Women's Health Provider Perspectives on Reproductive Services Provision in the Veterans Health Administration.

OBJECTIVES: Women veterans are a fast-growing population in the Veterans Health Administration (VHA), and ensuring reproductive service availability is a VHA priority. As such, we sought to explore barriers and facilitators to VHA reproductive service provision across a catchment area from women's health providers' perspectives. METHODS: We performed a mixed-methods study, including semistructured, qualitative provider interviews with a quantitative survey on training, comfort, and knowledge of reproductive services. All women's health providers and their support staff from the Salt Lake City Veterans Affairs Medical Center and nine VHA community-based outpatient clinics were asked to participate. We conducted qualitative interviews and knowledge surveys with providers and staff to explore training, care processes, and improvement opportunities in reproductive service provision. We completed descriptive analyses of all of the quantitative data and used an open, iterative process to analyze provider interviews for emergent themes. RESULTS: We interviewed 15 providers (7 advanced practice nurses, 4 registered nurses, and 4 physicians) across nine sites (50% response rate). The commonly identified barriers included provider training and staffing, scheduling/referral processes, inconsistent services/supplies, and lack of veteran awareness of reproductive services. Facilitators included prior non-VHA reproductive health experience among providers, invested support staff, and the integrated VHA health system. CONCLUSIONS: Addressing barriers to VHA reproductive healthcare provision may overcome reproductive service variations related to clinic location and improve reproductive health outcomes for women veterans.

Supporting families during pediatric critical illness: Opportunities identified in a multicenter, qualitative study.

Critical illness resulting in a pediatric intensive care unit (PICU) admission is a profoundly stressful experience for a child and their family. Increasing evidence for emotional and behavioral sequelae post-PICU emphasizes a need to provide better support for families throughout this period of care and recovery. The aim of this qualitative investigation was to identify salient and modifiable aspects of a critical care experience that can be addressed to better support families of critically ill children. Individual semi-structured interviews were conducted with 26 caregivers of children who survived a PICU admission. Interviews were audio-recorded and transcribed verbatim; themes were identified via thematic analysis. Caregivers were enrolled using convenience sampling from seven tertiary care PICUs in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Themes from caregiver interviews were identified within two overarching categories containing three themes each. Advice for future PICU families: (1) Be intentional about caring for your own well-being, (2) speak up, ask questions, and challenge decisions you're not comfortable with, and (3) continue to engage with your child. Characteristics of a satisfactory PICU experience: (1) A caregiver-provider relationship of mutual trust established through clear communication and respectful collaboration, (2) hospital environments that provide physical and social supports to maintain humanity in healthcare, and (3) preparing families for care transitions. Targeted, interdisciplinary approaches to partner with families during critical care may improve their PICU experience and contribute to improved long-term outcomes for PICU survivors.

Pioneering models of pediatric brain tumors.

Among children and adolescents in the United States (0 to 19 years old), brain and other central nervous system tumors are the second most common types of cancers, surpassed in incidence only by leukemias. Despite significant progress in the diagnosis and treatment modalities, brain cancer remains the leading cause of death in the pediatric population. There is an obvious unfulfilled need to streamline the therapeutic strategies and improve survival for these patients. For that purpose, preclinical models play a pivotal role. Numerous models are currently used in pediatric brain tumor research, including genetically engineered mouse models, patient-derived xenografts and cell lines, and newer models that utilize novel technologies such as genome engineering and organoids. Furthermore, extensive studies by the Children's Brain Tumor Network (CBTN) researchers and others have revealed multiomic landscapes of variable pediatric brain tumors. Combined with such integrative data, these novel technologies have enabled numerous applicable models. Genome engineering, including CRISPR/Cas9, expanded the flexibility of modeling. Models generated through genome engineering enabled studying particular genetic alterations in clean isogenic backgrounds, facilitating the dissection of functional mechanisms of those mutations in tumor biology. Organoids have been applied to study tumor-to-tumor-microenvironment interactions and to address developmental aspects of tumorigenesis, which is essential in some pediatric brain tumors. Other modalities, such as humanized mouse models, could potentially be applied to pediatric brain tumors. In addition to current valuable models, such novel models are anticipated to expedite functional tumor biology study and establish effective therapeutics for pediatric brain tumors.

Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity.

Cyclic nucleotide phosphodiesterase-8 (PDE8) is a family of cAMP-specific enzymes and plays important roles in many biological processes, including T-cell activation, testosterone production, adrenocortical hyperplasia, and thyroid function. However, no PDE8 selective inhibitors are available for trial treatment of human diseases. Here we report kinetic properties of the highly active PDE8A1 catalytic domain prepared from refolding and its crystal structures in the unliganded and 3-isobutyl-1-methylxanthine (IBMX) bound forms at 1.9 and 2.1 A resolutions, respectively. The PDE8A1 catalytic domain has a K(M) of 1.8 microM, V(max) of 6.1 micromol/min/mg, a k(cat) of 4.0 s(-1) for cAMP, and a K(M) of 1.6 mM, V(max) of 2.5 micromol/min/mg, a k(cat) of 1.6 s(-1) for cGMP, thus indicating that the substrate specificity of PDE8 is dominated by K(M). The structure of the PDE8A1 catalytic domain has similar topology as those of other PDE families but contains two extra helices around Asn685-Thr710. Since this fragment is distant from the active site of the enzyme, its impact on the catalysis is unclear. The PDE8A1 catalytic domain is insensitive to the IBMX inhibition (IC(50) = 700 microM). The unfavorable interaction of IBMX in the PDE8A1-IBMX structure suggests an important role of Tyr748 in the inhibitor binding. Indeed, the mutation of Tyr748 to phenylalanine increases the PDE8A1 sensitivity to several nonselective or family selective PDE inhibitors. Thus, the structural and mutagenesis studies provide not only insight into the enzymatic properties but also guidelines for design of PDE8 selective inhibitors.

Transportation barriers to accessing health care for urban children.

The Texas Children's Hospital Residents' Primary Care Group Clinic provides primary care to urban low-income children. The objective of this cross-sectional study was to investigate the impact of transportation problems on a family's ability to keep an appointment. One hundred eighty-three caregivers of children with an appointment were interviewed. Caregivers who kept their appointment were compared with those who did not with respect to demographic and transportation-related characteristics. Logistic regression modeling predicted caregivers with the following characteristics were more likely not to keep an appointment: not using a car to the last kept appointment, not keeping an appointment in the past due to transportation problems, having more than two people in the household, and not keeping an appointment in the past due to reasons other than transportation problems. Future research should focus on developing interventions to help low-income urban families overcome non-financial access barriers, including transportation problems.