Why Not Home?: A Study of the Impact of an Effort to Reduce Postacute Expenditures.

PURPOSE OF STUDY: Accountable Care Organizations (ACOs) aiming to reduce healthcare expenditure adopt strategies targeting costly postacute service utilization, asking "why not home?" as a part of the hospital discharge planning paradigm. This study examined the impact of an interventional approach to implement evidence-based interventions to improve transitions of care to the least restrictive next site of care on the rate of skilled nursing facility (SNF) admissions per 1,000, SNF length of stay (LOS), and total SNF cost. PRIMARY PRACTICE SETTING: The impact of the interventional approach for an ACO-attributed Medicare population, analyzing Medicare Shared Savings Plan Part A and Part B beneficiary claims data, was examined. METHODOLOGY AND SAMPLE: A pre-/postintervention analysis was conducted, for dates of service 12 months pre- and postintervention for patients admitted to any hospital within the integrated health care system. The outcome variables were defined as SNF admission rate, SNF LOS, cost of care (total SNF cost, SNF cost per admission), and hospital LOS prior to SNF discharge. RESULTS: There was early evidence of the effectiveness of the multifaceted interventions that involved the delivery of interprofessional team member education focused on the tenets of value-based care and discharging patients to the least restrictive setting, as appropriate. In the normalized data review, it was noted that the rate of SNF discharges per 1,000 patients changed from 73 per 1,000 patients in the preintervention period to 70 per 1,000 patients in the postintervention period. The total SNF cost in the postintervention period only increased by 3%, with a difference of $616,014, despite the 10% increase in the total ACO-attributed patient population during the same period. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The results of this study imply that a multifaceted intervention with aims to shift the transitional care planning paradigm toward discharging to the least restrictive next site of care is an effective strategy for ACOs with aspirations to improve the utilization and expenditure in the postacute setting. The analyses suggest that providing education to interprofessional team members that reinforces the tenets of value-based care and the importance of asking, "why not home?" for every hospitalized patient, and leveraging technology-based insights positively impact discharge rates to SNF and other ACO outcomes.

Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson's disease.

Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson's disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973-2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation.

Study of Malformin C, a Fungal Source Cyclic Pentapeptide, as an Anti-Cancer Drug.

Malformin C, a fungal cyclic pentapeptide, has been claimed to have anti-cancer potential, but no in vivo study was available to substantiate this property. Therefore, we conducted in vitro and in vivo experiments to investigate its anti-cancer effects and toxicity. Our studies showed Malformin C inhibited Colon 38 and HCT 116 cell growth dose-dependently with an IC50 of 0.27±0.07µM and 0.18±0.023µM respectively. This inhibition was explicated by Malformin C's effect on G2/M arrest. Moreover, we observed up-regulated expression of phospho-histone H2A.X, p53, cleaved CASPASE 3 and LC3 after Malformin C treatment, while the apoptosis assay indicated an increased population of necrotic and late apoptotic cells. In vivo, the pathological study exhibited the acute toxicity of Malformin C at lethal dosage in BDF1 mice might be caused by an acute yet subtle inflammatory response, consistent with elevated IL-6 in the plasma cytokine assay. Further anti-tumor and toxicity experiments proved that 0.3mg/kg injected weekly was the best therapeutic dosage of Malformin C in Colon 38 xenografted BDF1 mice, whereas 0.1mg/kg every other day showed no effect with higher resistance, and 0.9mg/kg per week either led to fatal toxicity in seven-week old mice or displayed no advantage over 0.3mg/kg group in nine-week old mice. Overall, we conclude that Malformin C arrests Colon 38 cells in G2/M phase and induces multiple forms of cell death through necrosis, apoptosis and autophagy. Malformin C has potent cell growth inhibition activity, but the therapeutic index is too low to be an anti-cancer drug.