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Burnout in healthcare providers begins early, with about half of medical students experiencing symptoms of burnout, and as many as one-quarter experiencing depression. While organizational, systemic-level changes certainly contribute to mitigation, organizationally sponsored individual-level changes may also play a significant role. Although the nature of the burnout epidemic and its impact on trainee wellness is fairly well understood, and interventions have been studied, there remains a gap in the empirical research examining the impact of the arts on medical student well-being.We designed a convergent mixed methods study to evaluate whether a 9-month course for fourth-year medical students called Art as Self Care (AASC) would help trainees develop habits that supported their well-being. An online survey was used to collect data at the beginning and end of each academic year on two consecutive cohorts of students. A focus group explored students' experience with and perceptions about the course.Qualitative results indicated that the AASC course provided positive distraction that is calming and allowed students to shift focus from the stresses of daily medical school life. Our quantitative results suggest that art might provide a slight protective effect in medical students: whereas 22% of the non-AASC students saw a worsening of their psychological distress across the fourth year of medical school, this was observed in only 13% of the AASC students.Our study presents pilot and feasibility data to better inform future research and practice around the use of art to support medical student well-being.The online version contains supplementary material available at 10.1007/s40670-022-01604-y.

Background Underserved and minority populations are often reluctant to engage in advance care planning and/or research often due to distrust in healthcare and/or research institutions. Aim To determine if use of a community-based delivery model can facilitate recruitment of individuals from underserved communities in research about advance care planning. Design Recruitment data are presented from a prospective, mixed methods observational cohort study that examined the feasibility and preliminary efficacy of a community-based delivery model involving an end-of-life conversation game to motivate participants to complete advance care planning behaviors. Event attendance and research participation data are reported. Setting/participants Game events were held in community venues in 27 states across the US in 2018-2019. The model involved leveraging existing social networks to recruit attendees and research participants to community game day events. Attendees were eligible for research if they were adults who read/spoke English. Results 1,122 individuals attended events at 53 sites. Participants generally reported low income (48% reported $30,000 annual income). At sites with research assistants, there was a 90% consent rate (92% were Black). At community outreach sites, 45% agreed to a follow-up research phone call (49% were Black). Conclusions Use of the community-based delivery model successfully engaged undeserved communities in a research-based advance care planning related community outreach event. This model may be useful for overcoming underserved and minority populations’ skepticism and distrust of healthcare and research that is a common barrier to progress in health agendas, especially advance care planning.

Introduction: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. Methods: Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (N = 27) and HC participants (N = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. Results: A significant interaction (F = 2.74, df = 5, and p = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (p = 0.01). Conclusion: Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.

Purpose To explore public knowledge, understanding of public health recommendations, perceptions, and trust in information sources related to COVID-19. Methods A cross-sectional survey of central Pennsylvanian adults evaluated self-reported knowledge, and a convergent, mixed methods design was used to assess beliefs about recommendations, intended behaviors, perceptions, and concerns related to infectious disease risk, and trust of information sources. Results The survey was completed by 5,948 adults. The estimated probability of correct response for the basic knowledge score, weighted with confidence, was 0.79 (95% CI, 0.79-0.80). Knowledge was significantly higher in patients with higher education and nonminority race. While the majority of respondents reported that they believed following CDC recommendations would decrease the spread of COVID-19 in their community and intended to adhere to them, only 65.2% rated social isolation with the highest level of belief and adherence. The most trusted information source was federal public health websites (42.8%). Qualitative responses aligned with quantitative data and described concerns about illness, epidemiologic issues, economic and societal disruptions, and distrust of the executive branch's messaging. The survey was limited by a lack of minority representation, potential selection bias, and evolving COVID-19 information that may impact generalizability and interpretability. Conclusions Knowledge about COVID-19 and intended adherence to behavioral recommendations were high. There was substantial distrust of the executive branch of the federal government, however, and concern about mixed messaging and information overload. These findings highlight the importance of consistent messaging from trusted sources that reaches diverse groups.

Background: Family members of intensive care unit (ICU) patients often report poor communication, feeling unprepared for ICU family meetings, and poor psychological outcomes after decision-making. The objective of this study was to create a tool to prepare families for ICU family meetings and assess feasibility of using Communication Quality Analysis (CQA) to measure communication quality of family meetings. Methods: This observational study was conducted at an academic tertiary care center in Hershey, PA from March 2019 to 2020. Phase 1a involved conceptual design. Phase 1b entailed acceptability testing of 2 versions of the tool (text-only, comic) with 9 family members of non-capacitated ICU patients; thematic analysis of semi-strucutred interviews was conducted. Phase 1c assessed feasibility of applying CQA to audio-recorded ICU family meetings (n = 17); 3 analysts used CQA to assess 6 domains of communication quality. Wilcoxon Signed Rank tests were used to interpret CQA scores. Results: Four themes emerged from Phase 1b interviews: participants 1) found the tool useful for meeting preparation and organizing thoughts, 2) appreciated emotional content, 3) preferred the comic form (67%), and 4) had indifferent or negative perceptions about specific elements. In Phase 1c, clinicians scored higher on the CQA content and engagement domains; family members scored higher on the emotion domain. CQA scores in the relationship and face domains had the lowest quality ratings. Conclusions: Let’s Talk may help families become better prepared for ICU family meetings. CQA provides a feasible approach to assessing communication quality that identifies specific areas of strengths and weaknesses in communication.

BACKGROUNDThe U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the likely effects of this regulation in smokers with affective disorders.METHODSIn a randomized controlled trial conducted at two sites (Penn State Hershey and Massachusetts General Hospital, Boston) 188 adult smokers with a current or lifetime anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) cigarettes, or Reduced Nicotine Content (RNC) cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms.RESULTSAfter switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, the RNC group had significantly lower plasma cotinine (metabolite of nicotine), urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence. There were no significant effects on psychiatric symptoms. At the end of the 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking (18% RNC v 4% UNC, p=0.004).CONCLUSIONReducing nicotine content in cigarettes to very low levels reduces toxicant exposure and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health.Trial registrationTRN: NCT01928758, registered August 21, 2013

Purpose: To compare COVID-19 related knowledge, perceptions, and preferred information sources between healthcare workers and non-healthcare workers. Design: Cross-sectional survey. Setting: Web-based. Subjects: Convenience sample of Pennsylvanian adults. Measures: Primary outcomes were binary responses to 15 COVID-19 knowledge questions weighted by a Likert scale assessing response confidence. Analysis: Generalized linear mixed-effects models to assess comparisons between clinical decision makers (CDM), non-clinical decision makers working in healthcare (non-CDM) and non-healthcare workers (non-HCW). Results: CDMs (n = 91) had higher overall knowledge than non-CDMs (n = 854; OR 1.81 [1.51, 2.17], p < .05). Overall knowledge scores were not significantly different between non-CDMs (n = 854) and non-HCW (n = 4,966; OR 1.03 [0.97, 1.09], p > .05). Conclusion: The findings suggest a need for improved education about COVID-19 for healthcare workers who are not clinical decision makers, as they play key roles in patient perceptions and compliance with preventive medicine during primary care visits.

Introduction The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC). Methods A 33 week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. Results The RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference −137 ng/mL; 95% CI −172, −102). The RNC group smoked fewer CPD (−4.1; 95% CI −6.44, −1.75) and had lower carbon monoxide levels (−4.0 ppm; 95% CI −7.7, −0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%). Conclusions This study supports a VLNC standard in cigarettes. Implications Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.

BACKGROUND: African Americans have low engagement in advance care planning (ACP). This has been attributed to healthcare distrust and skepticism about ACP. A better understanding of these attitudes is needed to address health disparities related to end-of-life care. OBJECTIVE: To explore the ACP-related values and beliefs of diverse African American communities across the USA and then the perceived value of an inexpensive end-of-life conversational game. DESIGN: Prospective, convergent, mixed methods cohort study involving fifteen underserved, African American communities across the USA. PARTICIPANTS: Of the 428 who attended events at purposively sampled sites, 90% consented to the research; 37% participated in one of 15 focus groups (n = 141). INTERVENTION: An end-of-life conversation game, played in groups of 4–6. MAIN MEASURES: The validated, 7-item ACP values and beliefs questionnaire (scaled 7 = least skeptical, 49 = most skeptical) was administered pre-game. Post-game focus groups explored perceptions about ACP and the intervention. KEY RESULTS: Participants had positive attitudes (low skepticism) about ACP with a median score of 12.00 (7.00, 20.00). Values and beliefs did not significantly differ by geographical region; however, rural areas were observed to be slightly more skeptical than urban areas (median score 14.00 vs. 11.00, p = 0.002). Themes from focus groups converged with survey data showing participants valued the ACP process and consider further engagement in ACP to be worthwhile. Subthemes emphasized the need for and value of ACP. CONCLUSIONS: Skepticism about ACP may contribute to low rates of ACP engagement in underserved African American communities. The positive attitudes uncovered in our study either negate previous findings or suggest reduced skepticism. TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov (NCT03456921) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06224-z) contains supplementary material, which is available to authorized users.

Background: Few studies have examined prostate cancer incidence and aggressiveness in urban-rural Appalachian populations. We examined these rates in urban-rural Appalachia and non-Appalachia Pennsylvania (PA), and the association between these areas and more aggressive prostate cancer at diagnosis. Methods: Men, ages ≥ 40 years with a primary prostate cancer diagnosis, were identified from the 2004–2014 Pennsylvania Cancer Registry. Age-adjusted incidence rates for prostate cancer and more aggressive prostate cancer at diagnosis were calculated by urban-rural Appalachia status. Multivariable Poisson regressions were conducted. Multiple logistic regressions were used to examine the association between the geographic areas and more aggressive prostate cancer, after adjusting for confounders. Results: There were 94,274 cases, ages 40–105 years, included. Urban non-Appalachia had the highest 2004–2014 age-adjusted incidence rates of prostate cancer and more aggressive prostate cancer (293.56 and 96.39 per 100,000 men, respectively) and rural Appalachia had the lowest rates (256.48 and 80.18 per 100,000 men, respectively). Among the cases, urban Appalachia were more likely [OR = 1.12; 95% confidence interval (CI) = 1.08–1.17] and rural Appalachia were less likely (OR = 0.92; 95% CI = 0.87–0.97) to have more aggressive prostate cancer at diagnosis compared with urban non-Appalachia. Conclusions: Lower incidence rates and the proportion of aggressive disease in rural Appalachia may be due to lower prostate cancer screening rates. More aggressive prostate cancer at diagnosis among the cases in urban Appalachia may be due to exposures that are prevalent in the region. Impact: Identifying geographic prostate cancer disparities will provide information to design programs aimed at reducing risk and closing the disparity gap.

Background To assess: (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania. Methods Prostate cancer survivors ages ≥40 years were identified from the 2004‐2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC‐specific mortality. County‐level data from the Pennsylvania BRFSS were used to estimate cancer‐related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates. Results There were 90 694 PCS ages 40‐105 years (mean age = 66.19 years, SD = 9.25) included. Most were non‐Hispanic white men (83%). Prostate cancer survivors ≥75 years were least likely to receive any treatment but men ages 65‐74 were more likely to receive combined therapies (OR = 1.47; 95% CI 1.28, 1.69) vs PCS ages 40‐54 years, controlling for covariates. Prostate cancer survivors 55‐75+ with aggressive PC who received any treatment vs no definitive treatment had significantly reduced mortality. Men from counties with high obesity and smoking rates were significantly less likely to receive any treatment than men living in counties with lower rates of these risk factors. Prostate cancer survivors who lived in counties with high rates of physical inactivity and had high rates of sufficient FV consumption were slightly more likely to receive cancer treatment vs no definitive treatment compared to men who lived in counties with high rates of physical activity and lower FV consumption. Conclusions We observed a general age‐related decline in receipt of treatment. Prostate cancer survivors ages ≥75 years were significantly less likely to get any cancer treatment compared to younger PCS. However, most men with more aggressive disease who received any treatment had greatly reduced PC mortality, regardless of age. Considering environmental/behavioral risk factors may attenuate PC risk and inform treatment options., We analyzed prostate cancer registry data for >90 000 men ages 40‐105 to understand age‐related associations with disease aggressiveness, treatment and potential role of environmental/behavioral risk factors in understanding likelihood of treatment recommendations and impact on mortality. Men older than 75 years were more likely to have aggressive disease but less likely to receive any treatment. The oldest men also had the greatest survival benefits from any treatment. We also provide insight on whether where you live impacts your treatment and ultimate survival.

Children’s hospitals are discharging patients to home with increasingly complex outpatient needs, making safe transitions of care (ToCs) of vital importance. Our study involved a survey of both outpatient providers and pediatric hospitalists associated with our medical center to better describe providers’ views on the ToC process. The survey included questions assessing views on patient care responsibilities, resource availability, our hospitalist-run postdischarge clinic (PDC), and comfort with telemedicine. Our hospitalists generally believed that primary care providers (PCPs) did not have adequate access to important ToC elements, whereas PCPs felt their access was adequate. Both provider types felt it was the inpatient team’s responsibility to manage patient events between discharge and PCP follow-up and that a hospitalist-run PDC may reduce interim emergency room visits. This study challenges perceptions about the ToC process in children and describes a generalizable approach to assessing provider perceptions surrounding the ToC within individual health systems.

Childhood asthma derives from complex host-environment interactions occurring in the perinatal and infant period, a critical time for lung development. Sphingolipids are bioactive molecules consistently implicated in the pathogenesis of childhood asthma. Genome wide association studies (GWAS) initially identified a link between alleles within the 17q21 asthma-susceptibility locus, childhood asthma, and overexpression of the ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), an inhibitor of de novo sphingolipid synthesis. Subsequent studies of pediatric asthma offer strong evidence that these asthma-risk alleles correlate with early-life aberrancies of sphingolipid homeostasis and asthma. Relationships between sphingolipid metabolism and asthma-related risk factors, including maternal obesity and respiratory viral infections, are currently under investigation. This review will summarize how these perinatal and early life exposures can synergize with 17q21 asthma risk alleles to exacerbate disruptions of sphingolipid homeostasis and drive asthma pathogenesis.

The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of de novo sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis. Children with asthma and 17q21 asthma risk alleles display decreased sphingolipid synthesis in blood cells. Reduced SPT activity results in airway hyperreactivity, a hallmark feature of asthma. 17q21 asthma risk alleles are also linked to childhood infections with human rhinovirus (RV). This study evaluates the interaction of RV with the de novo sphingolipid synthesis pathway, and the alterative effects of concurrent SPT inhibition in SPT-deficient mice and human airway epithelial cells. In mice, RV infection shifted lung sphingolipid synthesis gene expression to a pattern that resembles genetic SPT deficiency, including decreased expression of Sptssa, a small SPT subunit. This pattern was pronounced in lung epithelial cellular adhesion molecule (EpCAM(+)) cells and reproduced in human bronchial epithelial cells. RV did not affect Sptssa expression in lung CD45(+) immune cells. RV increased sphingolipids unique to the de novo synthesis pathway in mouse lung and human airway epithelial cells. Interestingly, these de novo sphingolipid species were reduced in the blood of RV-infected wild-type mice. RV exacerbated SPT deficiency–associated airway hyperreactivity. Airway inflammation was similar in RV-infected wild-type and SPT-deficient mice. This study reveals the effects of RV infection on the de novo sphingolipid synthesis pathway, elucidating a potential mechanistic link between 17q21 asthma risk alleles and rhinoviral infection.

OBJECTIVE: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). METHODS: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. RESULTS: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. CONCLUSIONS: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02272010.

Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA). Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004–2014. Joinpoint analysis was used to evaluate the temporal trend of highly aggressive PC (clinical/pathologic Gleason score ≥ 7 [4 + 3], clinical/pathologic tumor stage ≥ T3, or distant metastasis) and identify change points by race in which annual percent change (APC) was calculated. Logistic regression analyses were used to examine the association between race and highly aggressive PC, after adjusting for covariates with and without spatial dependence. There were 89,133 PC cases, which included 88.7% white and 11.3% black men. The APC of highly aggressive PC was 8.7% from 2011 to 2014 among white men and 3.6% from 2007 to 2014 among black men (p values ≤ 0.01). The greatest odds of having highly aggressive PC among black compared to white men were found in counties where the black male population was ≤ 5.3%. Highly aggressive PC increased for both black and white men in PA between 2004 and 2014. Black men had more aggressive disease, with the greatest odds in counties where the black male population was small. The increase in highly aggressive PC may be due to less screening for PC, resulting in more advanced disease at diagnosis.

The effectiveness of evidence-based guidelines (EBGs) and clinical decision support (CDS) is significantly hampered by widespread clinician resistance to it. Our study was designed to better understand the reasons for this resistance to CDS and explore the factors that drive it.We used a mixed-methods approach to explore and identify the drivers of resistance for CDS among clinicians, including a web-based multispecialty survey exploring clinicians' impressions of the strengths and weaknesses of CDS, two clinician focus groups, and several one-on-one focused clinician interviews in which individual participants were asked to comment on their rationale for choosing imaging utilization that might not be supported by EBGs. Additionally, a unique electronic learning and assessment module known as Amplifire was used to probe clinician knowledge gaps regarding EBGs and CDS.In both the quantitative and qualitative portions of the study, the primary factor driving resistance to CDS was a desire to order studies not supported by EBGs, primarily for the purpose of reducing the clinician's diagnostic uncertainty.Our results suggest that to enhance the effectiveness of CDS, we must first address the issue of clinician discomfort with diagnostic uncertainty and the role of imaging via educational outreach and ongoing radiologist consultation.

During the COVID-19 pandemic, Americans have increasingly relied on internet versus television news. The extent to which this change in health news consumption practice impacts health knowledge is not known. This study investigates the relationship between most trusted information source and COVID-19 knowledge.A cross-sectional online survey was sent to a convenience sample from a list of adults on a central Pennsylvania health system's marketing database 25-31 March 2020. Respondents were grouped by their trusted news sources and comparison of respondent COVID-19 knowledge was made between these groups for 5948 respondents.Those who selected government health websites as their most trusted source were more likely to answer COVID-19 questions correctly than those who selected other internet news sources or television news (OR 1.21,COVID-19 knowledge correlates with trusted news source. To increase public knowledge of COVID-19 in order to maximize information dissemination and compliance with COVID-19-related public health recommendations, those who provide health information should consider use of the public's most trusted sources of information, as well as monitoring and correcting misinformation presented by other sources. Independent content review for accuracy in media may be warranted in public health emergencies to improve knowledge.

We describe the process by which a PICU and a PICU care team were incorporated into a hospital-wide ICU care model during the coronavirus disease 2019 pandemic.A descriptive, retrospective report from a single-center PICU.Twenty-three bed, quaternary PICU, within an 862-bed hospital.Critically ill adults, with coronavirus disease 2019-related disease.ICU care provided by pediatric intensivists with training and support from medical intensivists.Within the context of the institution's comprehensive effort to centralize and systematize care for adults with severe coronavirus disease 2019 disease, the PICU was transitioned to an adult coronavirus disease 2019 critical care unit. Nurses and physicians underwent just-in-time training over 3 days and 2 weeks, respectively. Medical ICU physicians and nurses provided oversight for care and designated hospital-based teams were available for procedures and common adult emergencies. Over a 7-week period, the PICU cared for 60 adults with coronavirus disease 2019-related critical illness. Fifty-three required intubation and mechanical ventilation for a median of 18 days. Eighteen required renal replacement therapy and 17 died.During the current and potentially in future pandemics, where critical care resources are limited, pediatric intensivists and staff can be readily utilized to meaningfully contribute to the care of critically ill adults.

OBJECTIVES: We describe the process by which a PICU and a PICU care team were incorporated into a hospital-wide ICU care model during the coronavirus disease 2019 pandemic. DESIGN: A descriptive, retrospective report from a single-center PICU. SETTING: Twenty-three bed, quaternary PICU, within an 862-bed hospital. PATIENTS: Critically ill adults, with coronavirus disease 2019-related disease. INTERVENTIONS: ICU care provided by pediatric intensivists with training and support from medical intensivists. MEASUREMENTS AND MAIN RESULTS: Within the context of the institution's comprehensive effort to centralize and systematize care for adults with severe coronavirus disease 2019 disease, the PICU was transitioned to an adult coronavirus disease 2019 critical care unit. Nurses and physicians underwent just-in-time training over 3 days and 2 weeks, respectively. Medical ICU physicians and nurses provided oversight for care and designated hospital-based teams were available for procedures and common adult emergencies. Over a 7-week period, the PICU cared for 60 adults with coronavirus disease 2019-related critical illness. Fifty-three required intubation and mechanical ventilation for a median of 18 days. Eighteen required renal replacement therapy and 17 died. CONCLUSIONS: During the current and potentially in future pandemics, where critical care resources are limited, pediatric intensivists and staff can be readily utilized to meaningfully contribute to the care of critically ill adults.

IntroductionAbout half of smokers relight their cigarette, a habit that is a risk factor for chronic bronchitis and possibly lung cancer. Little is known about the characteristics of smokers who relight and their dependence on nicotine. It is unknown whether relighting affects exposure to tobacco smoke constituents. This study examined the characteristics of relighters of usual brand cigarettes and whether relighting affects exposure to selected tobacco smoke constituents.MethodsWe explored relighting status and frequency, using baseline data from 248 adult smokers participating in studies of reduced nicotine cigarettes in relation to demographic and cigarette characteristics, smoking behaviors, nicotine dependence, biomarkers of exposure (exhaled carbon monoxide, blood cotinine), and biomarkers of oxidative stress (ratio of oxidized/reduced glutathione).Results69.4% (n = 172) of subjects reported relighting, and they relit an average of five cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 cigarettes per day (p = .6). Relighting was significantly associated with higher nicotine dependence, use of longer rod cigarettes, older age, lower income, and unemployment. There were no significant associations between relighting and blood cotinine, exhaled carbon monoxide or measures of oxidized/reduced blood glutathione.ConclusionsThe majority of subjects were relighters, who had higher levels of nicotine dependence than non-relighters. Relighters had similar levels of plasma cotinine and exhaled carbon monoxide to non-relighters.ImplicationsNo study has compared the cigarette characteristics and biomarkers of exposure of adult cigarette smokers who relight with those who do not. Relighting behavior was common in our sample and was associated with low income, not currently working, higher nicotine dependence, cigarette rod length, daily cigarette use years, and a lifetime history of depressed mood.

The development of immunotherapies has resulted in significant improvements in survival for children with cancer and congenital blood disorders. The purpose of this review is to guide the recognition and treatment of significant side of effects three increasingly used immunotherapies—T cell-mediated therapies, immune checkpoint inhibitors, and anti-GD2 antibodies. Cytokine release syndrome (CRS) is a cytokine-induced systemic inflammatory state secondary to chimeric antigen receptor T cells (CAR–T cells), a therapy used for relapsed and refractory leukemia. CRS can range from fever and mild flu-like symptoms to cardiopulmonary collapse and neurologic sequelae including encephalitis, seizures, and cerebral edema. Immune check point inhibitors work to redirect the T cell response towards cancer cells and have shown a survival advantage for patients with advanced melanoma. These agents also activate an immune response which can mimic autoimmune disease and cause organ failure and neurologic complications like Guillain–Barre and posterior reversible encephalopathy. Children with high-risk and chemotherapy-resistant neuroblastoma have seen improved survival with the use of anti-GD2, an immunotherapy directed at the highly abundant and conserved GD2 antigen expressed on neuroblastoma cells. Severe pain is the consistently reported side effect of anti-GD2, occurring in an estimated 50% of patients and often requiring narcotic and sedative agents for the duration of therapy. Immunotherapy has become critical to the treatment of previously irremediable diseases like relapsed leukemia and refractory neuroblastoma. The survival advantage offered by these therapies requires an understanding of diagnosis and treatment of their life-threatening toxicities.

© 2017 Elsevier Inc. Characterizing how representations of moral violations are organized, cognitively and neurally, is central to understanding how people conceive and judge them. Past work has identified brain regions that represent morally relevant features and distinguish moral domains, but has not yet advanced a broader account of where and on what basis neural representations of moral violations are organized. With searchlight representational similarity analysis, we investigate where category membership drives similarity in neural patterns during moral judgment of violations from two key moral domains: Harm and Purity. Representations converge across domains in a network of regions resembling the mentalizing network. However, Harm and Purity violation representations respectively converge in different regions: precuneus (PC) and left inferior frontal gyrus (LIFG). Examining substructure within moral domains, Harm violations converge in PC regardless of subdomain (physical harms, psychological harms), while Purity subdomains (pathogen-related violations, sex-related violations) converge in distinct sets of regions – mirroring a dissociation observed in principal-component analysis of behavioral data. Further, we find initial evidence for representation of morally relevant features within these two domain-encoding regions. The present analyses offer a case study for understanding how organization within the complex conceptual space of moral violations is reflected in the organization of neural patterns across the cortex.

Background The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure. The effectiveness of this strategy needs to be demonstrated in different populations whose response to RNC cigarettes might be substantially mediated by personal or environmental factors, such as low socioeconomic status (SES) populations. This study aims to evaluate the response to a reduced nicotine intervention in low SES smokers, as defined here as those with less than 16 years of education, by switching smokers from high nicotine commercial cigarettes to RNC cigarettes. Methods/design Adults (N = 280) who have smoked five cigarettes or more per day for the past year, have not made a quit attempt in the prior month, are not planning to quit, and have less than 16 years of education are recruited into a two-arm, double-blinded randomized controlled trial. First, participants smoke their usual brand of cigarettes for 1 week and SPECTRUM research cigarettes containing a usual amount of nicotine for 2 weeks. During the experimental phase, participants are randomized to continue smoking SPECTRUM research cigarettes that contain either (1) usual nicotine content (UNC) (11.6 mg/cigarette) or (2) RNC (11.6 to 0.2 mg/cigarette) over 18 weeks. During the final phase of the study, all participants are offered the choice to quit smoking with nicotine replacement therapy, continue smoking the research cigarettes, or return to their usual brand of cigarettes. The primary outcomes of the study include retention rates and compliance with using only research cigarettes and no use of other nicotine-containing products. Secondary outcomes are tobacco smoke biomarkers, nicotine dependence measures, smoking topography, stress levels, and adverse health consequences. Discussion Results from this study will provide information on whether low SES smokers can maintain a course of progressive nicotine reduction without increases in incidence of adverse effects. Trial registration ClinicalTrials.gov, NCT01928719. Registered on 21 August 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2038-9) contains supplementary material, which is available to authorized users.

Background Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual- and county-level risk factors. Methods Prostate cancer cases, aged ≥40 years, were identified in the 2004–2014 Pennsylvania Cancer Registry. The 2018 County Health Rankings data and the 2014 U.S. Environmental Protection Agency’s Environmental Quality Index were used to extract county-level data. The accelerated failure time models with spatial frailties for geographical correlations were used to assess prostate cancer-specific mortality rates for Pennsylvania and by the Penn State Cancer Institute (PSCI) 28-county catchment area. Secondary assessment based on estimated spatial frailties was conducted to identify potential health and environmental risk factors for mortality. Results There were 94,274 cases included. The 5-year survival rate in PA was 82% (95% confidence interval, CI: 81.1–82.8%), with the catchment area having a lower survival rate 81% (95% CI: 79.5–82.6%) compared to the non-catchment area rate of 82.3% (95% CI: 81.4–83.2%). Black men, uninsured, more aggressive prostate cancer, rural and urban Appalachia, positive lymph nodes, and no definitive treatment were associated with lower survival. Several county-level health (i.e., poor physical activity) and environmental factors in air and land (i.e., defoliate chemical applied) were associated with higher mortality rates. Conclusions Spatial variations in prostate cancer-specific mortality rates exist in Pennsylvania with a higher risk in the PSCI’s catchment area, in particular, rural-Appalachia. County-level health and environmental factors may contribute to spatial heterogeneity in prostate cancer-specific mortality.

In the United States, the five-year survival rate of colorectal cancer for Latinos is lower than it is for White, non-Latinos. Differences in survival are due, in part, to Latinos being diagnosed at a later stage. An ethnic gap in the use of colorectal cancer screening contributes to the difference in survival. We developed, implemented, and evaluated a targeted colorectal cancer screening intervention to increase colorectal cancer screening uptake by sex, ethnicity, and geography. We measured actual colorectal cancer screening uptake in both arms as a method to determine completion rates. We used a randomized, community-based, participatory design to test the impact of social support (intervention) on completion of a provider-recommended, take-home fecal immunochemical test (FIT) kit screening test among average-risk, urban, and rural Pennsylvania Latino adults age 50 and older not currently adherent to national colorectal cancer screening guidelines (n = 264). Participants in each arm attended a community-based educational program offered at eight sites. Among the 264 participants, 154 (58%) returned a completed usable FIT kit screening test. A higher return rate was observed among participants in the social support arm (66.0%) compared with the control (47.2%). Participants in the social support arm were statistically significant 2.67 times as likely to return a completed FIT kit. Of these, 27 (17.5%) had a positive FIT kit screening test result. The results of this study suggest that social support is an effective method to increase colorectal cancer screening rates among Latinos. Future studies should examine dissemination and implementation of community-based strategies among Latinos that include social support.

Why are we willing to help others? Recent behavioral work on episodic processes (i.e. the ability to represent an event that is specific in time and place) suggests that imagining and remembering scenes of helping a person in need increases intentions to help. Here, we provide insight into the cognitive and neural mechanisms that enhance prosocial intentions via episodic simulation and memory. In Experiment 1, we scanned participants using functional neuroimaging as they imagined and remembered helping episodes, and completed non-episodic control conditions accounting for exposure to the story of need and conceptual priming of helping. Analyses revealed that activity in the medial temporal lobe (MTL) subsystem, as well as the right temporoparietal junction (RTPJ) predicted the effect of conditions on the strength of prosocial intentions. In Experiment 2, we used transcranial magnetic stimulation to disrupt activity in the RTPJ, and better isolate the contribution of MTL subsystem to prosocial intentions. The effect of conditions on willingness to help remained even when activity in the RTPJ was disrupted, suggesting that activity in the MTL subsystem may primarily support this prosocial effect. It seems our willingness to help may be guided, in part, by how easily we can construct imagined and remembered helping episodes.

Research on third-party moral judgments highlights two mechanisms as central to moral judgments of accidental harms: the inference of intent and the perception of harm. However, little is known about how these mechanisms are recruited when people evaluate themselves for harm that they have accidentally caused. Here we explore how a person's perspective — as either actor or observer — influences their moral judgments of accidental harm. We use fMRI to investigate how brain regions involved in the inference of intent and the perception of harm differentially respond when participants either cause (first-person) or observe (third-person) accidental harm. First, we find that people judge their own accidental harms more harshly than they judge others' accidents, and hold themselves more responsible for the unintended harmful outcomes of their choices. Second, we find that regions responding to the first-hand experience of pain are also more sensitive to first-person harms relative to third-person harms, and brain-behavior relationships in a subset of these regions suggest that the tendency to judge oneself more harshly may be supported by a greater sensitivity to the victim's experience of harm. Third, though we find that first-person harms recruit regions for mental state inference to a lesser extent than third-person harms, this difference does not appear to account for the behavioral differences in moral judgment between first-person and third-person harms. The results of this experiment suggest that accidental harms are an important context for broadening our understanding of the relationship between agency, empathy, and moral judgments about the self.

Key Points Question Can a low-cost, easily scaled, end-of-life conversation game motivate underserved African American individuals to engage in advance care planning? Findings This national mixed-methods cohort study reaching 384 underserved African American individuals found that high rates of advance care planning behavior were associated with participation in game events at community venues. Meaning The end-of-life conversation game may be a useful tool for engaging underserved African American communities in advance care planning, a step toward reducing health disparities related to end-of-life care., Importance Less than 25% of African American individuals have completed advance directives and are thus vulnerable to poor end-of-life care. Low-cost interventions are needed to increase engagement in advance care planning (ACP). Objectives To investigate whether an end-of-life conversation game motivates African American attendees to engage in ACP and to assess whether the game is well received and endorsed. Exposures Attendance at an end-of-life conversation game (Hello) played in groups of 4 to 6 participants for 60 minutes. Design, Setting, and Participants Prospective, mixed-methods cohort study conducted from 2018 to 2019 with a 3- to 11-month follow-up interview. Game events were held in 53 community venues across the US; 15 were purposively sampled for onsite research procedures. Of 428 attendees at purposively sampled sites, 386 (90%) consented to research procedures (6 attendees were removed from analysis for protocol deviation). Of 367 attendees who provided accurate contact information, 232 (63%) were contacted, and 220 were included in follow-up analyses. Main Outcomes and Measures The primary outcome was advance directive completion rates after the intervention. Secondary outcomes included rates of other ACP behaviors, ACP engagement, conversation satisfaction and realism, and participants’ Net Promoter Score (a measure of endorsement). Follow-up telephone interviews explored the game experience and relevant ACP behaviors of attendees. Results Of 380 individuals who participated (mean [SD] age, 62.2 [13.8] years; 304 were female [80%], and 348 were [92%] African American), none withdrew because of an adverse event. After the intervention, 91 of 220 attendees (41%) completed a new advance directive; 176 of 220 attendees (80%) discussed end-of-life wishes with loved ones, and 214 of 219 attendees (98%) completed at least 1 ACP behavior. There was a moderate increase in the self-efficacy domain on the ACP Engagement Survey (mean [SD] change from before to after the game, 0.54 [0.98]; P, This national mixed-methods cohort study investigates whether an end-of-life conversation game is well received and endorsed and motivates advance care planning among underserved African American individuals.

Regulations requiring a reduction of the nicotine content in cigarettes to minimally addictive levels could significantly reduce the public health impact of cigarette smoking. Clinical trials evaluating this strategy are ongoing and methods have been developed to use nicotine biomarkers to estimate compliance with use of very low nicotine content cigarettes (VLNCs). To date, these methods have not considered the potential contribution of nicotine absorption from environmental tobacco smoke (ETS) among research participants. This study used data from 100 randomly selected study completers in ongoing clinical trials of VLNCs (50 randomized to Usual Nicotine Content Cigarettes (UNCs) and 50 to VLNCs) to assess the use of plasma cotinine to estimate compliance. Plasma cotinine and smoking behavior were recorded at baseline after 2 weeks smoking UNC cigarettes, and then after 18 weeks of either continuing smoking UNCs or reducing the nicotine content such that the last 6 weeks comprised smoking VLNCs. Plasma cotinine remained stable (267 ng/ml) in the UNC group but reduced to 93 ng/ml in the VLNC group (p 0.01). Compliance with smoking VLNCs was first estimated by comparing the cotinine per cigarette on VLNCs with UNCs after allowing for potential compensatory smoking. We found that 29 (58%) of the VLNC group were compliant. Adjusting for potential ETS exposure estimated 32 (64%) to be compliant. This latter group (n = 32) had a mean plasma cotinine on VLNCs of 7 ng/ml (range = 3-16.4 ng/ml). Adjusting for potential ETS exposure may improve identification of participants who plausibly complied with exclusive VLNC use.

We analyzed data from the 2014-2015 Pennsylvania Youth Tobacco Survey to determine prevalence of tobacco use among middle and high school students. For the first time, questions on current (past 30-day) use of electronic cigarettes (e-cigarettes) were included in the survey. For current use, e-cigarettes were the most commonly used tobacco product among middle school students (2.3%; 95% confidence interval [CI], 1.4%-3.2%), and cigarettes were the most commonly used tobacco product among high school students (11.0%; 95% CI, 8.1%-13.8%). Given the changing landscape of tobacco products, collection of comprehensive data on tobacco use, including frequency, is important for monitoring behaviors among adolescents.

Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products. Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011–2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders. Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers. Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs. Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601–9. ©2018 AACR.

Adhering to standard procedures (impartiality), returning favors (reciprocity) or giving based on individuals' needs (charity) may all be considered moral and/or fair ways to allocate resources. However, these allocation behaviors may be perceived as differently motivated, and their moral evaluation may make different demands on theory of mind (ToM) - the capacity to process information about mental states, including motives. In Studies 1 and 2, we examined participants' moral judgments of allocations based on (1) impartiality, (2) reciprocity, (3) charity and (4) unspecified criteria as depicted in vignettes, as well as participants' perceptions of allocators' motivations. In Study 3, we used functional magnetic resonance imaging to investigate how brain regions for ToM were recruited during moral evaluation of the same vignettes. Reciprocity and charity were processed similarly, in that they recruited ToM regions to the same extent, i.e., precuneus, dorsal and ventral medial prefrontal cortex and left temporoparietal junction (LTPJ). In turn, impartiality and the unspecified condition were processed similarly, recruiting the same ToM regions to a lesser extent. Nevertheless, reciprocity elicited greater activity relative to impartiality and unspecified in the ToM regions of interest. Overall, evaluations of different allocation behaviors depend differently on ToM, with charity and reciprocity eliciting greater attention to individuals' unique states and motivations.

Electronic cigarettes ("e-cigs") have recently gained in popularity, but their health risks, including dependence potential are unclear. This study analyzed the adult database from the Wave 1 Population Assessment of Tobacco and Health (PATH) Study, a nationally representative survey of tobacco use in the United States, to assess the relative level of dependence among adult, exclusive everyday users of e-cigarettes and cigarettes. Of the total 32,320 observations from the Wave 1 PATH adult database, 3586 (5.9%, weighted) were eligible for our analysis population. Among those who met the eligibility criteria, 156 (4.6%) were exclusive e-cig users, and 3430 (95.4%) were exclusive cigarette smokers. Our results show that e-cig users reported a significantly longer time-to-first-use of the day after waking (measured in minutes) compared to cigarette smokers after adjusting for confounders (adjusted geometric mean [95% confidence limits (CL)]: 29.2 [24.4-34.9] vs. 20.0 [18.7, 21.5]). In addition, cigarette smokers were significantly more likely to consider themselves addicted (Adj. Odds Ratio [95% CL]: 6.9 [4.5-10.7]); have strong cravings (2.9 [1.9-4.2]); find it difficult in the past 12months to refrain from using their product in places where it was prohibited (6.4 [2.9-14.3]); and feel like they really needed to use their product (3.9 [2.4-6.4]). These results are consistent with previous studies, in finding that exclusive daily e-cigarette users are less dependent on their respective product than comparable cigarette smokers.

Introduction: The incidence of prostate cancer (PC) is known to vary within Appalachia, with Northern Appalachia and Southern Appalachia having higher and lower rates, respectively. However, the geographical disparity for aggressive PC has not been investigated. The objective of this study was to determine whether having more aggressive PC was associated with residing in an Appalachian/non-Appalachian county and rural/urban community. Methods: A cross-sectional study was conducted among men, aged &gt = 40 years, who had a primary, clinical PC diagnosis identified in the Pennsylvania Cancer Registry between 2004 and 2014. PC aggressiveness was defined as less aggressive (Gleason score 6 or 7 [3+4] and clinical/pathologic tumor stage T1-T2) and more aggressive (Gleason score &gt = 7 [4+3], clinical/pathologic tumor stage T3-T4, or distant metastasis) PC. Logistic regression analysis was used to examine the association between having aggressive PC (less vs more aggressive PC - dependent variable) and residing in a geographical region (Appalachian versus non-Appalachian county - independent variable), stratified by rural/urban, after adjusting for age, race, ethnicity, insurance status, marital status, serum PSA, positive lymph node status, and cancer treatment. Results: There were 94,264 PC cases, aged 40 to 105 years, included in the study. The majority of the PC cases were white (83.9%) followed by black race (10.7%). PC cases from urban Appalachian counties (35.42%) had the highest frequency of aggressive PC followed by rural non-Appalachian (34.18%), rural Appalachian (32.12%), and urban non-Appalachian counties (32.08%). In urban areas, Appalachian PC cases were more likely to be aggressive compared to non-Appalachian PC cases, after adjusting for confounders (odds ratio [O.R.] =1.16; 95% confidence interval [C.I.], 1.13-1.21). Conversely, in rural areas, Appalachian PC cases were less likely to be aggressive compared to non-Appalachian PC cases, after adjusting for confounders (O.R. =0.91; 95% C.I., 0.85-0.98). Conclusion: Differences in having more aggressive PC was observed for Appalachian populations by rural/urban status, with urban Appalachian PC cases more likely and rural Appalachian PC cases less likely to have more aggressive disease, compared to their non-Appalachian counterparts. Further investigation on the underlying mechanisms of aggressive PC in urban Appalachia in PA is warranted. Citation Format: Alicia C. McDonald, Emily Wasserman, Eugene J. Lengerich, Jay D. Raman, Nathaniel Geyer, Raymond Hohl, Ming Wang. Aggressive prostate cancer among men in Pennsylvania: Differences between Appalachian and non-Appalachian counties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4186.

OBJECTIVES/SPECIFIC AIMS: This study aims to determine if a bronchiolitis specific microbiome exists and how it evolves through disease course. Objective 1. Determine the microbiome profile of the airway in virus induced bronchiolitis-associated respiratory failure. Objective 2. Identify changes in the airway microbiome profile through the course of virus induced bronchiolitis associated respiratory failure, and the relationship between microbiome composition and clinical respiratory status. Objective 3. Determine the impact of rhinovirus infection on the lung and stool microbiome in a murine asthma model. METHODS/STUDY POPULATION: Objectives 1 &2: We are conducting a single-center prospective case-control study of patients admitted to the Komansky - Weill Cornell Pediatric Critical Care Unit. Infants less than two years of age with a diagnosis of bronchiolitis requiring intubation and mechanical ventilation are enrolled as subjects. Infants less than two years of age intubated and requiring mechanical ventilation without primary lung pathology are enrolled as controls. To evaluate our primary objective, tracheal aspirates will be collected from both subjects and controls on the day of intubation. We will perform 16s RNA sequencing on the tracheal aspirate samples and compare the resulting microbiomes. To evaluate secondary objective, we will collect tracheal aspirates of our study population on a daily basis and map the microbiome in parallel with objective measures of respiratory status including oxygen index and successful extubation. Both subjects and controls are being enrolled as a convenience sample. Objective 3: Mice, heterozygous for the sptlc2 gene (Spltc2 +/−) demonstrate reduced de-novo sphingolipids and increased airway hyperresponsiveness with methacholine challenge. Airway hyper-responsiveness is a cardinal feature of asthma. This airway hyperresponsiveness is exacerbated in the setting of rhinovirus (Figure 1). Using 16s sequencing, we will examine the lung microbiome of Sptlc2 +/− ad Sptlc2 +/+ at 1- and 7-days following rhinovirus infection. RESULTS/ANTICIPATED RESULTS: This clinical study is currently IRB approved and enrollment is ongoing. We have enrolled 12 subjects and 5 controls. Sample analysis will begin following the 2018-2019 respiratory season, with an anticipated cohort of 20 subjects and 20 controls. With regards to the murine studies, we have demonstrated that the lung microbiome of Sptlc2 +/− and Sptlc2 +/+ mice is similar at baseline (Figure 2) and remains similar following 1-day infection with rhinovirus. We do however, see a distinct change in the microbiome profile of the stool of Sptlc2 +/− mice following rhinovirus infection (Figure 3). Lung analysis at day 7 post infection is pending. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will lay the groundwork for detailing the functional role of the airway microbiome in bronchiolitis, with the objective of developing new modalities for disease treatment and prevention. In addition our murine studies allow us to view the microbiome in the context of sphingolipid deficiency, providing a potential mechanistic link to rhinovirus and ORMDL3 associated asthma.