Community-engaged Systems for Population Health Improvement: A Novel Approach to Improve Diabetes Outcomes in Rural Communities.

BACKGROUND: Approaches to prevent and manage diabetes at a community population level are hindered because current strategies are not aligned with the structure and function of a community system. We describe a community-driven process based on local data and rapid prototyping as an alternative approach to create diabetes prevention and care management solutions appropriate for each community. We report on the process and provide baseline data for a 3-year case study initiative to improve diabetes outcomes in two rural Nebraska communities. METHODS: We developed an iterative design process based on the assumption that decentralized decision-making using local data feedback and monitoring will lead to the innovation of local sustainable solutions. Coalitions act as community innovation hubs and meet monthly to work through a facilitated design process. Six core diabetes measures will be tracked over the course of the project using the electronic health record from community clinics as a proxy for the entire community. RESULTS: Baseline data indicate two-thirds of the population in both communities are at risk for prediabetes based on age and body mass index. However, only a fraction (35% and 12%) of those at risk have been screened. This information led both coalitions to focus on improving screening rates in their communities. DISCUSSION: In order to move a complex system towards an optimal state (e.g., improved diabetes outcomes), stakeholders must have access to continuous feedback of accurate, pertinent information in order to make informed decisions. Conventional approaches of implementing evidence-based interventions do not facilitate this process.

Inequality in Children's Physical Activity Across Time-Segmented Youth Sport Practice.

Purpose: Youth sport (YS) is a community system for promoting children's physical activity (PA). Studies have examined mean PA during YS practices, but few have examined inequalities in the distribution of PA among children during practice time. This study examined PA inequality in time-segmented YS practices and differences in inequality by time segment characteristics. Methods: Children's PA and YS practices were examined using accelerometer and video observation data from a sample of YS teams (n = 36 teams, n = 101 practices) for third- through sixth-grade children (n = 392), approximately eight to 12 years old, in two rural U.S. communities. Practices were time-segmented into smaller units (episodes; n = 991). Episodes were assigned codes for purpose (e.g. warm-up), member arrangement (e.g. whole group), and setting demand (i.e. fosters participation, creates exclusion). Group accelerometer data were paired with episodes, and the Gini coefficient quantified inequality in activity counts and minutes of moderate-to-vigorous PA (MVPA). Beta generalized estimating equations examined the influence of episode structure on PA inequality. Results: Warm-up (Gini = 0.22), fitness (Gini = 0.24), and sport skill (Gini = 0.24) episodes had significantly lower inequality (p < .05) in activity counts than other purpose types. Management (Gini = 0.32) and strategy (Gini = 0.40) episodes had significantly greater inequality (p < .05) in MVPA minutes than other purpose types. Episodes fostering participation (Gini = 0.32) had significantly lower activity count inequality (p < .05) than episodes creating exclusion (Gini = 0.35). Conclusion: PA inequality among children during YS varied by practice structure. Metrics such as the Gini coefficient can illuminate inequalities in PA and may be useful for guiding efforts to improve population PA in children. Trial Registration: This study is registered at www.clinicaltrials.gov (Identifier: NCT03380143).

Reliability of an Instrumented Pressure Walkway for Measuring Walking and Running Characteristics in Young, Athletic Individuals.

Background: Spatiotemporal parameters of gait are useful for identifying pathological gait patterns and presence of impairments. Reliability of the pressure-sensitive ZenoTM Walkway has not been established in young, active individuals without impairments, and no studies to this point have included running. Purpose: The purposes of this study were to 1) determine if up to two additional trials of walking and running on the ZenoTM Walkway are needed to produce consistent measurements of spatiotemporal variables, and 2) establish test-retest reliability and minimal detectable change (MDC) values for common spatiotemporal variables measured during walking and running. Study Design: Cross-Sectional Laboratory Study. Methods: Individuals (n=38) in this cross-sectional study walked and ran at self-selected comfortable speed on a pressure-sensitive ZenoTM Walkway. Twenty-one participants returned for follow-up testing between one and 14 days later. Intraclass correlation coefficients (ICCs) were used to assess reliability of spatiotemporal variable means using three, four, or five passes over the ZenoTM Walkway and to assess test-retest reliability of spatiotemporal variables across sessions. Results: All variables showed excellent reliability (ICC > 0.995) for walking and running when measured using three, four, or five passes. Additionally, all variables demonstrated moderate to excellent test-retest reliability during walking (ICC: 0.732-0.982) and running (ICC: 0.679-0.985). Conclusion: This study establishes a reliable measurement protocol of three one-way passes when using the ZenoTM Walkway for walking or running analysis. This is the first study to establish reliability of the ZenoTM Walkway during running and in young, active individuals without neuromusculoskeletal pathology. Level of Evidence: 3b.

Longitudinal changes in cognitive and physical function and health-related quality of life in older adults with acute myeloid leukemia.

INTRODUCTION: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments. MATERIALS AND METHODS: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses. RESULTS: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16. DISCUSSION: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML. CLINICAL TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov ID: NCT03226418.

Short-term fear of movement improves less after anterior cruciate ligament reconstruction with concomitant meniscus repair.

BACKGROUND: Psychological response is important in return-to-sport decisions for athletes recovering from anterior cruciate ligament reconstruction (ACLR). The purpose of this study was to compare psychological response after ACLR with a concomitant meniscus repair compared to isolated ACLR. METHODS: Thirty-five individuals completed the Tampa Scale of Kinesiophobia (TSK) and Anterior Cruciate Ligament Return-to-Sport after Injury (ACL-RSI) scale before ACLR and 2, 4, and 6 months after ACLR. Participants were dichotomized based on presence of concomitant meniscus repair (Yes/No). Separate group X time repeated measures analyses of variance were conducted for both scales. RESULTS: Participants were 65.7% female, 19.1 ± 4.7 years old with BMI of 24.9 ± 4.4 kg/m2. Sixteen individuals had an isolated ACLR with 19 individuals having an ACLR with concomitant meniscus repair. For the TSK, there was a group × time interaction effect(p = 0.028), with improvement in TSK scores for the isolated ACLR group (ACLR:2 months = 24.8 ± 3.7; 4 months = 22.0 ± 5.7; 6 months: 19.9 ± 5.9; Meniscus Repair:2 months = 25.5 ± 4.7; 4 months = 24.1 ± 5.0; 6 months: 23.8 ± 4.7). Six months after ACLR, TSK scores were worse in the meniscus repair group(p = 0.036). For the ACL-RSI, there was no interaction(p = 0.07). CONCLUSION: Concomitant meniscus repair with ACLR results in less post-operative improvement in kinesiophobia through 6 months after ACLR compared to isolated ACLR.

Rural and Agricultural Natural Disaster Stress and Recovery: A Comparison.

This study used a novel survey instrument to evaluate the hypothesis that U.S. agricultural producers have significantly different stress and recovery experiences following acute-onset natural disaster compared to their non-agricultural counterparts. Participants were recruited through local organizations and targeted email and social media in communities in Arkansas and Nebraska that had experienced violent tornadoes in 2014 and/or severe flooding in 2019. The survey instrument incorporated the Brief Resilience Scale, the Revised Impact of Event Scale referencing two time points, the Posttraumatic Growth Inventory-Short Form, and original questions. Demographic, exposure, stress, and recovery measures were analyzed in SAS with Chi-square tests, t-tests, Wilcoxon tests, and multiple linear regression modeling to test for differences between agricultural and non-agricultural groups in resilience, event exposure, stress symptoms in the week after the event, stress symptoms in the month before the survey, a calculated recovery ratio, and posttraumatic growth. Analysis sample (N = 159) contained 20.8% agricultural occupation, 71.1% female, and 49.1% over age 55. No significant differences were found between agricultural and non-agricultural participants when comparing resilience, stress, or recovery ratio measures. Unadjusted posttraumatic growth score was significantly lower in the agriculture group (P = .02), and an occupation group by sex interaction was significantly associated with posttraumatic growth score (P = .02) when controlled for number of initial posttraumatic stress symptoms in the adjusted model, with agricultural women showing lower growth. Overall, there was no evidence of significant difference in disaster stress and recovery between agricultural and rural, non-agricultural groups in this study. There was some evidence that women in agriculture may have lower levels of recovery. Data indicated that rural residents continue to experience posttraumatic-type symptoms up to 8 years beyond the acute-onset natural disaster events. Communities should include strategies to support mental and emotional health in their preparedness, response, and recovery plans with intentional inclusion of agricultural populations.

Demand and Supply: Association between Pediatric Ethics Consultation Volume and Protected Time for Ethics Work.

BACKGROUND: Despite national increase in pediatric ethics consultation volume over the past decade, protected time and resources for healthcare ethics consultancy work has lagged. METHODS: Correlation study investigating potential associations between ethics consult volume reported by recent national survey of consultants at children's hospitals and five programmatic domains. RESULTS: 104 children's hospitals in 45 states plus Washington DC were included. There was not a statistically significant association between pediatric ethics consult volume and hospital size, rurality of patient population, or number of consultants. Academically-affiliated children's hospitals had fewer ethics consults compared to nonacademically affiliated. Association was found between full-time equivalent (FTE) hours and number of ethics consults (p < 0.0001). Spearman rank correlation between ethics consult volume and FTE was 0.5. CONCLUSIONS: While the results of this study should be interpreted with caution, investment in protected time for ethics consultancy work may translate into increased volume of pediatric ethics consults.

Relationships of serum CC16 levels with smoking status and lung function in COPD.

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. METHODS: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. RESULTS: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj < 0.0001). CONCLUSIONS: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.

Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia.

INTRODUCTION: Survival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection. MATERIALS AND METHODS: In a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach. RESULTS: Broad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0-9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). One-year overall survival was 66% (95% CI 60-87%). DISCUSSION: Our data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials.

Geospatial Distribution of Age-Adjusted Incidence of the Three Major Types of Pediatric Cancers and Waterborne Agrichemicals in Nebraska.

This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age-adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio-economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 µg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000-0.0002 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24-8.54), leukemia (IRR = 7.35; 95% CI: 7.22-7.48), and lymphoma (IRR = 5.59; CI: 5.48-5.69) after adjusting for atrazine groundwater concentration and the county socio-economic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.

Limited-Montage EEG as a Tool for the Detection of Nonconvulsive Seizures.

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.

Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review.

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.

An assessment of factors associated with neurocognitive decline in people living with HIV.

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.

Preferences of adults with cancer for systemic cancer treatment: do preferences differ based on age?

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 (<60 years) versus older adults (≥60 years). Results: While 56% of patients would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Oral instead of intravenous treatment (p = 0.003), shorter hospital stay (p = 0.03), preservation of cognitive function (p = 0.01) and avoidance of pain (p = 0.02) were more important to older patients compared with younger patients. Conclusion: Many patients prioritized maintenance of cognition, functional ability and quality of life; older patients valued oral treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.

Lay abstract Understanding the preferences of adults with cancer is important for physicians to develop personalized cancer treatment plans. We used a self-reported 30-item questionnaire, the Therapy Preference Scale, to help patients express their preferences with regard to safety, efficacy and other aspects of therapy. While 56% of the patients in our study would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Compared with younger patients, older patients preferred oral instead of intravenous treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.

Protocol for a pilot randomised controlled trial of zoledronic acid to prevent bone loss following sleeve gastrectomy surgery.

INTRODUCTION: Sleeve gastrectomy (SG) is an increasingly used and effective treatment for obesity; however, the rapid weight loss associated with SG adversely affects bone metabolism predisposing patients to skeletal fragility. Bisphosphonate medications have been evaluated for safety and efficacy in combating bone loss in patients with osteoporosis, but their use in SG-induced bone loss is limited. The goal of this study is to investigate how a one-time infusion of zoledronic acid compares to placebo, in its ability to combat SG-associated bone loss. METHODS AND ANALYSIS: This research protocol is a 9-month, pilot randomized controlled trial (RCT) involving 30 adult SG patients randomised to receive an infusion of either 5 mg of zoledronic acid or placebo, 6 weeks following surgery. To be included participants must be <350 lbs/158.8 kg, free of bone-impacting pathologies or medications, and must have adequate serum calcium and vitamin D levels at baseline. The primary outcome is change in areal bone mineral density (aBMD) at the total hip. Secondary outcomes include change in aBMD of the femoral neck, and lumbar spine, and change in volumetric BMD at the lumbar spine. The primary aim will be tested using a linear mixed model fit with total hip aBMD at 9 months as the outcome. Treatment, participant sex and menopausal status will be considered in analysis. Groups will be compared using contrast statements at 9 months, with change over 9 months being the primary comparison. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the University of Nebraska Medical Center (IRB820-19). Written consent will be obtained from participants at enrolment by trained staff. Careful and thorough explanation are used in obtainment of consent and voluntariness is emphasised throughout the trial. The findings of this study will be presented locally, nationally, and published in peer-reviewed journals. Additional details will be reported on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04279392.

Mucin Expression and Splicing Determine Novel Subtypes and Patient Mortality in Pancreatic Ductal Adenocarcinoma.

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.

A Type III Hybrid Effectiveness-Implementation Pilot Trial Testing Dissemination and Implementation Strategies for a Pediatric Weight Management Intervention: The Nebraska Childhood Obesity Research Demonstration Project.

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 delivered by an interdisciplinary team in a hospital or medical center. The degree to which these efficacious PWMIs have been translated to, and are feasible in, rural or micropolitan areas is unclear. This study protocol describes a pilot Type III hybrid effectiveness-implementation (T3HEI) trial testing a multilevel strategy that focuses on the adoption, implementation, and sustainability of a PWMI online training program and resource package designed for implementation in micropolitan and rural areas. Methods: The trial design employed the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate outcomes and the Promoting Action on Research Implementation in Health Services framework to specify potential mechanisms of adoption, implementation, and sustainability. The study will test the feasibility of a fund and contract dissemination strategy in the adoption of a PWMI in four to eight rural communities, compare a learning collaborative implementation strategy including embedded training and sustainability action planning with communities who receive the PWMI online program and resources alone, and determine whether the PWMI reach, effectiveness, and maintenance are of magnitude similar to previous effectiveness trials. The dissemination and implementation process focused on an integrated research-practice partnership process model that includes a systems-based approach with multiple sectors and vertical decision-making representation. Conclusions: Our pilot T3HEI study has the potential to inform how best to move and sustain evidence-based PWMIs into practice. The findings will inform larger scale dissemination, implementation, and sustainability efforts in medically underserved areas across the country. Trial registration: This protocol is registered with clinicaltrials.gov (NCT04719442).

Neurocognitive impairment and health-related quality of life among people living with Human Immunodeficiency Virus (HIV).

The association between HIV-associated neurocognitive impairment (NCI) and health-related quality of life (HRQoL) is not well known. We investigated this association among the CNS (Central Nervous System) HIV Antiretroviral Therapy Effects Research (CHARTER) study participants. We performed factor analysis to distinguish physical and mental HRQoL, followed by general linear models. We analyzed 1,340 HIV participants, including 35.6% with NCI, 77.2% males, 70.5% unemployed, and 42.2% with depression. Impaired participants had lower (worse) mental and physical HRQoL mean scores compared to unimpaired participants. NCI was negatively associated with mental HRQoL in crude (mean difference: -4.38; 95% CI: -6.70 to -2.06) and adjusted analysis (-2.56, -4.83 to -0.30). NCI was also negatively associated with physical HRQoL in unadjusted analysis (-4.62, -7.45 to -1.78), though the association weakened in the adjusted analysis (-2.20, -4.81 to 0.40). The association between NCI and HRQoL was confounded mainly by employment and was partially mediated by depression. These findings suggest that future strategies aimed at improving HRQoL among HIV-infected patients with NCI might benefit from concurrent management of depression.

Neurocognitive status and risk of mortality among people living with human immunodeficiency virus: an 18-year retrospective cohort study.

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.

Development and validation of the Therapy Preference Scale to understand patients´ systemic cancer treatment preferences.

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.