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Background: Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH). Studies have generated inconsistent results regarding etiological factors for NCI in PLWH. Furthermore, a user-friendly and readily available predictive tool is desirable in clinical practice to screen PLWH for NCI. Objective: This study aimed to identify factors associated with NCI using a large and diverse sample of PLWH and build a nomogram based on demographic, clinical, and behavioral variables. Methods: We performed Bayesian network analysis using a supervised learning technique with the Markov Blanket (MB) algorithm. Logistic regression was also conducted to obtain the adjusted regression coefficients to construct the nomogram. Results: Among 1,307 participants, 21.6% were neurocognitively impaired. During the MB analysis, age provided the highest amount of mutual information (0.0333). Logistic regression also showed that old age (>50 vs. ≤50 years) had the strongest association (OR=2.77, 95% CI=1.99-3.85) with NCI. The highest possible points on the nomogram were 626, translated to a nomogram-predicted probability of NCI to be approximately 0.95. The receiver operating characteristic (ROC) curve's concordance index was 0.75, and the nomogram's calibration plot exhibited an excellent agreement between observed and predicted probabilities. Conclusion: The nomogram used variables that can be easily measured in clinical settings and, thus, easy to implement within a clinic or web-interface platform. The nomogram may help clinicians screen for patients with a high probability of having NCI and thus needing a comprehensive neurocognitive assessment for early diagnosis and appropriate management.

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12 years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92–2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91–1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.

Personal protective equipment used by healthcare workers to mitigate disease transmission risks while caring for patients with high-consequence infectious diseases can impair normal body cooling mechanisms and exacerbate physiological strain. Symptoms of heat strain (e.g., cognitive impairment, confusion, muscle cramping) are especially harmful in the high-risk environment of high-consequence infectious disease care. In this pilot study, the core body temperatures of healthcare workers were assessed using an ingestible, wireless-transmission thermometer while performing patient care tasks common to a high-level isolation unit setting in powered air purifying respirator (PAPR)-level. The objective was to determine the potential for occupational health hazard due to heat stress in an environmentally controlled unit. Maximum core temperatures of the six participants ranged from 37.4 °C (99.3 °F) to 39.9 °C (103.8

Background Heart failure (HF) is a multifaceted syndrome that requires self-management for adherence to treatment to control symptoms. Symptoms need to be monitored to prevent impending HF exacerbations. Few HF study authors have assessed efficacy of mobile health (mHealth) interventions particularly with virtual visits to evaluate outcomes such as symptoms and healthcare utilization. Objective The aim of this pilot study was to evaluate the potential effect of mHealth self-management interventions on symptom status and health-related quality of life and describe health care utilization in patients with HF. Methods This 3-month pilot study included 74 patients with HF and used a randomized 3-group repeated-measures design (enhanced usual care, mHealth, and mHealth plus [+] virtual visits). Surveys included the Heart Failure Symptom Survey, EuroQol, and a specialized phone application for patients to report weights and medications. Results The mHealth groups had an overall decrease in most symptom severity and frequency, particularly shortness of breath. Compared to enhanced usual care, both the mHealth+ and mHealth groups showed promise with medium effect sizes (range .55-.60) in relation to shortness of breath and a medium effect (.51) for lower extremity edema for the mHealth+ group. There was a trend toward improvement in health-related quality of life in both intervention groups at month 3. The mHealth+ group had fewer rehospitalizations. Conclusions In general, both mHealth groups fared better on symptoms and health care utilization. Small to medium effect sizes on selected symptom outcomes warrant this study to be conducted in a fully powered study. Virtual visits may assist in symptom recognition and self-management.

Cutaneous squamous cell carcinoma (SCC) causes approximately 1,000,000 cases and 9000 deaths each year in the United States. While individual tumor sequencing studies have discovered driver mutations in SCC, there has yet to be a review and subsequent analysis synthesizing current studies. To conduct a comprehensive synthesis and analysis of SCC sequencing studies with individual patient-level data, a comprehensive literature search was performed. Statistical analyses were performed to identify trends. Studies meeting inclusion criteria included a total of 279 patients (189 localized SCCs, 90 metastatic SCCs). Several mutations were correlated with demographic characteristics (TP53, MLL4, BRCA2, COL4A1). TP53, TERT, SPEN, MLL3, and NOTCH2 mutations were significantly more likely to be found in metastatic versus localized SCCs even after the Bonferroni correction for multiple comparisons. Silent mutations were found more in localized SCCs than metastatic SCCs, and nonsense mutations were found more in metastatic SCCs than localized SCCs (p = 0.0003 and p = 0.04, respectively). Additional mutations were identified that have not yet been explored in SCC including AHNAK2, LRP1B, TRIO, MDN1, COL4A2, SVIL, VPS13C, DST, DMD, and DYSF. Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.

Background A comprehensive battery of tests are used to inform return to play decisions following anterior cruciate ligament (ACL) reconstruction. Performance measures contribute to patient function, but it is not clear if achieving symmetrical performance on strength and hop tests is sufficient or if a patient also needs to meet minimum unilateral thresholds. Hypothesis/Purpose To determine the association of quadriceps strength and single-leg forward hop performance with patient-reported function, as measured by the IKDC Subjective Knee Form (IKDC), during late-stage ACL rehabilitation. A secondary purpose was to determine which clinical tests were the most difficult for participants to pass. Study Design Descriptive Laboratory Study Methods Forty-eight individuals with a history of ACL-R (32 female, 16 male; mean±SD age=18.0±2.7 y; height=172.4±7.6 cm; mass=69.6±11.4 kg; time since surgery=7.7±1.8 months; IKDC=86.8±10.6) completed the IKDC survey, quadriceps isometric strength, and single-leg forward hop performance. The relationship between IKDC scores and performance measures (LSI and involved limb) was determined using stepwise linear regression. Frequency counts were used to determine whether participants met clinical thresholds (IKDC ≥ 90%, quadriceps and single-leg forward hop LSI ≥ 90%, quadriceps peak torque ≥ 3.0 Nm/kg, and single-leg forward hop ≥ 80% height for females and ≥ 90% height for males). Results Quadriceps LSI and involved limb peak torque explained 39% of the variance in IKDC scores while measures of single-leg forward hop performance did not add to the predictive model. Nearly 90% of participants could not meet established clinical thresholds on all five tests and quadriceps strength (LSI and peak torque) was the most common unmet criteria (71% of participants). Conclusions During late-stage ACL rehabilitation deficits in quadriceps strength contribute more to patient function and are greater in magnitude compared to hop test performance. Level of evidence Cross-Sectional Study, Level 3, This study investigates the association of quadriceps strength and single-leg forward hop performance with patient-reported function, during late-stage ACL rehabilitation, as well as which tests are more difficult to pass.

Objective Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. Background Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). Methods The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. Results Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. Conclusions Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

Background: We used the Therapy Preference Scale, a 30-item questionnaire, to determine cancer treatment preferences of adults with cancer. Methods: We used Wilcoxon’s rank sum test and Fisher’s exact test to compare the preferences of younger (

Background: Several family-based efficacious pediatric weight management interventions (PWMIs) have been developed to reduce child weight status. These programs are typically based in larger cities...

ObjectiveThe role of aromatherapy in supportive symptom management for pediatric patients receiving palliative care has been underexplored. This pilot study aimed to measure the impact of aromatherapy using validated child-reported nausea, pain, and mood scales 5 minutes and 60 minutes after aromatherapy exposure.MethodsThe 3 intervention arms included use of a symptom-specific aromatherapy sachet scent involving deep breathing. The parallel default control arm (for those children with medical exclusion criteria to aromatherapy) included use of a visual imagery picture envelope and deep breathing. Symptom burden was sequentially assessed at 5 and 60 minutes using the Baxter Retching Faces scale for nausea, the Wong-Baker FACES scale for pain, and the Children's Anxiety and Pain Scale (CAPS) for anxious mood. Ninety children or adolescents (mean age 9.4 years) at a free-standing children's hospital in the United States were included in each arm (total n = 180).ResultsAt 5 minutes, there was a mean improvement of 3/10 (standard deviation [SD] 2.21) on the nausea scale; 2.6/10 (SD 1.83) on the pain scale; and 1.6/5 (SD 0.93) on the mood scale for the aromatherapy cohort (p< 0.0001). Symptom burden remained improved at 60 minutes post-intervention (Significance of resultsAromatherapy represents an implementable supportive care intervention for pediatric patients receiving palliative care consults for symptom burden. The high number of children disqualified from the aromatherapy arm because of pulmonary or allergy indications warrants further attention to outcomes for additional breathing-based integrative modalities.

BACKGROUND: Respiratory therapists (RTs) are care providers in highly stressful work environments with limited time and resources for self-care. Mindfulness-based interventions teach non-reactive awareness to the present situation or the ability to respond versus react in the moment, to shift away from a physical and emotional stress response. METHODS: Mindfulness-based group learning was offered during 2 regularly scheduled RT staff meetings for ∼30 min each session. Each meeting began and concluded with a distress assessment and with counting and recording respirations for 30 s. RESULTS: This quality-improvement project revealed mindfulness-based interventions to be feasible and acceptable. Mindfulness intervention reduced RT team members9 physical and emotional stress related symptoms (as measured by a 1-point median decrease in the self-administered distress assessment, with P = .001 in session 1) and increased sense of calm (as measured by participant breathing rate decrease by mean of two-points P = .001 in session 1 and session 2). CONCLUSIONS: Mindfulness-based interventions were noted to be feasible and acceptable additions to RT staff meetings. These interventions have the potential to introduce breathing practices and mini mindfulness techniques.

Our goal is to address the need for driver-state detection using wearable and in-vehicle sensor measurements of driver physiology and health. To address this goal, we deployed in-vehicle systems, wearable sensors, and procedures capable of quantifying real-world driving behavior and performance in at-risk drivers with insulin-dependent type 1 diabetes mellitus (DM). We applied these methodologies over 4 weeks of continuous observation to quantify differences in real-world driver behavior profiles associated with physiologic changes in drivers with DM (N=19) and without DM (N=14). Results showed that DM driver behavior changed as a function of glycemic state, particularly hypoglycemia. DM drivers often drive during at-risk physiologic states, possibly due to unawareness of impairment, which in turn may relate to blunted physiologic responses (measurable heart rate) to hypoglycemia after repeated episodes of hypoglycemia. We found that this DM driver cohort has an elevated risk of crashes and citations, which our results suggest is linked to the DM driver's own momentary physiology. Overall, our findings demonstrate a clear link between at-risk driver physiology and real-world driving. By discovering key relationships between naturalistic driving and parameters of contemporaneous physiologic changes, like glucose control, this study directly advances the goal of driver-state detection through wearable physiologic sensors as well as efforts to develop "gold standard" metrics of driver safety and an individualized approach to driver health and wellness.

Implementation of pediatric palliative care as a primary practice relevant for all pediatricians and pediatric subspecialists requires a grounding, shared knowledge. This study reports on the innovative application of a monthly Palliative Care E-Journal Club (Pal Care Club) to foster shared palliative care knowledge hospital wide.To explore the impact of a monthly electronic journal club to increase the number of palliative care-relevant articles read and discussed and to enhance provider comfort with the integration and introduction of palliative care.A single cohort, predesign-post-design was utilized to explore the impact of a monthly palliative care electronic journal club.Preintervention barriers to reading pediatric palliative care literature were primarily access and time. The mean of paired differences (post-pre) for the number of full-text articles read per month was 2.56 (SD = 1.25). The journal club intervention increased participant personal comfort with integrating palliative care principles at the bedside (p 0.0001) and introducing pediatric palliative care to patients and families (p 0.0001).An electronic journal club is a feasible and acceptable means of increasing number of palliative care articles read and discussed across an institution as well as enhancing pediatric palliative care knowledge across subspecialist and general pediatric services.

Introduction: Rigor and reproducibility are two important cornerstones of medical and scientific advancement. Clinical and translational research (CTR) contains four phases (T1–T4), involving the translation of basic research to humans, then to clinical settings, practice, and the population, with the ultimate goal of improving public health. Here we provide a framework for rigorous and reproducible CTR. Methods: In this paper we define CTR, provide general and phase-specific recommendations for improving quality and reproducibility of CTR with emphases on study design, data collection and management, analyses and reporting. We present and discuss aspects of rigor and reproducibility following published examples of CTR from the literature, including one example that shows the development path of different treatments that address anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). Results: It is particularly important to consider robust and unbiased experimental design and methodology for analysis and interpretation for clinical translation studies to ensure reproducibility before taking the next translational step. There are both commonality and differences along the clinical translation research phases in terms of research focuses and considerations regarding study design, implementation, and data analysis approaches. Conclusions: Sound scientific practices, starting with rigorous study design, transparency, and team efforts can greatly enhance CTR. Investigators from multidisciplinary teams should work along the spectrum of CTR phases, and identify optimal practices for study design, data collection, data analysis, and results reporting to allow timely advances in the relevant field of research.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy demonstrating aberrant and progressive expression of mucins. The contribution of individual mucins has been extensively investigated in PDAC; however, comprehensive mucin profiling including splice variants in PDAC tumors has not been reported. Experimental Design: Using publicly available RNA sequencing (RNA-seq) datasets, we assess the expression of mucin family members and their splice variants (SV) in PDAC tumor samples for the first time. Mucin SVs that are correlated with PDAC patient survival are validated in a cohort of patient tumor samples. Further, we use computational methods to derive novel pancreatic tumor subtypes using mucin expression signatures and their associated activated pathways. Results: Principal component analysis identified four novel mucin-based PDAC subtypes. Pathway analysis implicated specific biological signatures for each subtype, labeled (i) immune activated, (ii) progressive, (iii) pancreatitis-initiated, and (iv) anti-inflammatory/PanIN-initiated. Assessing mucin SVs, significantly longer survival is observed with higher expression of 4 MUC1 and 1 MUC13 SVs, whereas patients expressing 2 MUC4 and 1 MUC16 SVs had shorter survival. Using a whole-transcriptome correlation, a three-gene panel, including ESRP2, PTK6, and MAGEH1, is designated to assess PDAC tumor sample cellularity by PCR. One MUC4 SV and one MUC13 SV are quantified in a separate PDAC patient cohort, and their effects on survival are experimentally validated. Conclusions: Altogether, we demonstrate the unique expression pattern of mucins, four mucin-based PDAC subtypes, and the contribution of MUC1, MUC4, and MUC16 SVs in PDAC patient survival.

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium’s (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64–0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56–0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

We incorporated questions related to safety, effectiveness and other characteristics of systemic cancer treatment into a self-report questionnaire – the Therapy Preference Scale – that captures patients´ preferences. The authors asked 20 experts to assess content validity and an additional 20 experts, patients and community members to examine face validity and guide revisions. Key revisions included shortening the length, clarifying constructs and providing details to explain the context and trade-offs necessary to balance the risks and benefits of cancer treatment. The content validity index for the final questionnaire was 1.0, indicating that all questions were relevant. Reviewers expressed that the questionnaire would serve an important purpose. Experts, patients and community members guided revisions of the questionnaire and documented its value.

Purpose Prefabricated arrays with a limited number of electrodes offer an opportunity to hasten the diagnosis of seizures; however, their accuracy to detect seizures is unknown. We examined the utility of two limited-montage EEG setups for the detection of nonconvulsive seizures. Methods Thirty previously interpreted EEG segments with nonconvulsive seizures from 30 patients and 60 segments with background slowing or normal EEG from 60 patients were rendered in a bipolar "double banana" montage, a double distance "neonatal" montage, and a circumferential "hatband" montage. Experts reviewed 60 to 180 seconds long segments to determine whether seizures were present and if the EEG data provided were sufficient to make a decision on escalation of clinical care by ordering an additional EEG or prescribing anticonvulsants. The periodic patterns on the ictal-interictal continuum were specifically excluded for this analysis to keep the focus on definite electrographic seizures. Results The sensitivities for seizure of the neonatal and hatband montages were 0.96 and 0.84, respectively, when compared with full montage EEG, whereas the specificities were 0.94 and 0.98, respectively. Appropriate escalation of care was suggested for 96% and 92% of occurrences of seizure patterns in neonatal and hatband montages, respectively. When compared with clinical EEG, the sensitivities of the neonatal and hatband montages for seizure diagnosis were 0.85 and 0.69, respectively. Conclusions Nonconvulsive seizures were detected with high accuracy using the limited electrode array configuration in the neonatal and hatband montages. The sensitivity of the neonatal montage EEG in detecting seizures was superior to that of a hatband montage. These findings suggest that in some patients with nonconvulsive seizures, limited-montage EEG may allow to differentiate ictal and slow patterns.

A data driven approach to guide the global, regional and local pandemic recovery planning is key to the safety, efficacy and sustainability of all pandemic recovery efforts. The Pandemic Recovery Acceleration Model (PRAM) analytic tool was developed and implemented state wide in Nebraska to allow health officials, public officials, industry leaders and community leaders to capture a real time snapshot of how the COVID-19 pandemic is affecting their local community, a region or the state and use this novel lens to aid in making key mitigation and recovery decisions. This is done by using six commonly available metrics that are monitored daily across the state describing the pandemic impact: number of new cases, percent positive tests, deaths, occupied hospital beds, occupied intensive care beds and utilized ventilators, all directly related to confirmed COVID-19 patients. Nebraska is separated into six Health Care Coalitions based on geography, public health and medical care systems. The PRAM aggregates the data for each of these geographic regions based on disease prevalence acceleration and health care resource utilization acceleration, producing real time analysis of the acceleration of change for each metric individually and also combined into a single weighted index, the PRAM Recovery Index. These indices are then shared daily with the state leadership, coalition leaders and public health directors and also tracked over time, aiding in real time regional and statewide decisions of resource allocation and the extent of use of comprehensive non-pharmacologic interventions.

Author(s): May, Pamela E; Heithoff, Abigail J; Wichman, Christopher S; Phatak, Vaishali S; Moore, David J; Heaton, Robert K; Fox, Howard S | Abstract: BackgroundSingle summary scores, such as the Global Deficit Score, are often used to classify overall performance on neuropsychological batteries. The factor structure of test scores that underlie Global Deficit Score in studies of people living with HIV (PLWH) was assessed to determine whether individual test scores loaded onto a unitary factor to summarize performance.SettingSecondary data analysis on baseline data of PLWH from National NeuroAIDS Tissue Consortium and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study.MethodPrimary analyses included testing model structure and fit of neuropsychological test scores with confirmatory and exploratory factor analyses. Secondary analyses involved receiver operating characteristic curves, and associations with psychosocial and medical variables.ResultsParticipants with confounds were excluded, leading to 798 (National NeuroAIDS Tissue Consortium) and 1222 (CHARTER) cases. When confirmatory factor analysis models were structured to be consistent with theoretically-based cognitive domains, models did not fit adequately. Per exploratory factor analyses, tests assessing speeded information processing, working memory, and executive functions loaded onto a single factor and explained the most variance in both cohorts. This factor tended to be associated with age, estimated premorbid ability, and aspects of substance use history. Its relation to age, in context of demographically corrected neuropsychological scores, suggested accelerated aging.ConclusionResults indicate that individual neuropsychological tests did not load exactly onto expected domains, suggesting another framework for future analyses of cognitive domains. The possibility of a new index, and its use to assess cognitive impairment in PLWH, is suggested for further diagnostic and prognostic purposes.

Background and Objectives:Cardiac surgical interventions for children with trisomy 18 and trisomy 13 remain controversial, despite growing evidence that definitive cardiac repair prolongs survival. Understanding quality of life for survivors and their families therefore becomes crucial. Study objective was to generate a descriptive summary of parental perspectives on quality of life, family impact, functional status, and hopes for children with trisomy 18 and trisomy 13 who have undergone heart surgery.Methods:A concurrent mixed method approach utilising PedsQL™ 4.0 Generic Core Parent Report for Toddlers or the PedsQL™ Infant Scale, PedsQL™ 2.0 Family Impact Module, Functional Status Scale, quality of life visual analogue scale, and narrative responses for 10 children whose families travelled out of state to access cardiac surgery denied to them in their home state due to genetic diagnoses.Results:Parents rated their child’s quality of life as 80/100, and their own quality of life as 78/100 using validated scales. Functional status was rated 11 by parents and 11.6 by providers (correlation 0.89). On quality of life visual analogue scale, all parents rated their child’s quality of life as “high” with mean response 92.7/100. Parental hopes were informed by realistic perspective on prognosis while striving to ensure their children had access to reaching their full potential. Qualitative analysis revealed a profound sense of the child’s relationality and valued life meaning.Conclusion:Understanding parental motivations and perceptions on the child’s quality of life has potential to inform care teams in considering cardiac interventions for children with trisomy 18 and trisomy 13.

Background Aortic elasticity creates a cushion that protects the heart from pressure injury, and a recoil that helps perfuse the coronary arteries. TEVAR has become first-line therapy for many aortic pathologies including trauma, but stent-grafts stiffen the aorta and likely increase LV afterload. Objective Test the hypothesis that trauma TEVAR is associated with LV mass increase and adverse off-target aortic remodeling. Methods Computed Tomography Angiography (CTA) scans of 20 trauma TEVAR patients (17 M/3 F) at baseline [age 34.9 ± 18.5 (11.4-71.5) years] and 5.1 ± 3.1 (1.1-12.3) years after repair were used to measure changes in LV mass, LV mass index, and diameters and lengths of the ascending thoracic aorta (ATA). Measurements were compared with similarly-aged control patients without aortic repair (21 M/21 F) evaluated at similar follow-ups. Results LV mass and LV mass index of TEVAR patients increased from 138.5 ± 39.6 g and 72.35 ± 15.17 g/m to 173.5 ± 50.1 g and 85.48 ± 18.34 g/m at the rate of 10.03 ± 12.79 g/yr and 6.25 ± 10.28 g/m/yr, whereas in control patients LV characteristics did not change. ATA diameters of TEVAR patients increased at a rate of 0.60 ± 0.80 mm/yr, which was 2.4-fold faster than in controls. ATA length in both TEVAR and control patients increased at 0.58 mm/yr. Half of TEVAR patients had hypertension at follow-up compared to only 5% at baseline. Conclusions TEVAR is associated with LV mass increase, development of hypertension, and accelerated expansile remodeling of the ascending aorta. Although younger trauma patients may adapt to these effects, these changes may be even more important in older patients with other aortic pathologies and diminished baseline cardiac function.

School engagement protects against negative mental health outcomes; however, few studies examined the relationship between school engagement and attention-deficit hyperactivity disorder (ADHD) using an ecological framework. The aims were to examine: (1) whether school engagement has an independent protective association against the risk of ADHD in children, and (2) whether environmental factors have an association with ADHD either directly or indirectly via their association with school engagement. This cross-sectional study used data from the 2011–2012 National Survey of Children’s Health, which collected information about children’s mental health, family life, school, and community. The sample contained 65,680 children aged 6–17 years. Structural equation modeling was used to estimate the direct association of school engagement and ADHD and indirect associations of latent environmental variables (e.g., family socioeconomic status (SES), adverse childhood experiences (ACEs), environmental safety, and neighborhood amenities) and ADHD. School engagement had a direct and inverse relationship with ADHD (β = − 0.35, p

// Bradley R. Hall 1, 2 , Andrew Cannon 2 , Pranita Atri 2 , Christopher S. Wichman 3 , Lynette M. Smith 3 , Apar K. Ganti 4, 5 , Chandrakanth Are 1 , Aaron R. Sasson 6 , Sushil Kumar 2 and Surinder K. Batra 2, 7 1 Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE, USA 2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA 3 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA 4 Department of Internal Medicine, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA 5 Department of Internal Medicine, Division of Hematology and Oncology, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA 6 Department of Surgery, Division of Surgical Oncology, Stony Brook School of Medicine, Stony Brooke, NY, USA 7 Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA Correspondence to: Surinder K. Batra, email: sbatra@unmc.edu Keywords: pancreatic ductal adenocarcinoma; meta-analysis; metastasis; chemotherapy; survival Received: December 09, 2017 Accepted: March 09, 2018 Published: April 10, 2018 ABSTRACT Background: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. Materials and methods: All Phase 2–4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. Results: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). Conclusions: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. Funding: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).

Background: Little is known about the composition, availability, integration, communication, perceived barriers, and work load of pediatric palliative care (PPC) providers serving children and adolescents with cancer. Objective: To summarize the structure and services of programs to better understand successes and gaps in implementing palliative care as a standard of care. Methods: Cross-sectional online survey about the palliative care domains determined by the Psychosocial Care of Children with Cancer and Their Families Workgroup. Subjects: A total of 142 surveys were completed with representation from 18 countries and 39 states. Results: Three-fourths of sites reported having a PPC program available for the pediatric cancer population at their center. Over one-fourth (28%) have been in existence less than five years. Fewer than half of sites (44%) offered 24/7 access to palliative care consultations. Neither hospital-based nor local community hospice services were available for pediatric patients at 24% of responding sites. A specific inpatient PPC unit was available at 8% of sites. Criteria for automatic palliative referrals (“trigger” diagnoses) were reported by 44% respondents. The presence of such “triggers” increased the likelihood of palliative principle introduction 3.41 times (p

This pilot study tackles the overarching need for driver-state detection through real-world measurements of driver behavior and physiology in at-risk drivers with type 1 diabetes mellitus (DM). 35 drivers (19 DM, 14 comparison) participated. Real-time glucose levels were measured over four weeks with continuous glucose monitor (CGM) wearable sensors. Contemporaneous real-world driving performance and behavior were measured with in-vehicle video and electronic sensor instrumentation packages. Results showed clear links between at-risk glucose levels (particularly hypoglycemia) and changes in driver performance and behavior. DM participants often drove during at-risk glucose levels (low and high) and showed cognitive impairments in key domains for driving, which are likely linked to frequent hypoglycemia. The finding of increased driving risk in DM participants was mirrored in state records of crashes and traffic citations. Combining sensor data and phenotypes of driver behavior can inform patients, caregivers, safety interventions, policy, and design of supportive in-vehicle technology that is responsive to driver state.

Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma.

Background: Rural pediatricians and adult-trained hospice teams report feeling ill-prepared to care for children at end of life, resulting in geographies in which children are not able to access home-based services. Objectives: To develop a pediatric palliative care curriculum for inpatient nurses and adult-trained hospice teams caring for children in a rural region. Methods: Curriculum design and delivery was informed by local culture through an interdisciplinary, iterative development approach with confidence, intention, and support measured pre-, post-, and 4 months after delivery. A needs assessment was completed by pediatric nurses caring for children receiving palliative or end-of-life care to inform curricular content (phase 1). A curriculum was designed by an interdisciplinary pediatric palliative care team and piloted with nursing cohorts annually through educational conferences with monthly discussion series for 3 consecutive years (phase 2). Curricular content was then provided for 31 rural hospice team members (phase 3). Results: Self-reported confidence in caring for children increased by 1.1/10 points for adult-trained hospice team members. Mean score for intention to care for children increased by 5.2 points (sustained 5.1 points above baseline at 4 months). Perception of support in caring for children increased by 5 points (mean sustained 5.4 points above baseline at 4 months). Family needs, care goals, and symptom management were prioritized learning topics. Rural hospices previously unwilling to accept children enrolled pediatric patients in the 4 months following the conference. Conclusion: Grassroots curricular initiatives and ongoing educational mentorship can grow pediatric palliative and hospice services in rural regions.

7021 Background: GA can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with OS in AML. We previously reported a reduction in early mortality in a pre-planned interim analysis of a phase II trial with the use of GA and genetic profiling to personalize therapy selection (NCT03226418) (Blood 2019; 134(s1):120). Here, we present the results of a propensity score matched analysis demonstrating an improvement in OS over a historical control. Methods: Patients ≥60 years with a new diagnosis of AML underwent GA. Patients were considered fit for intensive chemotherapy if they had robust physical function [normal activities of daily living (ADL) and instrumental ADL, and short physical performance battery score of ≥10 out of 12], normal cognitive function (Montreal Cognitive Assessment score of ≥26 out of 30), and hematopoietic cell transplantation comorbidity index (HCT CI) of 0-2 (except for treatment related AML, where a score of 0-2 in addition to the prior history of malignancy was acceptable). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 ELN criteria. Fit patients with good or intermediate-risk AML received intensive chemotherapy. Patients with high-risk AML received low-intensity chemotherapy, or CPX 351 if they were fit and met the FDA-approved indications. Pragmatic aspects of the trial included broad eligibility criteria (e.g. patients on treatment for other malignancy were enrolled) and co-management of patients with community oncologists. Mortality was compared with a historical control treated during the years 2004-2016 (after approval of HMA) and matched on gender, age, Karnofsky Performance Status (KPS), HCT CI and ELN risk category. Results: Treatment group (n = 27) vs. historical controls (n = 32) were matched in terms of age (median age, 70 vs. 68.5 years), ELN risk category (adverse risk 59% vs. 53%), HCT CI (median score of 2), KPS (median 80 vs. 85), and gender (male 44% vs. 50%). In the treatment group, 3 patients received intensive chemotherapy: CPX 351 (n = 2) or 7+3+ gemtuzumab (n = 1). Other patients received HMA alone (n = 16), decitabine and midostaurin (n = 3), or azacitidine and venetoclax after the approval of venetoclax (n = 5). Treatment in the historical control included intensive chemotherapy (n = 20) such as 7+3, or mostly HMA based low intensity chemotherapy (n = 12). OS was significantly higher in the treatment group over historical control with 1-year OS of 66% (95% CI 60-87%) vs. 16% (95% CI 7-35%). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both GA for patient profiling and genetic profiling of leukemia cells. Our results appear promising with superior OS (an absolute difference of 50% in 1-year OS) compared to a matched historical control. Clinical trial information: NCT03226418.

Statement of problem To our knowledge, no data are available on the actual lighting that is used for visual shade matching in private dental offices. Purpose The purpose of this study was to determine the shade matching practices and interest in continuing education in dental practices and to determine the quantity and quality of the ambient lighting used during visual shade matching in a sample cohort of dentists in private practices. Material and methods Thirty-two private practices were enrolled, and each completed a 1-page survey on the clinic’s shade matching practices. A spectrophotometer was used to measure the ambient lighting in each practice, collecting data on color temperature (Kelvin), color rendering index (CRI), and light intensity (foot candles/fc). A 2-sided nonparametric sign test was used to compare the true median color temperature with the standard (5500°K). A 1-sided t test was used to compare the CRI with the standard (CRI >90) (α=.05 for all statistical analyses). Results All dental practitioners surveyed used mainly visual shade matching in their practices. Of those, 87.5% showed interest in attending continuing education on this topic, with 56.3% preferring a clinical demonstration course. The mean color temperature was 4152.9°K and was significantly different from the standard 5500°K ( P t test indicated that the mean CRI was less than 90 ( P =1). The 95% confidence interval for the intensity was 80.7 to 111.6 fc. Conclusions The ambient light in the majority of the 32 dental private practices measured was not ideal for visual shade matching.

The primary aim of this study was to determine the characteristics that current chairpersons in restorative dentistry, general dentistry, prosthodontics, and operative dentistry departments in U.S. dental schools feel are most relevant in contributing to their success. The secondary aim was to determine these individuals' rankings of the importance of a listed set of characteristics for them to be successful in their position. All 82 current chairs of the specified departments were invited to respond to an electronic survey. The survey first asked respondents to list the five most essential characteristics to serve as chair of a department and to rank those characteristics based on importance. Participants were next given a list of ten characteristics in the categories of management and leadership and, without being aware of the category of each individual item, asked to rank them in terms of importance for their success. A total of 39 chairpersons completed the survey (47.6% response rate; 83.3% male and 16.2% female). In section one, the respondents reported that leadership, vision, work ethic, integrity, communication, and organization were the most essential characteristics for their success. In section two, the respondents ranked the leadership characteristics as statistically more important than the management characteristics (p

Immunization rates among health care personnel (HCP) have remained low despite advances in vaccine development with reported rates ranging from 27% to 72% for commonly recommended vaccines. Within the United States, HCP are placing patients, families, and themselves at considerable risk for vaccine-preventable diseases. A significant source of infection, HCP are carriers of infectious agents and often unknowingly transmit these contagious diseases while experiencing minimal or no symptoms. This study examined the current immunization rates of HCP for influenza, tetanus, diphtheria, and pertussis (Tdap), and hepatitis B in Nebraska, as well as identified motivators and barriers to vaccination. Nebraska HCP surveyed included physicians, physician assistants, nurse practitioners, registered nurses, licensed practical nurses, medical assistants, nursing assistants, and clerical or administrative staff of nonrestricted ethnic backgrounds age 19 years and older. Nebraska HCP immunization rates were statistically above the national rates. Motivators and barriers were also identified for each vaccine.

Purpose This study investigates the clinical and cost effectiveness of switching from traditional vagus nerve stimulation (VNS) to responsive VNS (rVNS), which has an additional ictal tachycardia detection and stimulation (AutoStim) mode. Methods Retrospective chart review was used to collect data from patients with medically refractory epilepsy who underwent generator replacements. Patients with confounding factors such as medication changes were excluded. Vagus nerve stimulation parameters, seizure frequency, and healthcare costs were collected for the 1-year period following generator replacement with the rVNS device. Results Documented seizure frequency was available for twenty-five patients. After implant with rVNS, 28% of patients had an additional ≥ 50% seizure reduction. There was a significant decrease in the average monthly seizure count (p = 0.039). In patients who were not already free of disabling seizures (n = 17), 41.2% had ≥ 50% additional seizure reduction. There was no difference in healthcare costs during the 1-year follow-up after the rVNS implant compared with one year prior. Conclusions Ictal tachycardia detection and stimulation provided a significant clinical benefit in patients who were not free of disabling seizures with treatment from traditional VNS. There was no additional increase in healthcare costs during the first year after device replacement.

e24186 Background: Patients’ (pts) preferences, crucial in selecting an appropriate treatment (tx), are understudied in cancer pts. We developed a novel self-reported questionnaire “Therapy Preference Scale” (TPS) (J Geriatr Oncol. 2019:677-679, J Clin Oncol 2019 37: e23179-e23179). Our single-center prospective observational study utilized TPS to gain in-depth understanding of pts’ preferences of various aspects of cancer tx. Methods: Eligible pts were adults aged ≥19 y with a diagnosis of cancer. Pts were asked to complete TPS; this 30-item scale captures pts’ rating of the importance of safety, efficacy and other characteristics of cancer tx (on a scale of 0-10), and importance of one over the other aspects of tx (using a 4-item Likert scale). Demographics, cancer-specific and therapy-related data were collected. Descriptive statistics were used for analysis. Results: Total 100 pts were enrolled- 52% were receiving cancer tx; 40% had completed tx; 8% were newly diagnosed and had not yet started tx. Pts were willing to accept short term SE for increased life expectancy but valued maintenance of cognition, functional ability and QoL. 70% valued maintaining cognition, functional ability and quality of life (QoL) than increased life expectancy; 75% would accept cancer tx if it improved QoL but 88% would reject a harsh tx for improved life expectancy of ≤6 months. Conclusions: Avoiding long term side effects (SE), life threatening infections, tx burden and financial toxicity were most important to pts. Harsh tx with ≤6 months improvement of life was unacceptable. These findings will help physicians understand pt preferences and guide selection of tx that will meet pts’ goals of care, and may also have implications for insurance policies and drug approval. [Table: see text]

Background: Most rural adults do not meet current guidelines for physical activity (PA). A 12-week feasibility study tested the effectiveness of using the 5A’s model for PA counseling on rural adults’ PA behaviors. Methods: Inactive rural adults recruited from a primary care clinic were randomized to an intervention (n = 30) or control (n = 29) group. All subjects wore a Fitbit to track steps and active minutes. The intervention group completed action plans to improve self-regulatory PA strategies and received weekly motivational text messages to improve PA behaviors. Theory of planned behavior constructs and self-regulatory strategies of planning, goal setting, and tracking (steps and active minutes) were measured with both groups. The control group received the Fitbit only. Results: All individuals became more physically active; however, no significant differences between groups in active minutes or steps were found. All subjects, regardless of group, increased steps (P > .05). There were no statistically significant differences between groups on any of the theoretical variables. Conclusions: It is vitally important to continue to find ways to make PA a priority to improve the overall health and well-being of rural adults. Future research warrants adjusting the intervention dose and strategies to increase PA that can be maintained long term.

The national nursing shortage translates into a gap in home nursing care available to children with complex, chronic medical conditions and their family caregivers receiving palliative care consultations. A total of 38 home health nursing surveys were completed by families receiving pediatric palliative care consultation services at a freestanding children's hospital in the Midwest. The gap in the average number of nursing hours allotted versus received was 40 h/wk per family, primarily during evening hours. Parents missed an average of 23 hours of employment per week to provide hands-on nursing care at home, ranking stress regarding personal employment due to nursing shortage at 6.2/10. Families invested an average of 10 h/mo searching for additional nursing coverage and often resorted to utilizing more than 6 different home nurse coverage personnel per month. Families reported multiple delays to hospital discharges (mean, 15 days per delay) due to inability to find home nursing coverage. Respiratory technology and lack of Medicaid coverage (P < .02) correlated with the gap in home nursing access. This study examines how the pediatric home nursing shortage translates into a lived experience for families with children with complex medical conditions receiving palliative care.

Human Papilloma Virus (HPV) is the most common sexually transmitted disease with over 14 million infections in 2008. Certain HPV types have been identified in up to 70% of cases of cervical and anal cancers. Despite being safe and effective, HPV vaccination rates remain low. Vaccination and demographic data was collected pre-and post-intervention. Among 13 thru 17-year-old cohort females were significantly more likely to be fully vaccinated. Assessment also found that patients insured by Medicaid were significantly more likely to be fully vaccinated than patients insured privately. Post-intervention vaccination rate is similar to baseline rates. There was non-significant improvement in HPV vaccination coverage after intervention. Male and privately insured patients of Creighton's Pediatric Clinic have lower HPV vaccination coverage than their counterparts. More direct efforts are needed in vaccination process and policy in the clinic to improve immunization against HPV among children and adolescents.

One goal of pediatric palliative care is to maintain quality of life for children and their families. Quality-of-life investigations may be enhanced by considering clinically important metrics in addition to statistical significance.The purpose of this study was to longitudinally evaluate the effect of time on quality of life and family impact for pediatric palliative care patients across all diagnoses and ages.This prospective quality-of-life study included administration of a 23-item PedsQL™ Measurement Model to evaluate for physical, emotional, social, and cognitive dimensions of the child's quality of life and a 36-item PedsQL Family Impact Module to assess for the familial impact at time of initial palliative care consultation, Month 6, and Month 12.All pediatric patients who received a palliative care consultation in our Midwestern free-standing children's hospital over a five-year period were included in the longitudinal study (n = 87).Repeated measures ANOVA was used to investigate how proxy-reported quality of life and family impact changed with time with attentiveness to also follow trends in minimal clinically important difference (MCID) metrics.The emotional domain showed a statistically significant positive trend over the first six months of palliative care involvement (p = 0.049), while the physical domain (p = 0.028) and daily activity (p = 0.039) showed a positive improvement for the full year. In using a standard of MCID, the physical, emotional, and cognitive domains improved in the quality-of-life scale and the communication, worry, and daily activity domains improved in the family impact scale over 12 months.In considering quality-of-life analyses for pediatric palliative care programmatic improvements, providers may consider analyzing not only for statistical significance in collective data sets but also for clinically important difference over time.

Background: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). Methods: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. Results: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. Conclusion: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.