Does missing trust lead to overuse or underuse of health care services?

Research about mistrust in health care often relies on the narrative that lacking trust causes underuse of health care services. This narrative seemed to hold up in the COVID-19 pandemic era, when mistrust in systems and providers led to widely recognized vaccine hesitancy and reluctance to seek care. In this review, we suggest that the "mistrust leads to underuse" narrative is important but incomplete, as mistrust in health care may also cause patients to overuse health care services. We searched the literature for studies, meta-analyses, and interviews that assessed the effect of patient trust on health care utilization. Although overuse literature is sparse, surveys and physician interviews indicate that patients who do not trust their clinicians may seek multiple opinions on the same diagnosis and utilize more costly interventions that are not recommended. Physicians also report being more likely to utilize extraneous tests and medications when patients do not trust them. Hence, problems of trust may lead to both underuse and overuse of health care services. We postulate several factors that may influence whether a mistrustful patient underuses or overuses health care resources, including personal characteristics, environmental characteristics, and levels of analysis, and we encourage more investigation about mistrust and health care overutilization.

Multi-ancestral origin of intestinal tumors: Impact on growth, progression, and drug efficacy.

BACKGROUND: Data are steadily accruing that demonstrate that intestinal tumors are frequently derived from multiple founding cells, resulting in tumors comprised of distinct ancestral clones that might cooperate or alternatively compete, thereby potentially impacting different phases of the disease process. AIM: We sought to determine whether tumors with a multi-ancestral architecture involving at least two distinct clones show increased tumor number, growth, progression, or resistance to drug intervention. METHODS: Mice carrying the Min allele of Apc were generated that were mosaic with only a subset of cells in the intestinal epithelium expressing an activated form of PI3K, a key regulatory kinase affecting several important cellular processes. These cells were identifiable as they fluoresced green, whereas all other cells fluoresced red. RESULTS: Cell lineage tracing revealed that many intestinal tumors from our mouse model were derived from at least two founding cells, those expressing the activated PI3K (green) and those which did not (red). Heterotypic tumors with a multi-ancestral architecture as evidenced by a mixture of green and red cells exhibited increased tumor growth and invasiveness. Clonal architecture also had an impact on tumor response to low-dose aspirin. Aspirin treatment resulted in a greater reduction of heterotypic tumors derived from multiple founding cells as compared to tumors derived from a single founding cell. CONCLUSION: These data indicate that genetically distinct tumor-founding cells can contribute to early intratumoral heterogeneity. The coevolution of the founding cells and their progeny enhances colon tumor progression and impacts the response to aspirin. These findings are important to a more complete understanding of tumorigenesis with consequences for several distinct models of tumor evolution. They also have practical implications to the clinic. Mouse models with heterogenous tumors are likely better for predicting drug efficacy as compared to models in which the tumors are highly homogeneous. Moreover, understanding how interactions among different populations in a single heterotypic tumor with a multi-ancestral architecture impact response to a single agent and combination therapies are necessary to fully develop personalized medicine.