Effects of mRNA conformational switching on translational noise in gene circuits.

Intragenic translational heterogeneity describes the variation in translation at the level of transcripts for an individual gene. A factor that contributes to this source of variation is the mRNA structure. Both the composition of the thermodynamic ensemble, i.e., the stationary distribution of mRNA structures, and the switching dynamics between those play a role. The effect of the switching dynamics on intragenic translational heterogeneity remains poorly understood. We present a stochastic translation model that accounts for mRNA structure switching and is derived from a Markov model via approximate stochastic filtering. We assess the approximation on various timescales and provide a method to quantify how mRNA structure dynamics contributes to translational heterogeneity. With our approach, we allow quantitative information on mRNA switching from biophysical experiments or coarse-grain molecular dynamics simulations of mRNA structures to be included in gene regulatory chemical reaction network models without an increase in the number of species. Thereby, our model bridges a gap between mRNA structure kinetics and gene expression models, which we hope will further improve our understanding of gene regulatory networks and facilitate genetic circuit design.

Cost Reduction and Utilization Patterns in a Medicare Accountable Care Organization Using Home-Based Palliative Care Services.

Accountable care organizations (ACOs) are often tasked with helping providers to deliver care efficiently and with higher quality outcomes. For an ACO to succeed in delivering efficient care, it is important to direct resources toward patients who exhibit the greatest levels of opportunity while focusing attention toward mitigating their needs. Home-based palliative care (HBPC) services are known to address patient needs for those with serious illness while decreasing the total cost of care (TCC). In this retrospective review, ACO researchers reviewed cost, quality, and utilization patterns for 3418 beneficiaries within a Medicare Shared Saving Program approaching the end of life comparing decedents who received HBPC versus those who did not receive the service. Those individuals who received HBPC services were significantly less likely to be hospitalized (51% reduction in the HBPC group), more likely to use hospice (70% vs. 43%; P = 0.001), and their TCC was less than that of those who did not receive the service ($27,203 vs. $36,089: P = 0.0163). Although more research needs to be done to understand the specific components of care delivery that are helpful in decreasing unnecessary utilization, in this retrospective review in an accountable care population, HBPC is associated with a significant decrease in cost and utilization in a population approaching end of life.

Bye bye, linearity, bye: quantification of the mean for linear CRNs in a random environment.

Molecular reactions within a cell are inherently stochastic, and cells often differ in morphological properties or interact with a heterogeneous environment. Consequently, cell populations exhibit heterogeneity both due to these intrinsic and extrinsic causes. Although state-of-the-art studies that focus on dissecting this heterogeneity use single-cell measurements, the bulk data that shows only the mean expression levels is still in routine use. The fingerprint of the heterogeneity is present also in bulk data, despite being hidden from direct measurement. In particular, this heterogeneity can affect the mean expression levels via bimolecular interactions with low-abundant environment species. We make this statement rigorous for the class of linear reaction systems that are embedded in a discrete state Markov environment. The analytic expression that we provide for the stationary mean depends on the reaction rate constants of the linear subsystem, as well as the generator and stationary distribution of the Markov environment. We demonstrate the effect of the environment on the stationary mean. Namely, we show how the heterogeneous case deviates from the quasi-steady state (Q.SS) case when the embedded system is fast compared to the environment.

Association Between Outpatient Rehabilitation Therapy and Total Cost of Care for a Frail Elderly Population in a Medicare Accountable Care Organization.

Frailty is a debilitating and increasingly costly condition in an elderly population equating to nearly $7.6 billion in Medicare spending in 2016. Understanding the burden of frailty and how to manage this population efficiently is of key importance in an accountable care organization. Using an operational, claims-derived definition of frailty, the authors set out to explore the association between therapy and total cost of care for the frail elderly population. Claims data were reviewed for nearly 94,000 beneficiaries to identify the burden of frailty in that population along with the association with therapy utilization. Nearly 10% of patients in the study populations were found to meet the operational definition of frailty. When the frail population is segmented into those who receive outpatient rehabilitation therapy and those who do not, outpatient rehabilitation therapy is associated with decreased cost at 13-32 therapy units delivered. Outside of this dose range, outpatient rehabilitation therapy was not associated with statistically significant improvements in total cost of care for this population. Results suggest that from the standpoint of population health management, utilization of outpatient rehabilitation services may be helpful to decrease costs in several domains. When that cost reduction is compared to therapy units delivered, it is demonstrated that outpatient rehabilitation therapy is associated with lower costs at a certain quantity of therapy. This study has implications for population health management of a frail elderly cohort as well as for managing preferred partnerships with therapy providers, given the wide array of therapy patterns delivered.

We Know Health Is Not Elective: Impacts of COVID-19.

Several months into the impact of the global COVID-19 pandemic, the authors use the framework of "radical uncertainty" and specific regional health care data to understand current and future health and economic impacts. Four key areas of discussion included are: (1) How did structural health care inequality manifest itself during the closure of all elective surgeries and visits?; (2) How can we really calculate the so-called untold burden that resulted from the closure, with a special emphasis on primary care?; (3) The Pennsylvania experience - using observations from the population of one major delivery ecosystem (Jefferson Health), a major accountable care organization (Delaware Valley ACO), and statewide data from Pennsylvania; and (4) What should be the priorities and focus of the delivery system of the future given the dramatic financial and clinical disruption of COVID-19?

The Association of Increasing Hospice Use With Decreasing Hospital Mortality: An Analysis of the National Inpatient Sample.

EXECUTIVE SUMMARY: Usage of hospice services for patients facing life-limiting illness has steadily increased. In these services, hospitals discharge patients to various hospice settings, including the inpatient model, where a patient may remain in the discharging hospital to receive hospice services. In this discharge practice, the patient is considered a hospital survivor and subsequent hospice death. The purpose of the study was to determine if the decline of in-hospital mortality for six common high-volume admission diagnoses could be attributed in part to an increase in discharges to a hospice setting for end-of-life care. In this retrospective study using the National Inpatient Sample database from 2007 to 2011, we identified patients ≥18 years for six acute and chronic diagnoses: heart failure, chronic obstructive pulmonary disease, acute myocardial infarction, acute myocardial infarction with cardiogenic shock, septic shock, and lung neoplasm (cancer). We categorized patients according to their hospital discharge disposition as hospice or in-hospital mortality. A total of 10,458,728 patients met our criteria, of which 2.72% were discharged to hospice and 6.38% died. Compared to patients who died in the hospital, hospice patients were older, had a shorter length of stay, and experienced more comorbidities. Hospice use was more common in Medicare patients, in nonteaching hospitals, and in the South. White individuals were more likely to be discharged to hospice compared to nonwhites. Among the six selected diagnoses over the 5-year period, hospice use rose as observed mortality decreased. Our findings suggest that variability among hospitals in hospice use will affect benchmarked hospital mortality comparisons and could inappropriately reward or penalize hospitals in their public reporting.

The Efficacy of Medical Marijuana in the Treatment of Cancer-Related Pain.

Background: The opioid epidemic has spurred investigations for nonopioid options, yet limited research persists on medical marijuana's (MMJ) efficacy in managing cancer-related symptoms. Objective: We sought to characterize MMJ's role on symptomatic relief and opioid consumption in the oncologic population. Design: Retrospective chart review of MMJ-certified oncology patients was performed. Divided patients into MMJ use [MMJ(+)] versus no use [MMJ(-)], and Edmonton Symptom Assessment System (ESAS)-reported pain cohorts: "mild-moderate" versus "severe." Measurements: Medical records were reviewed for ESAS, to measure physical and emotional symptoms, and opiate consumption, converted into morphine milligram equivalents (MME). Minimal clinically important differences were determined. Wilcoxon signed-rank tests determined statistical significance between MMJ-certification and most recent palliative care visit. Results: Identified 232 patients [95/232 MMJ(-); 137/232 MMJ(+)]. Pain, physical and total ESAS significantly improved for total MMJ(-) and MMJ(+); however, only MMJ(+) significantly improved emotional ESAS. MMJ(-) opioid consumption increased by 23% (97.5-120 mg/day MME, p = 0.004), while it remained constant (45-45 mg/day MME, p = 0.522) in MMJ(+). Physical and total ESAS improved in mild-moderate-MMJ(-) and MMJ(+). Pain and emotional symptoms worsened in MMJ(-); while MMJ(+)'s pain remained unchanged and emotional symptoms improved. MMJ(-) opioid consumption increased by 29% (90-126 mg/day MME, p = 0.012); while MMJ(+)'s decreased by 33% (45-30 mg/day MME, p = 0.935). Pain, physical, emotional, and total ESAS scores improved in severe-MMJ(-) and MMJ(+); opioid consumption reduced by 22% in MMJ(-) (135-106 mg/day MME, p = 0.124) and 33% in MMJ(+) (90-60 mg/day MME, p = 0.421). Conclusions: MMJ(+) improved oncology patients' ESAS scores despite opioid dose reductions and should be considered a viable adjuvant therapy for palliative management.

Association Between Medicare Star Ratings for Patient Experience and Medicare Spending per Beneficiary for US Hospitals.

OBJECTIVE: To test the association between patient experience and Centers for Medicare and Medicaid Services (CMS) spending at the hospital level. METHODS: Using CMS Hospital Compare data set, we analyzed 2014 data for CMS patient experience star ratings and the hospital Medicare Spending per Beneficiary (MSPB) Measure, which assesses price-standardized, risk-adjusted payments for services provided to Medicare beneficiaries for an episode of care from 3 days before hospital admission to 30 days following discharge. We tested the association using linear regression, adjusting for complexity of care using hospital Case Mix Index (CMI) and for socioeconomic status of the hospital patient population using Disproportionate Share Hospital (DSH) status. RESULTS: The MSPB decreased with increasing hospital patient experience ratings. After adjustment for CMI and DSH, better hospital patient experience was associated with lower spending per episode (5.6% decrease from the lowest to highest patient experience star rating). CONCLUSION: We found that better hospital patient experience was associated with lower health-care spending. Further research is needed to define what specific elements and phases of the episode of care are driving the association.

Arthroscopic Knotless Repair of the Posterior Labrum Using LabralTape.

Operative management of symptomatic labral tears of the shoulder has traditionally been the preferred treatment. Arthroscopic techniques and equipment continue to be refined and subsequent new recommendations for treatment are being developed. Contemporary techniques for arthroscopic knotless repair offer possible advantages over traditional arthroscopically tied knots. Although knotless repair of labral tears is well recognized, advancements continue to progress toward stronger fixation with reduced risks of cutting through the labrum and chondral abrasion. The suture tape used in the technique presented for arthroscopic knotless repair is stronger and flatter than traditional rounded suture and offers many potential benefits.

An approach to diabetes mellitus in hospice and palliative medicine.

Abstract Hospice and palliative medicine practitioners frequently encounter diabetes and associated complications as comorbidities in end-of-life patients. As the patient with diabetes approaches end-of-life, there comes a time when tight glycemic control can not only prove of questionable benefit, but has the potential to cause harm. The medical literature offers little guidance on managing these complications appropriately. This article identifies three distinct classifications of patients with diabetes approaching the ends of their lives due to advanced illnesses. The authors propose a specific framework to guide management in patients with diabetes and advanced disease who are relatively stable, experiencing impending death or organ failure, or actively dying. The authors provide comprehensive information on commonly used diabetic medications, with necessary considerations and dose adjustments for these populations. The goal of the approach is to address individual patient needs, provide guidance for patients and caregivers, and ultimately maximize outcomes for patients with diabetes in the palliative care setting.

Spatial relationships between water quality and pesticide application rates in agricultural watersheds.

Pesticide applications to agricultural lands in California, USA, are reported to a central data base, while data on water and sediment quality are collected by a number of monitoring programs. Data from both sources are geo-referenced, allowing spatial analysis of relationships between pesticide application rates and the chemical and biological condition of water bodies. This study collected data from 12 watersheds, selected to represent a range of pesticide usage. Water quality parameters were measured during six surveys of stream sites receiving runoff from the selected watershed areas. This study had three objectives: to evaluate the usefulness of pesticide application data in selecting regional monitoring sites, to provide information for generating and testing hypotheses about pesticide fate and effects, and to determine whether in-stream nitrate concentration was a useful surrogate indicator for regional monitoring of toxic substances. Significant correlations were observed between pesticide application rates and in-stream pesticide concentrations (p < 0.05) and toxicity (p < 0.10). In-stream nitrate concentrations were not significantly correlated with either the amount of pesticides applied, in-stream pesticide concentrations, or in-stream toxicity (all p > 0.30). Neither total watershed area nor the area in which pesticide usage was reported correlated significantly with the amount of pesticides applied, in-stream pesticide concentrations, or in-stream toxicity (all p > 0.14). In-stream pesticide concentrations and effects were more closely related to the intensity of pesticide use than to the area under cultivation.