Recent work indicates that the growth and behavior of cancers are ultimately determined by a small subpopulation of malignant stem cells and that information about the properties of these cells is urgently needed to enable their targeting for therapeutic elimination. A key feature of normal stem cells is their asymmetrical division, the mechanism that allows stem cell self-renewal while producing hierarchies of amplifying and differentiating cells that form the bulk of the tissue. Most cancer deaths result from epithelial malignancies, but the extent to which the hierarchical proliferative stem and amplifying cell patterns of normal epithelia are actually retained in epithelial malignancies has been unclear. Here we show that even cell lines generated from carcinomas consistently produce in vitro colony patterns unexpectedly similar to those produced by the stem and amplifying cells of normal epithelia. From the differing types of colony morphologies formed, it is possible to predict both the growth potential of their constituent cells and their patterns of macromolecular expression. Maintenance of a subpopulation of stem cells during passage of cell lines indicates that the key stem cell property of asymmetrical division persists but is shifted towards enhanced stem cell self-renewal. The presence of malignant epithelial stem cells in vivo has been shown by serial transplantation of primary cancer cells and the present observations indicate that stem cell patterns are robust and persist even in cell lines. An understanding of this behavior should facilitate studies directed towards the molecular or pharmacologic manipulation of malignant stem cell survival.

There is a well-known subgroup of children and adolescents with complex medical conditions who have many psychosocial challenges that put them at risk for repeated and, at times, avoidable hospitalizations. Intensive behavioral health interventions that address the multitude of problems associated with complex medical conditions have proven effective in improving adherence to treatment, improving overall psychosocial functioning, and reducing avoidable hospitalizations. Based largely on this research, we adapted and augmented a family-based problem-solving intervention for youth with complex medical conditions who have been repeatedly hospitalized. The intervention involves intensive family based problem solving augmented with care coordination and case management. The intervention is implemented in the family’s home, in the hospital, in the clinic, over e-mail, via video teleconferencing, and by text. To our knowledge, this effort is a first in the application of intensive behavioral health care for youth with complex medical conditions who are repeatedly hospitalized. We describe the theoretical and empirical underpinnings of the intervention, provide a description of the intervention using a case example, and present “lessons learned” from our efforts toward reducing hospitalizations and utilization of services in a population of youth with complex medical conditions who have repeatedly experienced avoidable hospitalizations.

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The purpose of this study was to pilot the implementation of the Novel Interventions in Children’s Healthcare (NICH) program for youth with chronic pain who utilized a disproportionate amount of health care. Three youth (2 males and 1 female, aged 11 to 15 years) participated. The intervention consisted of a combination of family-based problem-solving, care coordination, and case management, with the inclusion of technology-assisted treatment delivery (e.g., text messages, video chat) to reduce costs. Both objective (i.e., hospitalization records) and subjective (e.g., interventionist reports) outcomes were examined to assess changes over the course of treatment. Two of the three youth demonstrated reductions in the number of days hospitalized and associated costs. In addition, interventionist reports indicated improved quality of life for family and youth served. Although further research is needed, NICH appears to be a promising intervention for youth with chronic pain and high health care utilization and shows the potential to result in improved youth health and reduced monetary costs for families, providers, and the healthcare system.

Objective: Novel Interventions in Children’s Healthcare (NICH), an intensive behavioral health program, has demonstrated promise in reducing avoidable complications in youth with T1D. However, it is unclear whether these outcomes are consistent across regions, and how those variables may impact intensity of service delivery. This study aims to identify whether region and distance from NICH team base, when considering treatment intensity, moderate NICH outcomes. Methods: Youth with T1D served by NICH and covered by one of four major Medicaid providers were included (n=47). EHR review included frequency of DKA one year prior and two years following initiation of NICH services, distance from NICH team, type of region, and intensity of services delivered. Results: NICH youth demonstrated similar DKA reduction regardless of living in a rural or urban community. NICH providers delivered a per-family mean of 3 hours and 58 minutes per week of indirect and direct services, with more time spent in face-to-face service delivery and less time on transportation with families living closer to NICH team. NICH providers were significantly (p<.05) more likely to meet weekly with caregivers if youth lived within an hour of the team. When examining DKA incidence following NICH initiation, youth living more than one hour from the NICH team averaged a 46% decrease, those within 1-2 hours showed a 71% decrease, and those living more than 2 hours away showed no change in DKA frequency. Conclusion: This study represents the first examination of how system-level characteristics might moderate NICH services and related effectiveness. While outcomes were similar across urban and rural communities, NICH youth living closer to the NICH team experienced greater caregiver access to services and were more likely to demonstrate reductions in DKAs compared to those living more than 2 hours away. Such findings have implications for model adaptation and dissemination. Disclosure C. Jenisch: None. D.V. Wagner: None. A.F. Manabat: None. M. Heywood: None. E. Karkula: None. A. Sheffield: None. J.D. Ogden: None. H. Nagra: None. M.A. Harris: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust