Search

Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms. In this study, we describe the prevalence, pharmacologic treatment, and control of hypertension over time among older adults residing in Veterans Affairs (VA) nursing homes from October 2006 through September 2018 (FY2007-2018). Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long-term care residents aged 65 years and older. Hypertension prevalence at admission was identified by one or more ICD code(s) in the year prior, and antihypertensive medication use was considered present if administered ≥50% of days in the nursing home. BP measures were obtained from the electronic health record and averaged over 2 year epochs. The age-standardized prevalence of hypertension diagnosis at admission increased over time from 75.2% in FY2007-2008 to 85.1% in FY2017-2018 (p-value for trend 140/90 mmHg. Future research is needed to better understand the ratio of benefits to harms of BP control in nursing home residents.

The progress made in directed differentiation of stem cells has shown that understanding human pancreas development can provide cues for generating unlimited amounts of insulin-producing beta cells for transplantation therapy in diabetes. However, current differentiation protocols have not been successful in reproducibly generating functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single cell RNA sequencing with spatial transcriptomics at multiple developmental timepoints and revealed distinct temporal-spatial gene cascades in the developing human pancreas. Cell trajectory inference identified endocrine progenitor populations and novel branch-specific genes as the progenitors differentiate towards alpha or beta cells, indicating that transcriptional maturation occurred over this developmental timeframe. Spatial differentiation trajectories indicated that immature Schwann cells are spatially co-located with endocrine progenitors and contribute to beta cell maturation via the L1CAM-EPHB2 pathway. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for interrogating human pancreas development for the research community.

Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.

Blood pressure (BP) is a complex dynamic system in the human body and an important determinant of healthy aging. Exploring BP as a dynamic data system may provide important insights into how BP patterns can provide complementary information to the static, one-time BP measurements that are more commonly used for clinical decision making. Thus, we sought to describe BP as a dynamic data system in older adults nearing death. Using a prospective cohort study design, we assessed BP measures 6 months before death in Veterans Health Administrative nursing home residents between 10/1/2006 and 9/30/2017. Variability was characterized using standard deviation and mean square error after adjusting for diurnal variations. Complexity (i.e., amount of novel information vs. redundancy) was examined using Shannon’s entropy (bits). Generalized linear models were used to examine factors associated with overall BP variability. We identified 17,953 patients (98.0% male, 82.5% White, mean age 80.2 years, and mean BP 125.7/68.6 mmHg). In the last 6 months of life, systolic BP decreased slightly (□-7.2mmHg). Variability was stable until the last month of life, at which point variability increased by as much as 30%. In contrast, complexity did not change in the 6 months before death (□0.02 bits). Factors associated with BP variability before death include hospitalizations, hospice care, and medication changes. Systolic BP decreases in the last 6 months before death, and BP variability increases in the last month of life. Further, the increase in BP variability may be driven by increasingly complex care patterns as one approaches death.