Barriers to medication adherence in sickle cell disease: A comprehensive theory-based evaluation using the COM-B model.

BACKGROUND: Sickle cell disease (SCD) affects more than 100,000 Americans, with complications such as pain episodes and acute chest syndrome. Despite the efficacy of hydroxyurea in reducing these complications, adherence remains low. Study objectives were to examine barriers to hydroxyurea adherence, and to evaluate the relationship between barriers and their impact on adherence. METHODS: In this cross-sectional study, patients with SCD and their caregivers were enrolled if they were taking hydroxyurea. Study measures included demographics, self-report of adherence using visual analog scale (VAS), and the Disease Management and Barriers Interview (DMI)-SCD. The DMI-SCD was mapped to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. RESULTS: Forty-eight caregivers (females 83%, median age 38 [34-43]) and 19 patients (male 53%, median age 15 [13.5-18]) participated. Using VAS, many patients (63%) reported low hydroxyurea adherence, while most caregivers (75%) reported high adherence. Caregivers endorsed barriers across multiple COM-B components, with physical opportunity (e.g., cost) and reflective motivation (e.g., SCD perceptions) being the most identified categories (48% and 42%), respectively. Patients' most identified barriers included psychological capability (e.g., forgetfulness) and reflective motivation (84% and 68%), respectively. Patients' and caregivers' VAS scores negatively correlated with the number of barriers (rs  = -.53, p = .01; rs  = -.28, p = .05) and COM-B categories (rs  = -.51, p = .02; rs  = -.35, p = .01), respectively, suggesting lower adherence with more endorsed barriers. CONCLUSIONS: Fewer barriers to hydroxyurea adherence were associated with higher adherence. Understanding barriers to adherence is essential to develop tailored interventions aimed at improving adherence.

Inflammation, Executive Function, and Adiposity in Children With or at Risk for Obesity: A Pilot Study.

OBJECTIVE: Obesity is associated with executive function (EF) deficits across the lifespan. Higher body mass index (BMI), obesity severity, and poorer adherence and weight outcomes in obesity treatment have all been associated with EF deficits. Adult literature has begun to emphasize neuroinflammation in obesity as a possible pathway to later cognitive impairment in EF. However, pediatric obesity literature has yet to establish associations between peripheral inflammation and EF. Thus, the present study examined associations and variability in inflammation, EF, and adiposity in children with or at risk for obesity. Additionally, inflammation was examined as a mediator of the relationship between adiposity and EF. METHODS: Children (N = 39) aged 8-12 years with BMI ≥ 50th percentile were recruited. The NIH Toolbox Cognitive Battery was used to assess performance-based EF. Peripheral inflammation was assessed in fasted sera. Dual-energy X-ray absorptiometry scans were conducted to assess body composition. Linear regression and Hayes' PROCESS Model 4 (Hayes, 2017) were used to evaluate associations between adiposity and inflammation, inflammation and EF, and whether adiposity effects EF through its effect on inflammation. RESULTS: Positive associations were identified between adiposity and inflammation, and negative to null associations were identified between inflammation and EF. Medium indirect effects of adiposity on EF through inflammation were detected. CONCLUSION: Pilot evidence suggests greater adiposity is linked with greater inflammation, which in turn is associated with less EF in some domains. Directionality and causality cannot yet be established, but with replication, findings may inform efforts to target EF in pediatric obesity.

Implementation of a women's reproductive behavioral health telemedicine program: a qualitative study of barriers and facilitators in obstetric and pediatric clinics.

BACKGROUND: Perinatal Mood and Anxiety Disorders and Substance Use Disorders are common and result in significant morbidities and mortality. Despite evidence-based treatment availability, multiple barriers exist to care delivery. Because telemedicine offers opportunities to overcome these barriers, the objective of this study was to characterize barriers and facilitators to implementing a mental health and substance use disorder telemedicine program in community obstetric and pediatric clinics. METHODS: Interviews and site surveys were completed with practices engaged in a Women's Reproductive Behavioral Health Telemedicine program (N = 6 sites; 18 participants) at the Medical University of South Carolina and telemedicine providers involved in care delivery (N = 4). Using a structured interview guide based on implementation science principles, we assessed program implementation experiences and perceived barriers and facilitators to implementation. A template analysis approach was used to analyze qualitative data within and across groups. RESULTS: The primary program facilitator was service demand driven by the lack of available maternal mental health and substance use disorder services. Strong commitment to the importance of addressing these health concerns provided a foundation for successful program implementation yet practical challenges such as staffing, space, and technology support were notable barriers. Services were supported by establishing good teamwork within the clinic and with the telemedicine team. CONCLUSION: Capitalizing on clinics' commitment to care for women's needs and a high demand for mental health and substance use disorder services while also addressing resource and technology needs will facilitate telemedicine program success. Study results may have implications for potential marketing, onboarding and monitoring implementation strategies to support clinics engaging in telemedicine programs.

Contribution of Continuous Virtual Monitoring to Hospital Safety, Quality, and Value of Care for COVID-19 Patients.

Introduction: The rapid onset of the COVID-19 pandemic increased hospital admissions and shortages for personal protective equipment (PPE) used to slow the spread of infections. In addition, nurses treating COVID-19 patients have time-consuming guidelines to properly don and doff PPE to prevent the spread. Methods: To address these issues, the Medical University of South Carolina repurposed continuous virtual monitoring (CVM) systems to reduce the need for staff to enter patient rooms. The objective of this study was to identify the economic implications associated with using the CVM program for COVID-19 patients. We employed a time-driven activity-based costing approach to determine time and costs saved by implementing CVM. Results: Over the first 52 days of the pandemic, the use of the CVM system helped providers attend to patients needs virtually while averting 19,086 unnecessary in-person interactions. The estimated cost savings for the CVM program for COVID-19 patients in 2020 were $419,319, not including potential savings from avoided COVID-19 transmissions to health care workers. A total of 19,086 PPE changes were avoided, with savings of $186,661. After accounting for cost of the CVM system, the net savings provided an outstanding return on investment of 20.6 for the CVM program for COVID-19 patient care. Conclusion: The successful and cost saving repurposing of CVM systems could be expanded to other infectious disease applications, and be applied to high-risk groups, such as bone marrow and organ transplant patients.

Building telehealth teams of the future through Interprofessional curriculum development: a five-year mixed methodology study.

Building the next generation of telehealth enabled professionals requires a mixture of team-based, interprofessional practice with novel technologies that connect providers and patients. Effective telehealth education is critical for the development of multidisciplinary training curricula to ensure workforce preparedness. In this study, we evaluated the impact of a formal telehealth education curriculum for interprofessional students through an online elective. Over 12 semesters, 170 students self-selected to enroll in the 3-credit hour interprofessional elective and took part in structured didactic, experiential and interprofessional learning opportunities. Mixed-method assessments show significant knowledge and confidence gains with students reflecting on their roles as future healthcare providers. The results from five years' worth of course data shows not only an opportunity to advance the individual knowledge of trainees, but a larger movement to facilitate changes in practice toward population health goals. Recent global health events have further highlighted the need for a rapid response to public health emergencies by highly trained provider teams who are able to utilize technology as the cornerstone for the continuity of care.

Clinical learning for pre-registration nursing students: a viva voce approach during COVID-19.

The COVID-19 pandemic restricted face-to-face contact between students and educators, limiting continual assessment of student's clinical skill development. This led to rapid transformational online adaptations to nursing education. This article will present and discuss the introduction of a clinical 'viva voce' approach, which has been used at one university to formatively assess students' clinical learning and reasoning skills using virtual methods. The Virtual Clinical Competency Conversation (V3C) was developed using the 'Think aloud approach' and involved facilitated one-to-one discussion based on two questions from a bank of 17 predefined clinically focused questions. A total of 81 pre-registration students completed the formative assessment process. Overall, feedback from students and academic facilitators was positive and facilitated both learning and consolidation in a safe and nurturing way. Further local evaluation is continuing to measure the impact of the V3C approach on student learning now that some aspects of face-to-face education have resumed.

Delineating functional mechanisms of the p53/p63/p73 family of transcription factors through identification of protein-protein interactions using interface mimicry.

Members of the p53 family of transcription factors-p53, p63, and p73-share a high degree of homology; however, members can be activated in response to different stimuli, perform distinct (sometimes opposing) roles and are expressed in different tissues. The level of complexity is increased further by the transcription of multiple isoforms of each homolog, which may interact or interfere with each other and can impact cellular outcome. Proteins perform their functions through interacting with other proteins (and/or with nucleic acids). Therefore, identification of the interactors of a protein and how they interact in 3D is essential to fully comprehend their roles. By utilizing an in silico protein-protein interaction prediction method-HMI-PRED-we predicted interaction partners of p53 family members and modeled 3D structures of these protein interaction complexes. This method recovered experimentally known interactions while identifying many novel candidate partners. We analyzed the similarities and differences observed among the interaction partners to elucidate distinct functions of p53 family members and provide examples of how this information may yield mechanistic insight to explain their overlapping versus distinct/opposing outcomes in certain contexts. While some interaction partners are common to p53, p63, and p73, the majority are unique to each member. Nevertheless, most of the enriched pathways associated with these partners are common to all members, indicating that the members target the same biological pathways but through unique mediators. p63 and p73 have more common enriched pathways compared to p53, supporting their similar developmental roles in different tissues.

Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia.

BACKGROUND: Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real-world implementation in high-income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. PROCEDURE: We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients' electronic medical record. Participants with a hydroxyurea exposure >20 mg/kg/day and ≤20 mg/kg/day were included in the higher and lower exposure groups, respectively. RESULTS: Forty-five participants were included in the analysis (56% male; median age 12 years [range 2-19]; 98% Black). Higher exposed participants (n = 23) were prescribed a higher dose (27.2 vs. 24.4 mg/kg/day, p = .002) and had better adherence (0.92 vs. 0.71, p ≤ .001) compared to lower exposed participants (n = 22). Higher exposure was associated with higher fetal hemoglobin (p = .04) and mean corpuscular volume (p = .02). CONCLUSIONS: Higher hydroxyurea exposure is associated with improved hematologic parameters in the high-income setting and is affected by both prescribed dose and adherence. Future studies are needed to optimize both adherence and hydroxyurea prescribing and confirm that increasing exposure improves clinical outcomes in this setting.

School nurse perception of asthma care in school-based telehealth.

OBJECTIVE: School-based telehealth (SBTH) offers an opportunity to overcome traditional barriers to providing comprehensive asthma care for children. Guided by an implementation science framework considering factors internal and external to the school setting, we characterized barriers and facilitators to asthma care within an existing SBTH program available in over 50 under-resourced South Carolina schools. METHODS: This cross-sectional study assessed barriers and facilitators to SBTH asthma care delivery using web-based surveys of school nurses, specifically addressing school implementation of telehealth methods. Surveys evaluated practices and nurse and school-specific factors related to telehealth implementation including perceived barriers, organizational readiness and self-efficacy. Utilizers were schools who completed 1-10 average visits per month while non-utilizers completed less than 1 average visit per month. Descriptive statistics were performed to characterize perceptions in utilizers versus non-utilizers. RESULTS: Of 53 surveys distributed, 36 were completed (68% response rate). Commonly cited barriers included inadequate time due to competing tasks in both utilizers (65%) and non-utilizers (74%) as well as lack of caregiver involvement in care planning (94% of utilizers and 84% of non-utilizers). Of those utilizing specific, relevant telehealth services, schools scored high in perceptions of organizational readiness (n = 24, mean: 24.5/30), self-efficacy (n = 26, mean: 3.6/5) and comfort with identifying students eligible for SBTH (n = 26, mean: 3.5/5). CONCLUSIONS: We identified inadequate nurse time and challenges engaging caregivers as key barriers to implementation of a school-based telehealth asthma program providing care to an under-resourced population. Addressing these barriers when expanding telehealth services may promote utilization of telehealth.

Proactive Electronic Visits for Smoking Cessation and Chronic Obstructive Pulmonary Disease Screening in Primary Care: Randomized Controlled Trial of Feasibility, Acceptability, and Efficacy.

BACKGROUND: Most smokers with chronic obstructive pulmonary disease (COPD) have not yet been diagnosed, a statistic that has remained unchanged for over two decades. A dual-focused telehealth intervention that promotes smoking cessation, while also facilitating COPD screening, could help address national priorities to improve the diagnosis, prevention, treatment, and management of COPD. The purpose of this study was to preliminarily evaluate an integrated asynchronous smoking cessation and COPD screening e-visit (electronic visit) that could be delivered proactively to adult smokers at risk for COPD, who are treated within primary care. OBJECTIVE: The aims of this study were (1) to examine e-visit feasibility and acceptability, particularly as compared to in-lab diagnostic pulmonary function testing (PFT), and (2) to examine the efficacy of smoking cessation e-visits relative to treatment as usual (TAU), all within primary care. METHODS: In a randomized clinical trial, 125 primary care patients who smoke were randomized 2:1 to receive either proactive e-visits or TAU. Participants randomized to the e-visit condition were screened for COPD symptoms via the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE). Those with scores ≥2 were invited to complete both home spirometry and in-lab PFTs, in addition to two smoking cessation e-visits. Smoking cessation e-visits assessed smoking history and motivation to quit and included completion of an algorithm to determine the best Food and Drug Administration-approved cessation medication to prescribe. Primary outcomes included measures related to (1) e-visit acceptability, feasibility, and treatment metrics; (2) smoking cessation outcomes (cessation medication use, 24-hour quit attempts, smoking reduction ≥50%, self-reported abstinence, and biochemically confirmed abstinence); and (3) COPD screening outcomes. RESULTS: Of 85 participants assigned to the e-visits, 64 (75.3%) were invited to complete home spirometry and in-lab PFTs based on CAPTURE. Among those eligible for spirometry, 76.6% (49/64) completed home spirometry, and 35.9% (23/64) completed in-lab PFTs. At 1 month, all cessation outcomes favored the e-visit, with a significant effect for cessation medication use (odds ratio [OR]=3.22). At 3 months, all cessation outcomes except for 24-hour quit attempts favored the e-visit, with significant effects for cessation medication use (OR=3.96) and smoking reduction (OR=3.09). CONCLUSIONS: A proactive, asynchronous e-visit for smoking cessation and COPD screening may offer a feasible, efficacious approach for broad interventions within primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04155073; https://clinicaltrials.gov/ct2/show/NCT04155073.

A Modification of Time-Driven Activity-Based Costing for Comparing Cost of Telehealth and In-Person Visits.

Introduction: Cost studies of telehealth (TH) and virtual visits are few and report mixed results of the economic impact of virtual care and TH. Largely missing from the literature are studies that identify the cost of delivering TH versus in-person care. The objective was to demonstrate a modified time-driven activity-based costing (TDABC) approach to compare weighted labor cost of an in-person pediatric clinic sick visit before COVID-19 to the same virtual and in-person sick-visit during COVID-19. Methods: We examined visits before and during COVID-19 using: (1) recorded structured interviews with providers; (2) iterative workflow mapping; (3) electronic health records time stamps for validation; (4) standard cost weights for wages; and (5) clinic CPT billing code mix for complexity weighs. We examined the variability in estimated time using a decision tree model and Monte Carlo simulations. Results: Workflow charts were created for the clinic before COVID-19 and during COVID-19. Using TDABC and simulations for varying time, the weighted cost of clinic labor for sick visit before COVID-19 was $54.47 versus $51.55 during COVID-19. Discussion: The estimated mean labor cost for care during the pandemic has not changed from the pre-COVID period; however, this lack of a difference is largely because of the increased use of TH. Conclusions: Our TDABC approach is feasible to use under virtual working conditions; requires minimal provider time for execution; and generates detailed cost estimates that have "face validity" with providers and are relevant for economic evaluation.

Preventive Care Utilization by Patients Who Use Virtual Urgent Care.

Introduction: The use of direct to patient (DTP) telemedicine for common acute conditions is widespread. It provides certain advantages over in-person visits, but has led to concerns about fragmentation of care. It is unknown whether use of DTP telemedicine decreases use of primary care services in a way that leads to missed preventive screenings and immunizations. Methods: Virtual urgent care (VUC) is a DTP telemedicine service to treat common acute conditions. All VUC encounters completed at an academic health system from July 2018 to December 2019 were evaluated and analyzed in 2020. Only patients established with primary care (at least one primary care visit in the same year as VUC encounter) were included. Specific preventive screenings (breast cancer, gonorrhea/chlamydia, and cervical cancer) and immunizations (tetanus and influenza) were characterized as up to date based on national guidelines. Chi-squares and multivariate logistic regressions were used to assess receipt of screenings and immunizations. Regressions included VUC and primary care utilization and demographic factors. Results: Patients evaluated (N = 1025) were mostly 25-50 years old (69.7%), women (81.8%), and white (74.9%). More than half (56.5%) had only used VUC once. In multivariate analyses, VUC utilization was not negatively associated with any of the preventive services evaluated, whereas primary care utilization was associated with receipt of both immunizations and gonorrhea/chlamydia screening. Conclusions: Higher VUC utilization is not negatively associated with receipt of preventive services, as long as a primary care relationship is established. VUC may provide a useful method of encouraging receipt of preventive services, especially for younger patients.

Nurse Perspectives Regarding Implementation of an Asthma Monitoring Mobile Health Application in the School Setting.

Background: School-based telehealth (SBTH) plays a valuable role in child asthma management, although nurses have concerns with caregiver engagement. Mobile technology (m-health) has potential to improve this engagement. Objective: We identified barriers and key desired features of an asthma m-health application as a supplement to an existing SBTH asthma program in rural settings. Methods: Multimethod design using school nurse surveys and interviews with school and SBTH personnel to describe processes related to implementation of an m-health application. Results: Nurses reported SBTH programs were an ideal setting to identify potential families for m-health. Benefits of caregiver education and engagement and barriers related to technology, smart phone data availability, and family buy-in were described. Desired application features included education on inhaler technique, asthma symptom, and medication adherence reports. Conclusions: The feedback identified from nurses can be incorporated into an asthma m-health program within an SBTH program to facilitate implementation.

Do Hospitals Providing Telehealth in Emergency Departments Have Lower Emergency Department Costs?

Background: Since 2003, the University of Mississippi Medical Center has operated a robust telehealth emergency department (ED) network, TelEmergency, which enhances access to emergency medicine-trained physicians at participating rural hospitals. TelEmergency was developed as a cost-control measure for financially constrained rural hospitals to improve access to quality, emergency care. However, the literature remains unclear as to whether ED telehealth services can be provided at lower costs compared with traditional in-person ED services. Introduction: Our objective was to empirically determine whether TelEmergency was associated with lower ED costs at rural hospitals when compared with similar hospitals without TelEmergency between 2010 and 2017. Materials and Methods: A panel of data for 2010-2017 was constructed at the hospital level. Hospitals with TelEmergency (n = 14 hospitals; 112 hospital-years) were compared with similar hospitals that did not use TelEmergency from Arkansas, Georgia, Mississippi, and South Carolina (n = 102; 766 hospital-years), matched using Coarsened Exact Matching. The relationship between total ED costs and treatment (e.g., participation in TelEmergency) was predicted using generalized estimating equations with a Poisson distribution, a log link, an exchangeable error term, and robust standard errors. Results: After controlling for ownership type, critical access hospital status, year, and size, TelEmergency was associated with an estimated 31.4% lower total annual ED costs compared with similar matched hospitals that did not provide TelEmergency. Conclusions: TelEmergency utilization was associated with significantly lower total annual ED costs compared with similarly matched hospitals that did not utilize TelEmergency. These findings suggest that access to quality ED care in rural communities can occur at lower costs.

A geographic identifier assignment algorithm with Bayesian variable selection to identify neighborhood factors associated with emergency department visit disparities for asthma.

BACKGROUND: Ecologic health studies often rely on outcomes from health service utilization data that are limited by relatively coarse spatial resolutions and missing geographic information, particularly neighborhood level identifiers. When fine-scale geographic data are missing, the ramifications and strategies for addressing them are not well researched or developed. This study illustrates a novel spatio-temporal framework that combines a geographic identifier assignment (i.e., geographic imputation) algorithm with predictive Bayesian variable selection to identify neighborhood factors associated with disparities in emergency department (ED) visits for asthma. METHODS: ED visit records with missing fine-scale spatial identifiers (~ 20%) were geocoded using information from known, coarser, misaligned spatial units using an innovative geographic identifier assignment algorithm. We then employed systematic variable selection in a spatio-temporal Bayesian hierarchical model (BHM) predictive framework within the NIMBLE package in R. Our novel methodology is illustrated in an ecologic case study aimed at identifying neighborhood-level predictors of asthma ED visits in South Carolina, United States, from 1999 to 2015. The health outcome was annual ED visit counts in small areas (i.e., census tracts) with primary diagnoses of asthma (ICD9 codes 493.XX) among children ages 5 to 19 years. RESULTS: We maintained 96% of ED visit records for this analysis. When the algorithm used areal proportions as probabilities for assignment, which addressed differential missingness of census tract identifiers in rural areas, variable selection consistently identified significant neighborhood-level predictors of asthma ED visit risk including pharmacy proximity, average household size, and carbon monoxide interactions. Contrasted with common solutions of removing geographically incomplete records or scaling up analyses, our methodology identified critical differences in parameters estimated, predictors selected, and inferences. We posit that the differences were attributable to improved data resolution, resulting in greater power and less bias. Importantly, without this methodology, we would have inaccurately identified predictors of risk for asthma ED visits, particularly in rural areas. CONCLUSIONS: Our approach innovatively addressed several issues in ecologic health studies, including missing small-area geographic information, multiple correlated neighborhood covariates, and multiscale unmeasured confounding factors. Our methodology could be widely applied to other small-area studies, useful to a range of researchers throughout the world.

Correction to: A geographic identifier assignment algorithm with Bayesian variable selection to identify neighborhood factors associated with emergency department visit disparities for asthma.

Unfortunately, the original version of the article [1] contained an error. A typo in the main equation (Eq. 1) has been introduced during the production process. The operator " = " in Eq. 1 "log(θik) =  α + ui…" was missing.

Clinical and Technical Considerations of an Open Access Telehealth Network in South Carolina: Definition and Deployment.

BACKGROUND: Today, telehealth is experiencing exponential growth in utilization. Paralleling this trend is the growth in the telehealth industry, with sharp increases in the number of platforms, functionalities, and levels of integrations within both the electronic health record and other technical systems supporting health care. When a telehealth network is intended to be used across independent health care systems, an additional layer of complexity emerges. In the context of regionalized telehealth networks that are not within the same health care system, not only are technical interoperability challenges a practical barrier, but administrative, clinical, and competitive elements also quickly emerge, resulting in fragmented, siloed technologies. OBJECTIVE: The study aimed to describe a statewide approach to deploying an interoperable open access telehealth network across multiple health systems. METHODS: One promising solution to the abovementioned concerns is an open access telehealth network. In the field of telehealth, an open access network (OAN) can be defined as a network infrastructure that can be used by health care providers without a closed or proprietary platform, specific obligatory network, or service-specific telehealth technologies. This framework for the development of an OAN is grounded in practical examples of clinical programs that function in each stage of network maturity based on the experience of the South Carolina Telehealth Alliance (SCTA). The SCTA's experience details successes and challenges in an ongoing effort to achieve an OAN. The model describes an OAN in stages of collaborative maturity and provides insights into the technological, clinical, and administrative implications of making the collaboration possible. RESULTS: The four stages of an OAN are defined according to operational maturity, ranging from feasibility to demonstration of implementation. Each stage is associated with infrastructure and resource requirements and technical and clinical activities. In stage 1, technical standards are agreed upon, and the clinical programs are designed to utilize compliant technologies. In stage 2, collaboration is demonstrated through technical teams working together to address barriers, whereas clinical and administrative teams share best practices. In stage 3, a functional interoperable network is demonstrated with different institutions providing service through common telehealth end points at different patient care sites. In stage 4, clinical workflows are streamlined and standardized across institutions, and economies of scale are achieved through technical and administrative innovations. CONCLUSIONS: The approach to OAN development described provides a roadmap for achieving a functional telehealth network across independent health systems. The South Carolina experience reveals both successes and challenges in achieving this goal. The next steps toward the development of OANs include advocacy and ongoing engagement with the developers of telehealth technologies regarding their commitment to interoperability.

Intersection of the p63 and NF-κB pathways in epithelial homeostasis and disease.

Overexpression of ΔNp63α, a member of the p53/p63/p73 family of transcription factors, is a molecular attribute of human squamous cancers of the head and neck, lung and skin. The TP63 gene plays important roles in epidermal morphogenesis and homeostasis, regulating diverse biological processes including epidermal fate decisions and keratinocyte proliferation and survival. When overexpressed experimentally in primary mouse keratinocytes, ΔNp63α maintains a basal cell phenotype including the loss of normal calcium-mediated growth arrest, at least in part through the activation and enhanced nuclear accumulation of the c-rel subunit of NF-κB (Nuclear Factor-kappa B). Initially identified for its role in the immune system and hematopoietic cancers, c-Rel has increasingly been associated with solid tumors and other pathologies. ΔNp63α and c-Rel have been shown to be associated in the nuclei of ΔNp63α overexpressing human squamous carcinoma cells. Together, these transcription factors cooperate in the transcription of genes regulating intrinsic keratinocyte functions, as well as the elaboration of factors that influence the tumor microenvironment (TME). This review provides an overview of the roles of ΔNp63α and c-Rel in normal epidermal homeostasis and elaborates on how these pathways may intersect in pathological conditions such as cancer and the associated TME.

Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis.

The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.

Perceptions of Adolescent Patients of the "Lived Experience" of Type 1 Diabetes.

The care and management of adolescents with type 1 diabetes presents numerous challenges that are inherent to the fears, attitudes, and perceptions of their illness. This qualitative study aimed to explore the "lived experience" of individuals with type 1 diabetes. In-depth interviews were conducted with 20 patients diagnosed with type 1 diabetes in their adolescent years to elicit their views, perceptions, and concerns regarding living with diabetes. All interviews were conducted and analyzed using the principles of grounded theory. Five categories defining the patients' lived experience were elicited: Barriers, Develop Skills, Manage Emotion, Social World, and Health Care Professionals. The problems experienced by adolescents with type 1 diabetes are multifactorial. Existentially, type 1 diabetes affects their daily activities and impinges on their academic achievement and personal aspirations. They have great difficulty coping with their health status and highlight a lack of empathy from health care professionals (HCPs). Their major fear is of hypoglycemia, resulting in their subsequent focus of preventing hypoglycemic episodes. Indeed, regardless of consequence, blood glucose levels are often deliberately kept above recommended levels, which serves to decrease the effectiveness of their health care management. This study shows that the quality of care provided for adolescent patients with type 1 diabetes is failing to meet their expectations and falls short of the essential standards commensurate with current health care policy. Improvements in long-term care management for these patients require changes in both patients' and professionals' understanding of the disease and of the ways it is managed.