Off the hamster wheel? Qualitative evaluation of a payment-linked patient-centered medical home (PCMH) pilot.

CONTEXT: Many primary care practices are moving toward the patient-centered medical home (PCMH) model and increasingly are offering payment incentives linked to PCMH changes. Despite widespread acceptance of general PCMH concepts, there is still a pressing need to examine carefully and critically what transformation means for primary care practices and their patients and the experience of undergoing such change in a practice. METHODS: We used a qualitative case study approach to explore the underlying dynamics of change at five practices participating in PCMH transformation efforts linked to payment reform. The evaluation consisted of structured site visits, interviews, observations, and artifact reviews followed by a structured review of transcripts and documents for patterns, themes, and insights related to PCMH implementation. FINDINGS: We describe both the detailed components of each practice's transformation efforts and a grounded taxonomy of eight insights stemming from the experiences of these medical homes. We identified specific contextual factors related to wide variations in change tactics. We also observed widely varying approaches to catalyzing change using (or not) external consultants, specific challenges regarding health information technology implementation, team and staff role restructuring, compensation, and change fatigue, and several unexpected potential confounders or alternative explanations for practice success. CONCLUSIONS: Our evaluation affirms the value and necessity of qualitative methods for understanding primary care practice transformation, and it should encourage ongoing and future pilots to include assessments of the PCMH change process beyond clinical markers and claims data. The results raise insights into the heterogeneity of medical home transformation, the central but complex role of payment reform in creating a space for change, the ability of small practices to achieve substantial change in a short time period, and the challenges of sustaining it.

Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.

The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert(+) cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.

Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells.

Stem cells hold great promise for regenerative medicine, but remain elusive in many tissues in part because universal markers of "stemness" have not been identified. The ribonucleoprotein complex telomerase catalyzes the extension of chromosome ends, and its expression is associated with failure of cells to undergo cellular senescence. Because such resistance to senescence is a common characteristic of many stem cells, we hypothesized that telomerase expression may provide a selective biomarker for stem cells in multiple tissues. In fact, telomerase expression has been demonstrated within hematopoietic stem cells. We therefore generated mouse telomerase reverse transcriptase (mTert)-GFP-transgenic mice and assayed the ability of mTert-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine. mTert-GFP mice were generated by using a two-step embryonic stem cell-based strategy, which enabled primary and secondary screening of stably transfected clones before blastocyst injection, greatly increasing the probability of obtaining mTert reporter mice with physiologically appropriate regulation of GFP expression. Analysis of adult mice showed that GFP is expressed in differentiating male germ cells, is enriched among BM-derived hematopoietic stem cells, and specifically marks long-term BrdU-retaining intestinal crypt cells. In addition, telomerase-expressing GFP(+) BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence that mTert-GFP expression marks progenitor cells in blood and small intestine, validating these mice as a useful tool for the prospective identification, isolation, and functional characterization of progenitor/stem cells from multiple tissues.