I) was generated by transfecting a subclone of the parental cell line capable of expressing MHC-I with GD2 synthase and was used in vivo to assess the impact of MHC-I expression on responsiveness to CAIR. RESULTS: CAIR cures some mice bearing small (50 mm3) but not larger (100 mm3) 9464D-GD2 tumors and these cured mice develop weak memory responses against tumor rechallenge. Early suppression of 9464D-GD2 tumors by CAIR does not require T or natural killer (NK) cells, but eventual tumor cures are NK cell dependent. Unlike the parental 9464D cell line, 9464D-GD2 cells have uniformly very low MHC-I expression at baseline and fail to upregulate expression in response to IFN-γ. In contrast, 9464D-GD2-I upregulates MHC-I in response to IFN-γ and is less responsive to CAIR. CONCLUSION: Treatment with CAIR cures 9464D-GD2 tumors in a NK cell dependent manner and induction of MHC-I by tumors cells was associated with decreased efficacy. These results demonstrate that the early tumor response to this regimen is T and NK cell independent, but that NK cells have a role in generating lasting cures in the absence of MHC-I expression by tumor cells. Further strategies to better inhibit tumor outgrowth in this setting may require further NK activation or the ability to engage alternative immune effector cells.

Psychometric validation of the AOSL scale using confirmatory factor analysis: A nationally representative sample.

BACKGROUND: The opioid overdose epidemic has worsened during the COVID-19 pandemic. Recent data revealed a 28.5% increase in drug-related overdose deaths from 2019 to 2020. Adolescents often misuse family members' and friends' prescription opioid medications. Furthermore, adolescents may not possess the knowledge or understanding to safely manage opioid medications. There is a need for a validated scale to effectively measure adolescents' opioid misuse knowledge, attitudes, and interest in learning about prescription opioid safety. OBJECTIVE: The purpose of this study was to validate the Adolescent Opioid Safety and Learning (AOSL) scale with a nationally representative sample of adolescents and confirm the factor structure of the scale using confirmatory factor analysis (CFA). METHODS: Adolescent participants (aged 13-18 years) completed the 16-item AOSL scale in Qualtrics from November to December 2020. A total of 774 responses were analyzed. A CFA was performed to determine the fit of the data to the 4-factor model proposed by a prior exploratory factor analysis of the AOSL scale. Fit was assessed using the chi-square test, comparative fit index (CFI), Tucker-Lewis index (TLI), and root mean-squared error of approximation (RMSEA). RESULTS: Participants were 50% male and 62% white non-Hispanic. The CFI was 0.984, TLI was 0.980, and RMSEA was 0.048 ([95% CI 0.041-0.054], P-value that RMSEA ≤ 0.05 = 0.712). The chi-square test results were χ2 = 268.752 on 98 degrees of freedom (P < 0.001). Cronbach's alpha, a measure of internal consistency, was high within each factor. CFA indicated good fit of the current study's data to the 4-factor model. CONCLUSION: We found the AOSL scale measures adolescents' knowledge of opioid misuse, knowledge of opioid harm, interest in learning about prescription opioids, and likelihood to practice misuse behaviors. This scale can help researchers understand adolescent perceptions and opinions about opioid safety.

OB-Newborn TEACH Cards: A Curricular Tool for Maternal-Child Rotations That Influences Patient Care.

Introduction: Evidence-based medicine (EBM) teaching is most successful when integrated with patient care, but finding time for teaching on inpatient rotations is difficult. Obstetrics (OB)-Newborn TEACH (Teaching Evidence-based medicine And Clinical topics in the Hospital) Cards is a curricular tool for efficient teaching sessions on maternity care rotations. We evaluated the impact of OB-Newborn TEACH Cards on resident EBM attitudes and skills, exposure to clinical topics, and patient management. Methods: OB-Newborn TEACH Cards includes 56 cards on obstetrics and newborn topics with background and foreground discussion questions. Residents on a family medicine maternal-child service completed pre- and postrotation surveys to assess the cards' impact on EBM attitudes and skills. Faculty and residents also completed point-of-care surveys to assess the self-reported influence on management decisions. Results: Of 24 potential resident participants, 58% completed pre- and postrotation surveys, which showed significant increase in perceived EBM skills like applying evidence to a clinical scenario (P=.04), but a decrease in reported attitudes that EBM is realistic (P=.028) and useful (P=.025). Residents agreed the cards exposed them to a variety of topics. Point-of-care surveys (n=58) indicated that 57% of the time respondents used a card to learn about a topic not related to a specific patient. When used to learn about specific patients, the cards influenced self-reported patient care 44% of the time. Conclusion: OB-Newborn TEACH Cards are a promising inpatient teaching tool for improving perceived EBM clinical application, exposing residents to maternal-child topics, and influencing patient care decisions.

Short-course neoadjuvant in situ vaccination for murine melanoma.

BACKGROUND: Surgical resection remains an important component of multimodality treatment for most solid tumors. Neoadjuvant immunotherapy has several potential advantages, including in-situ tumor vaccination and pathologic assessment of response in the surgical specimen. We previously described an in-situ tumor vaccination strategy in melanoma using local radiation (RT) and an intratumoral injection of tumor-specific anti-GD2 immunocytokine (IT-IC). Here we tested whether neoadjuvant in-situ tumor vaccination using anti-GD2 immunocytokine and surgical resection, without RT, could generate immunologic memory capable of preventing recurrence or distant metastasis. METHODS: Mice bearing GD2 expressing B78 melanoma tumors were treated with neoadjuvant radiation, IT-IC, or combined RT + IT-IC. Surgical resection was performed following neoadjuvant immunotherapy. Immune infiltrate was assessed in the resection specimens. Mice were rechallenged with either B78 contralateral flank tumors or pulmonary seeding of non-GD2 expressing B16 melanoma metastasis induced experimentally. Rejection of rechallenge in mice treated with the various treatment regimens was considered evidence of immunologic memory. RESULTS: Neoadjuvant IT-IC and surgical resection resulted in increased CD8 T cell infiltration, a higher CD8:regulatory T cell ratio, and immunologic memory against contralateral flank rechallenge. The timing of resection did not significantly impact the development of memory, which was present as early as the day of surgery. There was less local wound toxicity with neoadjuvant IT-IC compared with neoadjuvant RT +IT IC. Neoadjuvant IT-IC and resection resulted in the rejection of B16 lung metastasis in a CD4 T cell dependent manner. CONCLUSIONS: Neoadjuvant IT-IC generates immunologic memory capable of preventing distant metastasis despite limited efficacy against large primary melanoma tumors. By combining neoadjuvant tumor vaccination and surgery, the toxicity of local RT was avoided. These preclinical data support further investigation regarding the use of neoadjuvant IT-IC in patients with melanoma at high risk for occult distant disease.

Reduction in Medication Refill Encounters Through Primary Care Redesign Workflow Changes.

With a goal of improving efficiency and reducing workload outside of visits, we sought to examine a primary care redesign process aimed at reducing refill requests made outside of office visits. Data on the number of refill encounters per panel member were collected at 17 clinics before, during, and after the implementation of a redesign process. There was an initial reduction in the number of medication refill encounters, and the rate of refill encounters continued to decline following implementation. Variation across clinic contexts suggests that redesign processes may need to be tailored for different settings to optimize effectiveness.

Examining adolescents' opioid knowledge and likelihood to utilize an educational game to promote medication safety.

BACKGROUND: Adolescents' knowledge on opioids is seldom studied, despite the fact young people are one of the groups most affected by the opioid crisis within the United States. There is a need to understand adolescents' perceptions about opioid misuse and safety to create the necessary tools to educate adolescents on safe opioid use. OBJECTIVE: This study sought to understand adolescents' knowledge and perceptions of opioid use and safety as well as their receptiveness to using an educational game for improving medication safety knowledge. METHODS: A 67-item survey was developed to assess adolescents' opioid perceptions, knowledge, and the likelihood of an educational game to enhance their opioid medication safety. A nationally representative sample of US adolescents aged 12 to 18 were recruited via a Qualtrics participant panel to complete the online survey from October through November 2020. Survey questions were grouped into 10 categories to represent key concepts and summarized into concept scores. Concepts were described through means, median, and range as well as percent correct for individual questions. Differences between groups were assessed using Kruskal-Wallis tests. Concept scores and their relation to the participant's age were described by the Pearson's correlation coefficient and the linear model coefficient. RESULTS: A total of 592 responses were analyzed. Male and older participants reported greater perceived opioid knowledge than females. White participants reported higher rates of perceived opioid knowledge, behavioral intent, and knowledge of safe medication disposal than any other racial group. About 80% of participants were receptive to the use of an educational game to increase their opioid safety knowledge. CONCLUSIONS: There are discrepancies in adolescents' knowledge on opioid safety and harm amongst genders, race, and age. Study findings support the use of an educational game to increase adolescents' opioid knowledge. Future studies should design an educational game intended for a diverse audience.

The Influence of Sensation Level on Speech-Evoked Envelope Following Responses.

OBJECTIVES: To evaluate sensation level (SL)-dependent characteristics of envelope following responses (EFRs) elicited by band-limited speech dominant in low, mid, and high frequencies. DESIGN: In 21 young normal hearing adults, EFRs were elicited by 8 male-spoken speech stimuli-the first formant, and second and higher formants of /u/, /a/ and /i/, and modulated fricatives, /∫/ and /s/. Stimulus SL was computed from behaviorally measured thresholds. RESULTS: At 30 dB SL, the amplitude and phase coherence of fricative-elicited EFRs were ~1.5 to 2 times higher than all vowel-elicited EFRs, whereas fewer and smaller differences were found among vowel-elicited EFRs. For all stimuli, EFR amplitude and phase coherence increased by roughly 50% for every 10 dB increase in SL between ~0 and 50 dB. CONCLUSIONS: Stimulus and frequency dependency in EFRs exist despite accounting for differences in audibility of speech sounds. The growth rate of EFR characteristics with SL is independent of stimulus and its frequency.

Abdominal fellowship-trained versus generalist radiologist accuracy when interpreting MR and CT for the diagnosis of appendicitis.

OBJECTIVES: To compare the diagnostic accuracy of generalist radiologists working in a community setting against abdominal radiologists working in an academic setting for the interpretation of MR when diagnosing acute appendicitis among emergency department patients. METHODS: This observational study examined MR image interpretation (non-contrast MR with diffusion-weighted imaging and intravenous contrast-enhanced MR) from a prospectively enrolled cohort at an academic hospital over 18 months. Eligible patients had an abdominopelvic CT ordered to evaluate for appendicitis and were > 11 years old. The reference standard was a combination of surgery and pathology results, phone follow-up, and chart review. Six radiologists blinded to clinical information, three each from community and academic practices, independently interpreted MR and CT images in random order. We calculated test characteristics for both individual and group (consensus) diagnostic accuracy then performed Chi-square tests to identify any differences between the subgroups. RESULTS: Analysis included 198 patients (114 women) with a mean age of 31.6 years and an appendicitis prevalence of 32.3%. For generalist radiologists, the sensitivity and specificity (95% confidence interval) were 93.8% (84.6-98.0%) and 88.8% (82.2-93.2%) for MR and 96.9% (88.7-99.8%) and 91.8% (85.8-95.5%) for CT. For fellowship-trained radiologists, the sensitivity and specificity were 96.9% (88.2-99.5%) and 89.6% (82.8-94%) for MR and 98.4% (90.5-99.9%) and 93.3% (87.3-96.7%) for CT. No statistically significant differences were detected between radiologist groups (p = 1.0, p = 0.53, respectively) or when comparing MR to CT (p = 0.21, p = 0.17, respectively). CONCLUSIONS: MR is a reliable, radiation-free imaging alternative to CT for the evaluation of appendicitis in community-based generalist radiology practices. KEY POINTS: • There was no significant difference in MR image interpretation accuracy between generalist and abdominal fellowship-trained radiologists when evaluating sensitivity (p = 1.0) and specificity (p = 0.53). • There was no significant difference in accuracy comparing MR to CT imaging for diagnosing appendicitis for either sensitivity (p = 0.21) or specificity (p = 0.17). • With experience, generalist radiologists enhanced their MR interpretation accuracy as demonstrated by improved interpretation sensitivity (OR 2.89 CI 1.44-5.77, p = 0.003) and decreased mean interpretation time (5 to 3.89 min).

Does a Change in Physician Compensation Lead to Changes in Care Delivery in Family Medicine Clinics?

BACKGROUND AND OBJECTIVES: Many highly capitated systems still pay physicians based on relative value units (RVU), which may lead to excessive office visits. We reviewed electronic health records from the family medicine clinic panel members of 97 physicians and 42 residents to determine if a change from RVUs to panel-based compensation influenced care delivery as defined by the number of office visits and telephone contacts per panel member per month. METHODS: A retrospective analysis of the electronic health records of patients seen in 4 residency training clinics, 10 community clinics, and 4 regional clinics was conducted. We assessed face-to-face care delivery and telephone call volume for the clinics individually and for the clinics pooled by clinic type from 1 year before to at least 1 year after the change. RESULTS: Change in physician compensation was not found to have an effect on office visits or telephone calls per panel member per month when pooled by clinic categories. Some significant effects were seen in individual clinics without any clear patterns by clinic size or type. CONCLUSIONS: Change in physician compensation was not a key driver of care delivery in family medicine clinics. Understanding changes in care delivery may require looking at a broad array of system, physician, and patient factors.

Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models.

Introduction: Combining CpG oligodeoxynucleotides with anti-OX40 agonist antibody (CpG+OX40) is able to generate an effective in situ vaccine in some tumor models, including the A20 lymphoma model. Immunologically "cold" tumors, which are typically less responsive to immunotherapy, are characterized by few tumor infiltrating lymphocytes (TILs), low mutation burden, and limited neoantigen expression. Radiation therapy (RT) can change the tumor microenvironment (TME) of an immunologically "cold" tumor. This study investigated the effect of combining RT with the in situ vaccine CpG+OX40 in immunologically "cold" tumor models. Methods: Mice bearing flank tumors (A20 lymphoma, B78 melanoma or 4T1 breast cancer) were treated with combinations of local RT, CpG, and/or OX40, and response to treatment was monitored. Flow cytometry and quantitative polymerase chain reaction (qPCR) experiments were conducted to study differences in the TME, secondary lymphoid organs, and immune activation after treatment. Results: An in situ vaccine regimen of CpG+OX40, which was effective in the A20 model, did not significantly improve tumor response or survival in the "cold" B78 and 4T1 models, as tested here. In both models, treatment with RT prior to CpG+OX40 enabled a local response to this in situ vaccine, significantly improving the anti-tumor response and survival compared to RT alone or CpG+OX40 alone. RT increased OX40 expression on tumor infiltrating CD4+ non-regulatory T cells. RT+CpG+OX40 increased the ratio of tumor-infiltrating effector T cells to T regulatory cells and significantly increased CD4+ and CD8+ T cell activation in the tumor draining lymph node (TDLN) and spleen. Conclusion: RT significantly improves the local anti-tumor effect of the in situ vaccine CpG+OX40 in immunologically "cold", solid, murine tumor models where RT or CpG+OX40 alone fail to stimulate tumor regression.