A Bayesian data assimilation framework for lake 3D hydrodynamic models with a physics-preserving particle filtering method using SPUX-MITgcm v1

We present a Bayesian inference for a three-dimensional hydrodynamic model of Lake Geneva with stochastic weather forcing and high-frequency observational datasets. This is achieved by coupling a Bayesian inference package, SPUX, with a hydrodynamics package, MITgcm, into a single framework, SPUX-MITgcm. To mitigate uncertainty in the atmospheric forcing, we use a smoothed particle Markov chain Monte Carlo method, where the intermediate model state posteriors are resampled in accordance with their respective observational likelihoods. To improve the assimilation of remotely sensed temperature, we develop a bi-directional Long Short-Term Memory (Bi-LSTM) neural network to estimate lake skin temperature from a history of hydrodynamic bulk temperature predictions and atmospheric data. This study analyzes the benefit and costs of such state of the art computationally expensive calibration and assimilation method for lakes.

Impact of overall survival (OS) as a function of facility caseload on feasibility of referral of radical prostatectomy (RP) to higher volume facilities.

363 Background: We recently reported a significant all-cause mortality (ACM) risk reduction associated with higher annual caseload for RP (PMID 31398279). Four volume groups (VG) were defined as VG1: <50th, VG2: 50th-74th, VG3: 75th-89th and VG4: top 10 percentile of caseload. The adjusted OS difference between VG1 and VG4 at 90th percentile survivorship reached 13.2 months, HR 1.30 (p<0.0001). Here we explore this economics of referral to VG4. Methods: Using a Markov model, we designed 4 scenarios (Sc) where 100,000 RPs were performed. In Sc 1 all RPs were performed at VG1; in Sc 2, 3 & 4, all RPs were performed at VG2, 3 &4 respectively. Subjects were followed for up to 20 years after RP. Survival and costs of care for each Sc were recorded. Probabilities of PSA recurrence (PSAR), development of metastatic disease (Met), cancer specific mortality (CSM) and ACM were adjusted for each VG according to the published HRs. Savings resulting from fewer recurrences, avoidance of salvage radiation therapy (SRT) and management of fewer Met were calculated. Standard discounting at 3% were applied to costs and benefits. Survival benefit and costs savings associated with making referrals from VG1, VG2, or VG3 centers to VG4 center were calculated. Using a willingness to pay (WTP) of $50K per life years gained (LYG), the maximum referral costs (MRC) were calculated. Results: Referral from a VG1 to a VG4 center was associated with highest OS benefit of 720 LYG at 20 years of follow up per 1000 referrals (PKR). Within a WTP of $50K, MRC of up to $37K was cost effective- Table. Conclusions: Given the survival benefit associated with performing RP at facility with high annual caseload, significant resources could be allocated to making a referral possible while still remaining within cost effectiveness boundaries.[Table: see text]

Application of the ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale to Assess the Value of Abiraterone and Enzalutamide in Advanced Prostate Cancer

PURPOSE: As novel hormonal therapies, such as abiraterone and enzalutamide, move into earlier stages of treatment of advanced prostate cancer, there are significant cost implications. We used the ASCO Value Framework (AVF) and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) to quantify and compare the incremental clinical benefit and costs of these agents in the metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) settings. METHODS: We searched PubMed for randomized phase III trials of abiraterone and enzalutamide in mCRPC and mCSPC. Incremental clinical benefit was quantified using the AVF and ESMO-MCBS by 2 independent assessors. Incremental drug costs were calculated using average wholesale prices (AWPs) from the RED BOOK Online. RESULTS: In mCRPC, 2 abiraterone trials (COU-AA-301 and COU-AA-302) and 2 enzalutamide trials (AFFIRM and PREVAIL) met search criteria. AVF scores ranged from 46.3 to 66.6, suggesting clinical benefit; ESMO-MCBS scores ranged from 3 to 5, with lower clinical benefit in the mCRPC predocetaxel setting. The overall incremental AWP ranged from $83,460.94 to $205,128.85. In mCSPC, 4 trials met criteria (LATITUDE, STAMPEDE, ENZAMET, and ARCHES; AVF scores were 79.8, 33.3, 59, and 17, respectively). All of the studies showed benefit except ARCHES. By ESMO-MCBS, both LATITUDE and STAMPEDE showed benefit (score for 4 for both studies); ENZAMET and ARCHES were not evaluable. The overall cost of treatment was significantly higher in the mCSPC setting. CONCLUSION: The AVF and ESMO-MCBS frameworks generated slightly different results but suggested that abiraterone and enzalutamide show clinical benefit in both mCRPC and mCSPC but trended to lower clinical benefit and increased costs in earlier disease stages. Further refinement of the AVF and ESMO-MCBS is needed to facilitate their use and their ability to inform clinical practice in a rapidly changing treatment landscape.

The ecological efficiency assessment in the system of management

The article presents models and methods of environmental efficiency assessment. The analysis of methodological approaches to environmental efficiency assessment has been carried out. The research concludes that the indicators of ecological management benefit and costs and nature protection activity are key criteria in environmental efficiency estimation.

Abstract TP124: Tapered Stent Geometry Provides Strong Hemodynamic Effect After Carotid Stenting

Objective: In the last years, development of materials allowed notably improvements in interventional approach to stroke. Tapered stents were specifically designed for extracranial carotid stenting (CAS) to deal with vessels mismatch decreasing the risk of thrombosis. Nevertheless, as to whether the stent geometry may affect the hemodynamic consequences of CAS remains uncertain. This study aims to investigate the impact of stent configuration on postprocedural sustained hemodynamic depression (HD) requiring action of care after carotid stenting (CAS). Methods: Data on 391 consecutive CAS performed over a 4-year period (2011-2014) were reviewed. Postprocedural sustained HD was defined as any severe hypotension (<90mmHg) or bradicardia (<50beats/min) persisting at >2 measurements after the end of the procedure and requiring care support or delaying hospital discharge. Stent configuration (tapered or straight) was tested for association with sustained HD using multivariable models adjusted for other confounders (medical therapy, comorbidities, symptoms, stenosis, carotid plaque and demographics).The relation with stroke and death outcomes within 30 days of treatment was also analyzed. Results: Mean age of patients was 70.7y + 7.14 and 66.2% were males. Sustained HD developed after 144 (36.8%) CAS. Tapered stents were applied in 289 (73.9%) CAS, and more frequently in patients with higher degree of stenosis (mean 79% vs 77%, in tapered and straight stents respectively; P=0.007) or asymptomatic (93.8% vs. 85.3% in tapered and straight stents respectively;P=0.012). Diabetes (HR 1.6, 95% CI, 1.01-2.44;P=0.044) and tapered stent configuration (HR, 1.7, 95% CI, 1.05-2.82;P=0.033) were the only factors that showed independent association with sustained HD. At 30-day, 3 strokes and no death occurred. There was no statistically significant association between 30-day outcomes and sustained HD depression or stent configuration. Conclusions: A strong hemodynamic effect, requiring additional actions of care or prolonged hospital stay, is expected after CAS when using tapered stent configuration. These findings alert on the overall benefit and costs of CAS and the requirements for accurate material selection especially in diabetic patients.

Should University Students Be Vaccinated against Meningococcal Disease in Canada?

OBJECTIVE: To evaluate the benefit and costs of vaccination of university students against invasive meningococcal disease (IMD) in Canada.METHODS: Published studies were reviewed and a simulation model was used.RESULTS: IMD risk seems to be of low magnitude, but consequences can be dramatic. Over a 10-year period, IMD risk reduction would be slightly greater using a monovalent C conjugate vaccine than a quadrivalent polysaccharide vaccine. From a societal perspective, costs per quality-adjusted life-years gained would be between $135,000 and $698,000, according to epidemiological scenarios and with vaccine purchase prices between $35 and $50 per dose.CONCLUSIONS: Economic indices exceed proposed criteria for cost effective public health programs, but from the perspective of students and parents, the cost of vaccination might be worth the benefit.