Search

Abstract Background The COVID-19 pandemic brought greater focus to the rural mortality penalty in the U.S., which describes the greater mortality rate in rural compared to urban areas. Although it is widely thought that issues such as access to care, age structure of the population, and differences in behavior are likely drivers of the rural mortality penalty, few studies have attempted to tie delayed access to care in rural populations to healthcare outcomes quantitatively. Therefore, it is critical to try and understand these factors to enable more effective public health policy. Methods We performed a cross-sectional analysis of a population of patients with COVID-19 who were admitted to hospitals in the United States between 3/1/2020 and 2/26/2023 to better understand factors leading to outcome disparities amongst groups that all had some level of access to hospital care. Nevertheless, it is widely thought that rural populations often experience delayed access to care, due to transportation and other constraints. Therefore, we hypothesized that deteriorated patient condition at admission likely explained some of the observed difference in mortality between rural and urban populations. Results Our results supported our hypothesis, showing that the rural mortality penalty persists in this population and that by multiple measures, rural patients were likely to be admitted in worse condition, had worse overall health, and were older. Conclusions Although the pandemic threw the rural mortality penalty into sharp relief, it is important to remember that it existed prior to the pandemic and will continue to exist until effective interventions are implemented. This study demonstrates the critical need to address the underlying factors that resulted in rural-dwelling patients being admitted to the hospital in worse condition than their urban-dwelling counterparts during the COVID-19 pandemic, which likely affected other healthcare outcomes as well.

Background: Despite advances in the early detection and treatment of breast cancer (BC), inequity persists, and the BC mortality rate remains approximately 40% higher among Black and African American (B/AA) women compared to White (W) women. Methods: In response to The University of Kansas Cancer Center’s Catchment Area Steering Committee identified priorities, the Breast Cancer Health Equity Task Force (BCHETF) leveraged data-driven insights to develop targeted interventions that promote BC prevention and early detection among B/AA women. Results: By synthesizing data, we mapped census tracts with high B/AA population density to identify targeted areas to focus screening and outreach efforts with an evidence-based intervention (EBI). The BCHETF and researchers are also engaged in ongoing projects to explore patient-level experiences of BC care among B/AA women through focus groups and address provider-level gaps in the delivery of BC risk assessment and screening with telementoring and practice facilitation. Discussion: Targeting efforts through data visualization has been helpful, but limitations remain. Here, we describe the BCHETFs concerted and ongoing efforts to address BC health disparities among B/AA women, facilitate improvements in BC screening access and outcomes, and promote health equity for all.

Background: Lung cancer is the leading cause of cancer related deaths. In Kansas, where coal-fired power plants account for 34% of power, we investigated whether hosting counties had higher age-adjusted lung cancer incidence rates. We also examined demographics, poverty levels, percentage of smokers, and environmental conditions using spatial analysis.Methods: Data from the Kansas Health Matters, and the Behavioral Risk Factor Surveillance System (2010–2014) for 105 counties in Kansas were analyzed. Multiple Linear Regression (MLR) assessed associations between risk factors and age-adjusted lung cancer incidence rates while Geographically Weighted Regression (GWR) examined regional risk factors.Results: Moran’s I test confirmed spatial autocorrelation in age-adjusted lung cancer incidence rates (p

Introduction: Patients without insurance often wait until their symptoms become severe before seeking treatment. While done to avoid the cost of preventative care, this decision leads to uninsured patients presenting with more advanced diseases.Hypothesis: We aim to calculate the overall uninsured rate for cancer patients across The University of Kansas Cancer Center's (KUCC) catchment area and estimate the uninsured rate for patients treated within a large health system in the state of Kansas.Methods: Three datasets were used to generate an overall uninsured rate for both states for the age groups of 0-19, 20-64, and 65 or older. The cancer incidence was derived using the 2020 estimated number of KUCC cases and the mean percentage of 2015-2019 cases for the corresponding age groups. The estimated uninsured and cancer incidence rates were then used to calculate the overall uninsured cancer rate.Results: The total number of estimated 2020 KUCC cases was 24,412, with 0.86%, 42.56%, and 56.58% being the percentage per the age groups 0-19, 20-64, and 65+. The estimated uninsured rate per age group was 5.33%, 13.49%, and 0.40%. This yielded an overall uninsured cancer rate of 6.01%.

Background: Clinical trial participation can improve overall survival and mitigate healthcare disparities for gynecologic cancer patients in low-volume community centers. This study aimed to assess the effectiveness of a centrally regulated but administratively decentralized electronic screening log system to identify eligible patients across a large catchment area for a National Cancer Institute (NCI)-designated cancer center's open clinical trials. Methods: Electronic screening log data collected between 2014 and 2021 from ten community partner sites in a single NCI-designated cancer center's catchment area were reviewed retrospectively. Clinical factors assessed included cancer site, primary versus recurrent disease status, and histology. Identification efficiency (the ratio of patients screened identified with an available trial) was calculated. Identification inefficiencies (failures to identify patients with a potentially relevant trial) were assessed, and etiologies were characterized. Results: Across ten community partner sites, 492 gynecologic cancer patients were screened for seven open clinical trials during the study period. This included 170 (34.5 %) ovarian cancer patients, 156 (31.7 %) endometrial cancer patients, and 119 (24.2 %) cervical cancer patients. Over 40 % had advanced stage disease, and 10.6 % had recurrent disease. Only three patients were identified as having a relevant open trial; none ultimately enrolled due to not meeting trial eligibility criteria. An additional 2–52 patients were retrospectively found to have a relevant trial available despite not being identified as such within the electronic screening log system. Up to 14.4 % of patients had one or more missing minimum data elements that hindered full evaluation of clinical trial availability. Re-screening patients when new trials open may identify 12-15 additional patients per recurrent disease trial. Conclusions: An electronic screening log system can increase awareness of gynecologic oncology clinical trials at a NCI-designated cancer center's community partner sites. However, it is inadequate as a single intervention to increase clinical trial enrollment. Providing adequate support staff, documenting clinical factors consistently, re-screening patients at relevant intervals, and coordinating with central study personnel may increase its utility.

Introduction: Slow patient accrual in cancer clinical trials is always a concern. In 2021, the University of Kansas Comprehensive Cancer Center (KUCC), an NCI-designated comprehensive cancer center, implemented the Curated Cancer Clinical Outcomes Database (C3OD) to perform trial feasibility analyses using real-time electronic medical record data. In this study, we proposed a Bayesian hierarchical model to evaluate annual cancer clinical trial accrual performance. Methods: The Bayesian hierarchical model uses Poisson models to describe the accrual performance of individual cancer clinical trials and a hierarchical component to describe the variation in performance across studies. Additionally, this model evaluates the impacts of the C3OD and the COVID-19 pandemic using posterior probabilities across evaluation years. The performance metric is the ratio of the observed accrual rate to the target accrual rate. Results: Posterior medians of the annual accrual performance at the KUCC from 2018 to 2023 are 0.233, 0.246, 0.197, 0.150, 0.254, and 0.340. The COVID-19 pandemic partly explains the drop in performance in 2020 and 2021. The posterior probability that annual accrual performance is better with C3OD in 2023 than pre-pandemic (2019) is 0.935. Conclusions: This study comprehensively evaluates the annual performance of clinical trial accrual at the KUCC, revealing a negative impact of COVID-19 and an ongoing positive impact of C3OD implementation. Two sensitivity analyses further validate the robustness of our model. Evaluating annual accrual performance across clinical trials is essential for a cancer center. The performance evaluation tools described in this paper are highly recommended for monitoring clinical trial accrual.

OBJECTIVES/GOALS: Frontiers CTSI developed applications to ensure its science teams have technological tools to advance their community engagement and trial management. The Trial Finder app is a mobile application that allows users to navigate available trials. The Accrual app will help study teams monitor their recruitment performances in real time. METHODS/STUDY POPULATION: The Data Science team at the University of Kansas Medical Center (KUMC) had previously developed similar applications for The University of Kansas Cancer Center. Both retrieve information from KUMC’s clinical trial management system and ClinicalTrials.gov. This was replicated to include KUMC Pulmonary Critical Care (PCC) and KUMC Neuromuscular (NM) trials. Frontiers CTSI is working with both groups for piloting and feedback. Recruiting and marketing strategies for investigators to add their trials to both apps will be done through existing communication channels and be highlighted on Frontiers trial resource website. Recruiting and marketing strategies of the Frontiers Trial Finder app to the external community will have a focus on, but not limited to, paid social media advertising. RESULTS/ANTICIPATED RESULTS: The Trial Finder app can help providers search for trials their patient may be eligible for during clinic visits and to engage with the community by allowing anyone to download and browse on their Android/iOS device. Built in REDCap forms are used to capture contact information. The Accrual app is a web-based application that helps study teams monitor their recruitment performances in real time and provide an opportunity to adjust strategies. It uses an in-house algorithm to predict if trials will meet timeline goals. This data is conveniently laid out on a single web page so that science teams can overview all their trials’ recruitment performances simultaneously. The next phase of developing these applications is to market their use within Frontiers CTSI and its community catchment area. DISCUSSION/SIGNIFICANCE: Through collaboration, Frontiers CTSI is developing resources to support community engagement and trial management. New innovative applications like these ensure all the main stakeholders involved with clinical trial execution are always engaged and have access to iterative contemporary technologies that support their research.

OBJECTIVES/GOALS: In 2021, Frontiers CTSI revamped its evaluation infrastructure to be comprehensive, efficient, and transparent in demonstrating outputs and outcomes. We sought to build a platform to standardize measures across program areas, integrate continuous improvement processes into operations, and reduce the data entry burden for investigators. METHODS/STUDY POPULATION: To identify useful metrics, we facilitated each Core’s creation of a logic model, in which they identified all planned activities, expected outputs, and anticipated outcomes for the 5-year cycle and beyond. We identified appropriate metrics based on the logic models and aligned metrics across programs against extant administrative data. We then built a data collection and evaluation platform within REDCap to capture user requests, staff completion of requests, and, ultimately, request outcomes. We built a similar system to track events, attendance, and outcomes. Aligning with other hubs, we also transitioned to a membership model. Membership serves as the backbone of the evaluation platform and allows us to tailor communication, capture demographic information, and reduce the data entry burden for members. RESULTS/ANTICIPATED RESULTS: The Frontiers Evaluation Platform consists of 9 redcap projects with distinct functions and uses throughout the Institute. Point-of-service collection forms include the Consultation Request Event Tracking. Annual Forms include a Study Outcome, Impact, and Member Assessment Survey. Set timepoint collections include K & T application, Mock Study Section, and Pilot grant application submission, review, and outcomes. Flight Tracker is used to collect scientific outcomes and integrated with the platform. Using SQL, the membership module has been integrated into all forms to check and collect membership before service access and provide relevant member data to navigators. All relevant data is then synched into a dashboard for program leadership and management to track outputs and outcomes in real-time. DISCUSSION/SIGNIFICANCE: Since the launch of the evaluation platform in Fall 2022, Frontiers has increased its workflow efficiency and streamlined continuous improvement communication. The platform can serve as a template for other hubs to build efficient processes to create comprehensive and transparent evaluation plans.

Background: Response adaptive randomization is popular in adaptive trial designs, but the literature detailing its execution is lacking. These designs are desirable for patients/stakeholders, particularly in comparative effectiveness research, due to the potential benefits including improving participant buy-in by providing more participants with better treatment during the trial. Frequentist approaches have often been used, but adaptive designs naturally fit the Bayesian methodology; it was developed to deal with data as they come in by updating prior information. Methods: PAIN-CONTRoLS was a comparative-effectiveness trial utilizing Bayesian response adaptive randomization to four drugs, nortriptyline, duloxetine, pregabalin, or mexiline, for cryptogenic sensory polyneuropathy (CSPN) patients. The aim was to determine which treatment was most tolerable and effective in reducing pain. Quit and efficacy rates were combined into a utility function to develop a single outcome, which with treatment sample size, drove the adaptive randomization. Prespecified interim analyses allowed the study to stop for early success or update the randomization probabilities to the better-performing treatments. Results: Seven adaptations to the randomization occurred before the trial ended due to reaching the maximum sample size, with more participants receiving nortriptyline and duloxetine. At the end of the follow-up, nortriptyline and duloxetine had lower probabilities of participants that had stopped taking the study medication and higher probabilities were efficacious. Mexiletine had the highest quit rate, but had an efficacy rate higher than pregabalin. Conclusions: Response adaptive randomization has become a popular trial tool, especially for those utilizing Bayesian methods for analyses. By illustrating the execution of a Bayesian adaptive design, using the PAIN-CONTRoLS trial data, this paper continues the work to provide literature for conducting Bayesian response adaptive randomized trials.

Abstract Background This research study aimed to evaluate the financial burden among older cancer patients and its corresponding risk factors. Factors such as increasing treatment costs and work limitations often lead cancer patients to bankruptcy and poor quality of life. These consequences, in turn, can cause higher mortality rates among these patients. Methods This retrospective cohort study utilized data from the Health Retirement Study (HRS), conducted by the University of Michigan (N = 18,109). Eligible participants had responses captured from years 2002 to 2016. Participants were classified according to any self‐reported cancer diagnosis (yes or no) and were compared on the basis of financial, work, and health‐related outcomes. Propensity score (PS) matching was applied to reduce the effects of potential confounding factors. Also only, individuals with an age ≥50 and ≤85 during Wave 6 were retained. Results Multivariate analysis with random effects revealed several indicators of financial burden when comparing participants with a cancer diagnosis to those with no history of cancer. Mean out‐of‐pocket costs associated with a cancer diagnosis were $1058 higher when compared to participants with no history of cancer, suggesting that even cancer patients with insurance coverage faced out‐of‐pocket costs. Respondents with cancer patients had higher odds of encountering financial hardship if they are facing Work Limitations (OR = 2.714), Regular use of Medications (OR = 2.518), Hospital Stays (OR = 2.858), Declining Health (OR = 2.349), or were being covered under government health insurance (OR = 5.803) than respondents who did not have cancer, or suffered from mental health issues such as Depression (OR = 0.901). Conclusion Cancer patients contend with increasing financial costs during their treatment. However, most newly diagnosed patients are not aware of these costs and are given few resources to handle them.

Abstract Background Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint. Methods In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67). Results We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint. Discussion Our approach balances trial speed and the need for information on the single, key secondary endpoint.

Objective The gold standard for breast cancer screening and prevention is regular mammography; thus, understanding what impacts adherence to this standard is essential in limiting cancer-associated costs. We assessed the impact of various understudied sociodemographic factors of interest on adherence to the receipt of regular mammograms. Methods A total N c = 14,553 mammography-related claims from N w = 6,336 female Kansas aged between 45 and 54 were utilized from insurance claim databases furnished by multiple providers. Adherence to regular mammography was quantified continuously via a compliance ratio, used to capture the number of eligible years in which at least one mammogram was received, as well as categorically. The relationship between race, ethnicity, rurality, insurance (public/private), screening facility type, and distance to nearest screening facility with both continuous and categorically defined compliance were individually assessed via Kruskal–Wallis one-way ANOVAs, chi-squared tests, multiple linear regression models, and multiple logistic regression, as appropriate. Findings from these individual models were used to inform the construction of a basic, multifaceted prediction model. Results Model results demonstrated that all factors race and ethnicity had at least some bearing on compliance with screening guidelines among mid-life female Kansans. The strongest signal was observed in the rurality variable, which demonstrated a significant relationship with compliance regardless of how it was defined. Conclusion Understudied factors that are associated with regular mammography adherence, such as rurality and distance to nearest facility, may serve as important considerations when developing intervention strategies for ensuring that female patients stick to prescribed screening regimens.

BackgroundStudying patients’ social needs is critical to the understanding of health conditions and disparities, and to inform strategies for improving health outcomes. Studies have shown that people of color, low-income families, and those with lower educational attainment experience greater hardships related to social needs. The COVID-19 pandemic represents an event that severely impacted people’s social needs. This pandemic was declared by the World Health Organization on March 11, 2020, and contributed to food and housing insecurity, while highlighting weaknesses in the health care system surrounding access to care. To combat these issues, legislators implemented unique policies and procedures to help alleviate worsening social needs throughout the pandemic, which had not previously been exerted to this degree. We believe that improvements related to COVID-19 legislature and policy have positively impacted people’s social needs in Kansas and Missouri, United States. In particular, Wyandotte County is of interest as it suffers greatly from issues related to social needs that many of these COVID-19–related policies aimed to improve. ObjectiveThe research objective of this study was to evaluate the change in social needs before and after the COVID-19 pandemic declaration based on responses to a survey from The University of Kansas Health System (TUKHS). We further aimed to compare the social needs of respondents from Wyandotte County from those of respondents in other counties in the Kansas City metropolitan area. MethodsSocial needs survey data from 2016 to 2022 were collected from a 12-question patient-administered survey distributed by TUKHS during a patient visit. This provided a longitudinal data set with 248,582 observations, which was narrowed down into a paired-response data set for 50,441 individuals who had provided at least one response before and after March 11, 2020. These data were then bucketed by county into Cass (Missouri), Clay (Missouri), Jackson (Missouri), Johnson (Kansas), Leavenworth (Kansas), Platte (Missouri), Wyandotte (Kansas), and Other counties, creating groupings with at least 1000 responses in each category. A pre-post composite score was calculated for each individual by adding their coded responses (yes=1, no=0) across the 12 questions. The Stuart-Maxwell marginal homogeneity test was used to compare the pre and post composite scores across all counties. Additionally, McNemar tests were performed to compare responses before and after March 11, 2020, for each of the 12 questions across all counties. Finally, McNemar tests were performed for questions 1, 7, 8, 9, and 10 for each of the bucketed counties. Significance was assessed at P

Abstract Background Rural residence is commonly thought to be a risk factor for poor cancer outcomes. However, a number of studies have reported seemingly conflicting information regarding cancer outcome disparities with respect to rural residence, with some suggesting that the disparity is not present and others providing inconsistent evidence that either urban or rural residence is associated with poorer outcomes. We suggest a simple explanation for these seeming contradictions: namely that rural cancer outcome disparities are related to factors that occur differentially at a local level, such as environmental exposures, lack of access to care or screening, and socioeconomic factors, which differ by type of cancer. Methods We conducted a retrospective cohort study examining ten cancers treated at the University of Kansas Medical Center from 2011 to 2018, with individuals from either rural or urban residences. We defined urban residences as those in a county with a U.S. Department of Agriculture Urban Influence Code (UIC) of 1 or 2, with all other residences defines a rural. Inverse probability of treatment weighting was used to create a pseudo-sample balanced for covariates deemed likely to affect the outcomes modeled with cumulative link and weighted Cox-proportional hazards models. Results We found that rural residence is not a simple risk factor but rather appears to play a complex role in cancer outcome disparities. Specifically, rural residence is associated with higher stage at diagnosis and increased survival hazards for colon cancer but decreased risk for lung cancer compared to urban residence. Conclusion Many cancers are affected by unique social and environmental factors that may vary between rural and urban residents, such as access to care, diet, and lifestyle. Our results show that rurality can increase or decrease risk, depending on cancer site, which suggests the need to consider the factors connected to rurality that influence this complex pattern. Thus, we argue that such disparities must be studied at the local level to identify and design appropriate interventions to improve cancer outcomes.

Background: The study startup process for interventional clinical trials is a complex process that involves the efforts of many different teams. Each team is responsible for their startup checklist in which they verify that the necessary tasks are done before a study can move on to the next team. This regulatory process provides quality assurance and is vital for ensuring patient safety [10]. However, without having this startup process centralized and optimized, study approval can take longer than necessary as time is lost when it passes through many different hands. Objective: This manuscript highlights the process and the systems that were developed at The University of Kansas Comprehensive Cancer Center regarding the study startup process. To facilitate this process the regulatory management, site development, cancer center administration, and the Biostatistics & Informatics Shared Resources (BISR) teams came together to build a platform aimed at streamlining the startup process and providing a transparent view of where a study is in the startup process. Process: Ensuring the guidelines are clearly articulated for the review criteria of each of the three review boards, i.e., Disease Working Group (DWG), Executive Resourcing Committee (ERC), and Protocol Review and Monitoring Committee (PRMC) along with a system that can track every step and its history throughout the review process. Results: Well-defined processes and tracking methodologies have allowed the operations teams to track each study closely and ensure the 90-day and 120-day deadlines are met, this allows the operational team to dynamically prioritize their work daily. It also provides Principal investigators a transparent view of where their study stands within the study startup process and allows them to prepare for the next steps accordingly. Conclusion/future work: The current process and technology deployment has been a significant improvement to expedite the review process and minimize study startup delays. There are still a few opportunities to fine-tune the study startup process; an example of which includes automatically informing the operational managers or the study teams to act upon deadlines regarding study review rather than the current manual communication process which involves them looking it up in the system which can add delays.

BackgroundThe National Clinical Trials Network program conducts phase 2 or phase 3 treatment trials across all National Cancer Institute’s designated cancer centers. Participant accrual across these clinical trials is a critical factor in deciding their success. Cancer centers that cater to rural populations, such as The University of Kansas Cancer Center, have an additional responsibility to ensure rural residents have access and are well represented across these studies. ObjectiveThere are scant data available regarding the factors that act as barriers to the accrual of rural residents in these clinical trials. This study aims to use electronic screening logs that were used to gather patient data at several participating sites in The Kansas University of Cancer Center’s Catchment area. MethodsScreening log data were used to assess what clinical trial participation barriers are faced by these patients. Additionally, the differences in clinical trial participation barriers were compared between rural and urban participating sites. ResultsAnalysis revealed that the hospital location rural urban category, defined as whether the hospital was in an urban or rural setting, had a medium effect on enrolment of patients in breast cancer and lung cancer trials (Cohen d=0.7). Additionally, the hospital location category had a medium effect on the proportion of recurrent lung cancer cases at the time of screening (d=0.6). ConclusionsIn consideration of the financially hostile nature of cancer treatment as well as geographical and transportation barriers, clinical trials extended to rural communities are uniquely positioned to alleviate the burden of nonmedical costs in trial participation. However, these options can be far less feasible for patients in rural settings. Since the number of patients with cancer who are eligible for a clinical trial is already limited by the stringent eligibility criteria required of such a complex disease, improving accessibility for rural patients should be a greater focus in health policy.

Objective: Participant recruitment is a challenge for any clinical trial but is especially complex in cancer specifically due to the need to initiate treatment urgently. Most participants enrolled in oncology clinical trials are identified as potential participants by the oncologist or other referring provider. Optimal clinical care for patients with cancer includes consideration of participation in a clinical trial. However, the process of finding a clinical trial that is appropriate the patient can be cumbersome and time consuming. Material and Methods: The University of Kansas Cancer Center has developed a mobile application (app) which streamlines the clinical trial search process for physicians, patients, and caregivers by cohesively integrating all clinical trials currently recruiting in the center and making them easy to browse. Results: Key aspects of the app include simple filtering options, the ability to search for trials by name, easily accessible assistance, and in-app referral by phone or email. Initial feedback on the app has been very positive, with several suggestions already being implemented in future development. The app was designed to be used both by physicians to find trials, as well as patients in collaboration with their physicians. Conclusion: While long-term results will be crucial to understanding how the app can best serve our patient population, our initial results suggest that health system specific clinical trial apps can address a currently unmet need in the clinical trial recruitment process.

BackgroundAs the cost of clinical trials continues to rise, novel approaches are required to ensure ethical allocation of resources. Multisite trials have been increasingly utilized in phase 1 trials for rare diseases and in phase 2 and 3 trials to meet accrual needs. The benefits of multisite trials include easier patient recruitment, expanded generalizability, and more robust statistical analyses. However, there are several problems more likely to arise in multisite trials, including accrual inequality, protocol nonadherence, data entry mistakes, and data integration difficulties. ObjectiveThe Biostatistics & Data Science department at the University of Kansas Medical Center developed a clinical trial management system (comprehensive research information system [CRIS]) specifically designed to streamline multisite clinical trial management. MethodsA National Institute of Child Health and Human Development–funded phase 3 trial, the ADORE (assessment of docosahexaenoic acid [DHA] on reducing early preterm birth) trial fully utilized CRIS to provide automated accrual reports, centralize data capture, automate trial completion reports, and streamline data harmonization. ResultsUsing the ADORE trial as an example, we describe the utility of CRIS in database design, regulatory compliance, training standardization, study management, and automated reporting. Our goal is to continue to build a CRIS through use in subsequent multisite trials. Reports generated to suit the needs of future studies will be available as templates. ConclusionsThe implementation of similar tools and systems could provide significant cost-saving and operational benefit to multisite trials. Trial RegistrationClinicalTrials.gov NCT02626299; https://tinyurl.com/j6erphcj

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014).For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child.Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

The primary goal for any clinical trial after it receives a funding notification is to receive regulatory approval and initiate the trial for recruitment. Every trial must go through documentation and regulatory process before it can start recruiting participants and collecting data; this initial process of review and approval is known as the study start-up process (SSU). We evaluated the average time taken for studies to receive approvals. Using data from clinical trials conducted at the University of Kansas Medical Center, various times to reach the start of the study were calculated based on the dates of individual study. The results of this analysis showed that chart review studies and investigator-initiated trials had a shorter time to activation than other types of studies. Additionally, single-center studies had a shorter activation time than multi-center studies. The analysis also demonstrated that the overall processing time consistently had been reduced over time.

The role of the brainstem cholinergic system in the regulation of sleep-wake states has been studied extensively but relatively little is known about the role of cholinergic mechanisms in prefrontal cortex in the regulation of sleep-wake states. In a recent study, we showed that prefrontal cholinergic stimulation in anesthetized rat can reverse the traits associated with anesthesia and restore a wake-like state, thereby providing evidence for a causal role for prefrontal cholinergic mechanisms in modulating level of arousal. However, the effect of increase in prefrontal cholinergic tone on spontaneous sleep-wake states has yet to be demonstrated. Therefore, in this study, we tested the hypothesis that delivery of cholinergic agonists – carbachol or nicotine – into prefrontal cortex of rat during slow wave sleep (SWS) would produce behavioral arousal and increase the time spent in wake state. We show that unilateral microinjection (200 nL) of carbachol (1 mM) or nicotine (100 mM) into prefrontal cortex during SWS decreased the latency to the onset of wake state (p = 0.03 for carbachol, p = 0.03 for nicotine) and increased the latency to the onset of rapid eye movement sleep (p = 0.008 for carbachol, p = 0.006 for nicotine). Although the infusion of 1 mM carbachol increased the time spent in wake state (p = 0.01) and decreased the time spent in SWS (p = 0.01), infusion of 10 or 100 mM nicotine did not produce any statistically significant change in sleep-wake architecture. These data demonstrate a differential role of prefrontal cholinergic receptors in modulating spontaneous sleep-wake states.

There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to correlate with the level of consciousness during anesthesia. In this study, we used Lempel-Ziv complexity (LZc) to characterize frontal and parietal electroencephalographic complexity (0.5–175 Hz, 0.5–55 Hz, 65–175 Hz) before, during, and after ketamine or propofol anesthesia in the rat. To control for the potential influence of spectral changes in complexity estimation, LZc was normalized with phase-shuffled surrogate data. We demonstrate that ketamine and propofol anesthesia were characterized by a significant reduction in broadband (0.5–175 Hz) LZc. Further analysis showed that while the reduction of LZc during ketamine anesthesia was significant in 65–175 Hz range, during propofol anesthesia, a significant decrease was observed in 0.5–55 Hz bandwidth. LZc in broadband and 0.5–55 Hz range showed a significant increase during emergence from ketamine anesthesia. Phase-shuffled normalized LZc revealed that (1) decrease in complexity during ketamine and propofol anesthesia—not increase in complexity during emergence—were dissociable from the influence of spectral changes, and (2) reduced LZc during ketamine anesthesia was present across all three bandwidths. Ketamine anesthesia was characterized by reduced complexity in high gamma bandwidth, as reflected in both raw and phase-shuffled normalized LZc, which suggests that reduced high gamma complexity is a neurophysiological feature of ketamine anesthesia.

1. Abstract: Early phase clinical trials are the first step in testing new medications and therapeutics developed by clinical and biomedical investigators. These trials aim to find a safe dose of a newly targeted drug (phase I) or find out more about the side effects and early signals of treatment efficacy (phase II). In a research institute, many biomedical investigators in oncology are encouraged to initiate such trials early in their careers as part of developing their research portfolio. These investigator-initiated trials (IITs) are funded internally by the University of Kansas Cancer Center or partially funded by pharmaceutical companies. As financial, administrative, and practical considerations play an essential role in the successful completion of IITs, it is imperative to efficiently allocate resources to plan, design, and execute these studies within the allotted time. This manuscript describes monitoring tools and processes to improve the efficiency, cost-effectivness, and reliability of IITs. The contributions of this team to processes such as: participant recruitment, feasibility analysis, clinical trial design, accrual monitoring, data management, interim analysis support, and final analysis and reporting are described in detail. This manuscript elucidates how, through the aid of technology and dedicated personnel support, the efficiency of IIT-related processes can be improved. Early results of these initiatives look promising, and the Biostatistics and Informatics team intends to continue fostering innovative methodologies to enhance cancer research by improving the efficiency of IITs.

Abstract Background Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Methods Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients’ perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). Discussions Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. Trial registration ClinicalTrials.gov Identifier: NCT03133793; Data of Registration: April 28, 2017.

To fully support their role in translational and personalized medicine, biorepositories and biobanks must continue to advance the annotation of their biospecimens with robust clinical and laboratory data. Translational research and personalized medicine require well-documented and up-to-date information, but the infrastructure used to support biorepositories and biobanks can easily be out of sync with the host institution. To assist researchers and provide them with accurate pathological, epidemiological, and bio-molecular data, the Biospecimen Repository Core Facility (BRCF) at the University of Kansas Medical Center (KUMC) merges data from medical records, the tumor registry, and pathology reports using the Curated Cancer Clinical Outcomes Database (C3OD). In this report, we describe the utilization of C3OD to optimally retrieve and dispense biospecimen samples using these 3 data sources and demonstrate how C3OD greatly increases the efficiency of obtaining biospecimen samples for the researchers.

Studies from human and non-human species have demonstrated a breakdown of functional corticocortical connectivity during general anesthesia induced by anesthetics with diverse molecular, neurophysiological, and pharmacological profiles. Recent studies have demonstrated that changes in long-range neural communication, and by corollary, functional connectivity, might be influenced by cross-frequency coupling (CFC) between the phase of slow oscillations and the amplitude of local fast oscillations. Phase-amplitude coupling (PAC) between slow oscillations and alpha rhythm during general anesthesia reveal distinct patterns depending on the anesthetic. In this study, we analyzed the effect of three clinically used anesthetics (propofol: n = 6, sevoflurane: n = 10, and ketamine: n = 8) with distinct molecular mechanisms on changes in PAC in the frontal cortex of rat. The loss of righting reflex was used as a surrogate for unconsciousness. PAC was calculated using the modulation index (MI) algorithm between delta (1–4 Hz), theta (4–10 Hz), low gamma (25–55 Hz), and high gamma (65–125 Hz) bands. A linear mixed model with fixed effects was used for statistical comparisons between waking, anesthetized, and post-anesthesia recovery epochs. All three anesthetics increased the coupling between delta and low gamma (p < 0.0001) as well as between theta and low gamma (p < 0.0001) oscillations, which returned to baseline waking levels during the post-anesthetic recovery period. In addition, a reversible reduction in high gamma power (p < 0.0001) was a consistent change during anesthesia induced by all three agents. The changes in delta-high gamma and theta-high gamma PAC as well as power spectral changes in delta, theta, and low gamma bandwidths did not show a uniform response across the three anesthetics. These results encourage the study of alternative PAC patterns as drug-invariant markers of general anesthesia in humans.

We provide a check list of the vascular plants of Theog Forest Division, Himachal Pradesh, Western Himalaya. Himachal Pradesh has been extensively surveyed in terms of flora by a large number of workers, albeit highly confined to prioritized areas. The floristic inventorization resulted in a total of 442 vascular plant species belonging to 311 genera and 117 families from an area of 512 km2. Out of these, 408 species belonged to Angiosperms, 7 to Gymnosperms and 27 to Pteridophytes. The predominant families among Dicotyledons were Asteraceae, Rosaceae and Lamiaceae. Among the Monocotyledons, the most represented family was Poaceae, followed by Liliaceae and Cyperaceae. Pinaceae and Pteridaceae were found to be the most represented families among the Gymnosperms and Pteridophytes, respectively. Species richness was highest in shrubberies, which formed an ideal habitat for many herbaceous species within different habitat types. Strategic eradication of weed species, especially obnoxious species such as Lantana camara and Parthenium hysterophorus is required for effective management in the area.

Nav1.6 is a major voltage-gated sodium channel in the central and peripheral nervous systems. Within neurons, the channel protein is concentrated at the axon initial segment and nodes of Ranvier, where it functions in initiation and propagation of action potentials. We examined the role of Nav1.6 in general anesthesia using two mouse mutants with reduced activity of Nav1.6, Scn8amedJ/medJ and Scn8a9J/9J. The mice were exposed to the general anesthetics isoflurane and sevoflurane in step-wise increments; the concentration required to produce loss of righting reflex, a surrogate for anesthetic-induced unconsciousness in rodents, was determined. Mice homozygous for these mutations exhibited increased sensitivity to both isoflurane and sevoflurane. The increased sensitivity was observed during induction of unconsciousness but not during the recovery phase, suggesting that the effect is not attributable to compromised systemic physiology. Electroencephalographic theta power during baseline waking was lower in mutants, suggesting decreased arousal and reduced neuronal excitability. This is the first report linking reduced activity of a specific voltage-gated sodium channel to increased sensitivity to general anesthetics in vivo.