The Role of Information and Nudges on Advance Directives and End-of-Life Planning: Evidence From a Randomized Trial.

Despite the substantial personal and economic implications of end-of-life decisions, many individuals fail to document their wishes, which often leads to patient dissatisfaction and unnecessary medical spending. We conducted a randomized trial of 1,200 patients aged 55 years and older to facilitate advance directive (AD) completion and better understand why patients fail to engage in high-value planning. We found that including a physical AD form with paper letters as a nudge to decrease hassle costs increased AD completion by 9.0 percentage points (95% confidence interval [CI] = [4.2, 13.9] percentage points). The intervention was especially effective for individuals aged 70 years and older, as AD completion increased by 17.5 percentage points (95% CI = [5.7, 9.4] percentage points). When compared with the impact of costless electronic reminders, each additional AD completion from the letter interventions costs as little as US$37. Our findings suggest that simple, inexpensive interventions with paper communication as behavioral nudges can be effective, especially in older populations.

Inhibition of a signaling modality within the gp130 receptor enhances tissue regeneration and mitigates osteoarthritis.

Adult mammals are incapable of multitissue regeneration, and augmentation of this potential may shift current therapeutic paradigms. We found that a common co-receptor of interleukin 6 (IL-6) cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) were resistant to surgically induced osteoarthritis as reflected by reduced loss of proteoglycans, reduced synovitis, and synovial fibrosis. The F814 mice also exhibited enhanced regenerative, not reparative, responses after wounding in the skin. In addition, pharmacological modulation of gp130 Y814 upstream of the SRC and MAPK circuit by a small molecule, R805, elicited a protective effect on tissues after injury. Topical administration of R805 on mouse skin wounds resulted in enhanced hair follicle neogenesis and dermal regeneration. Intra-articular administration of R805 to rats after medial meniscal tear and to canines after arthroscopic meniscal release markedly mitigated the appearance of osteoarthritis. Single-cell sequencing data demonstrated that genetic and pharmacological modulation of Y814 resulted in attenuation of inflammatory gene signature as visualized by the anti-inflammatory macrophage and nonpathological fibroblast subpopulations in the skin and joint tissue after injury. Together, our study characterized a molecular mechanism that, if manipulated, enhances the intrinsic regenerative capacity of tissues through suppression of a proinflammatory milieu and prevents pathological outcomes in injury and disease.

The Health Plan Environment In California Contributed To Differential Use Of Telehealth During The COVID-19 Pandemic.

The COVID-19 pandemic has led to substantial increases in the use of telehealth and virtual care in the US. Differential patient and provider access to technology and resources has raised concerns that existing health disparities may be extenuated by shifts to virtual care. We used data from one of the largest providers of employer-sponsored insurance, the California Public Employees' Retirement System, to examine potential disparities in the use of telehealth. We found that lower-income, non-White, and non-English-speaking people were more likely to use telehealth during the period we studied. These differences were driven by enrollment in a clinically and financially integrated care delivery system, Kaiser Permanente. Kaiser's use of telehealth was higher before and during the pandemic than that of other delivery models. Access to integrated care may be more important to the adoption of health technology than patient-level differences.

Health Insurance for "Humans": Information Frictions, Plan Choice, and Consumer Welfare.

Traditional models of insurance choice are predicated on fully informed and rational consumers protecting themselves from exposure to financial risk. In practice, choosing an insurance plan is a complicated decision often made without full information. In this paper we combine new administrative data on health plan choices and claims with unique survey data on consumer information to identify risk preferences, information frictions, and hassle costs. Our additional friction measures are important predictors of choices and meaningfully impact risk preference estimates. We study the implications of counterfactual insurance allocations to illustrate the importance of distinguishing between these micro-foundations for welfare analysis.

Adverse Selection and Inertia in Health Insurance Markets: When Nudging Hurts.

This paper investigates consumer inertia in health insurance markets, where adverse selection is a potential concern. We leverage a major change to insurance provision that occurred at a large firm to identify substantial inertia, and develop and estimate a choice model that also quantifies risk preferences and ex ante health risk. We use these estimates to study the impact of policies that nudge consumers toward better decisions by reducing inertia. When aggregated, these improved individual-level choices substantially exacerbate adverse selection in our setting, leading to an overall reduction in welfare that doubles the existing welfare loss from adverse selection.

Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by coculture with human fetal gonadal cells.

The derivation of germ cells from human embryonic stem cells (hESCs) or human induced pluripotent stem (hIPS) cells represents a desirable experimental model and potential strategy for treating infertility. In the current study, we developed a triple biomarker assay for identifying and isolating human primordial germ cells (PGCs) by first evaluating human PGC formation during the first trimester in vivo. Next, we applied this technology to characterizing in vitro derived PGCs (iPGCs) from pluripotent cells. Our results show that codifferentiation of hESCs on human fetal gonadal stromal cells significantly improves the efficiency of generating iPGCs. Furthermore, the efficiency was comparable between various pluripotent cell lines regardless of origin from the inner cell mass of human blastocysts (hESCs), or reprogramming of human skin fibroblasts (hIPS). To better characterize the iPGCs, we performed Real-time polymerase chain reaction, microarray, and bisulfite sequencing. Our results show that iPGCs at day 7 of differentiation are transcriptionally distinct from the somatic cells, expressing genes associated with pluripotency and germ cell development while repressing genes associated with somatic differentiation (specifically multiple HOX genes). Using bisulfite sequencing, we show that iPGCs initiate imprint erasure from differentially methylated imprinted regions by day 7 of differentiation. However, iPGCs derived from hIPS cells do not initiate imprint erasure as efficiently. In conclusion, our results indicate that triple positive iPGCs derived from pluripotent cells differentiated on hFGS cells correspond to committed first trimester germ cells (before 9 weeks) that have initiated the process of imprint erasure.