Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses to Reduce Nonbeneficial Intensive Care Unit Treatments: Protocol for a Multicenter Quality Improvement Study.

BackgroundInvasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters. For patients with advanced medical illnesses receiving aggressive ICU treatments, TLTs can promote effective dialogue, develop consensus in decision making, and set rational boundaries to treatments based on patients' goals of care.ObjectiveThe aim of this study will be to examine whether a multicomponent quality-improvement strategy that uses protocoled TLTs as the default ICU care-planning approach for critically ill patients with advanced medical illnesses will decrease duration and intensity of nonbeneficial ICU care without changing hospital mortality.MethodsThis study will be conducted in medical ICUs of three public teaching hospitals in Los Angeles County. In Aim 1, we will conduct focus groups and semistructured interviews with key stakeholders to identify facilitators and barriers to implementing TLTs among ICU patients with advanced medical illnesses. In Aim 2, we will train clinicians to use protocol-enhanced TLTs as the default communication and care-planning approach in patients with advanced medical illnesses who receive invasive ICU treatments. Eligible patients will be those who the treating ICU physicians consider to be at high risk for nonbeneficial treatments according to guidelines from the Society of Critical Care Medicine. ICU physicians will be trained to use the TLT protocol through a curriculum of didactic lectures, case discussions, and simulations utilizing actors as family members in role-playing scenarios. Family meetings will be scheduled by trained care managers. The improvement strategy will be implemented sequentially in the three participating hospitals, and outcomes will be evaluated using a before-and-after study design. Key process outcomes will include frequency, timing, and content of family meetings. The primary clinical outcome will be ICU length of stay. Secondary outcomes will include hospital length of stay, days receiving life-sustaining treatments (eg, mechanical ventilation, vasopressors, and renal replacement therapy), number of attempts at cardiopulmonary resuscitation, frequency of invasive ICU procedures, and disposition from hospitalization.ResultsThe study began in August 2017. The implementation of interventions and data collection were completed at two of the three hospitals. As of September 2019, the study was at the postintervention stage at the third hospital. We have completed focus groups with physicians at each medical center (N=29) and interviews of family members and surrogate decision makers (N=18). The study is expected to be completed in the first quarter of 2020, and results are expected to be available in mid-2020.ConclusionsThe successful completion of the aims in this proposal may identify a systematic approach to improve communication and shared decision making and to reduce nonbeneficial invasive treatments for ICU patients with advanced medical illnesses.International registered report identifier (irrid)DERR1-10.2196/16301

Global Wellposedness for a Modified Critical Dissipative Quasi-Geostrophic Equation

In this paper we consider the following modified quasi-geostrophic equation \partial_{t}\theta+u\cdot\nabla\theta+\nu |D|^{\alpha}\theta=0, \quad u=|D|^{\alpha-1}\mathcal{R}^{\bot}\theta,\quad x\in\mathbb{R}^2 with $\nu>0$ and $\alpha\in ]0,1[\,\cup \,]1,2[$. When $\alpha\in]0,1[$, the equation was firstly introduced by Constantin, Iyer and Wu in \cite{ref ConstanIW}. Here, by using the modulus of continuity method, we prove the global well-posedness of the system with the smooth initial data. As a byproduct, we also show that for every $\alpha\in ]0,2[$, the Lipschitz norm of the solution has a uniform exponential bound.Comment: In this version we extend the range of $\alpha$ from (0,1) to (0,2), we also show that for every $\alpha\in (0,2)$, the Lipschitz norm of the solution has a uniform exponential bound. 27page

Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c.

AimTo determine whether successful treatment with directacting antivirals (DAA) is associated with improvements in hemoglobin A1c (HbA1c) and if type 2 diabetes mellitus (T2DM) or metabolic syndrome affects sustained virologic response (SVR).MethodsWe performed a retrospective analysis of all hepatitis C virus (HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment (SVR12).ResultsA total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2DM. Within that cohort, patients who achieved SVR12 had lower mean HbA1c pre treatment (7.35 vs 8.60, P = 0.02), and lower mean HbA1c post-treatment compared to non-responders (6.55 vs 8.61, P = 0.01). The mean reduction in HbA1c after treatment was greater for those who achieved SVR12 than for non-responders (0.79 vs 0.01, P = 0.03). In adjusted models, patients that achieved SVR12 were more likely to have a HbA1c decrease of ≥ 0.5 than those that did not achieve SVR12 (adjusted OR = 7.24, 95%CI: 1.22-42.94).ConclusionIn HCV patients with T2DM, successful treatment with DAA was associated with a significant reduction in HbA1c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore, the presence of T2DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA

A Comparison between Deep Neural Nets and Kernel Acoustic Models for Speech Recognition

We study large-scale kernel methods for acoustic modeling and compare to DNNs on performance metrics related to both acoustic modeling and recognition. Measuring perplexity and frame-level classification accuracy, kernel-based acoustic models are as effective as their DNN counterparts. However, on token-error-rates DNN models can be significantly better. We have discovered that this might be attributed to DNN's unique strength in reducing both the perplexity and the entropy of the predicted posterior probabilities. Motivated by our findings, we propose a new technique, entropy regularized perplexity, for model selection. This technique can noticeably improve the recognition performance of both types of models, and reduces the gap between them. While effective on Broadcast News, this technique could be also applicable to other tasks.Comment: arXiv admin note: text overlap with arXiv:1411.400

Race affects SVR12 in a large and ethnically diverse hepatitis C-infected patient population following treatment with direct-acting antivirals: Analysis of a single-center Department of Veterans Affairs cohort.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct-acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African-Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non-CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA-treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single-center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African-American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non-SVR. African-Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5-4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26-0.68) was also a significant predictor of non-SVR. In a single-center VA population on DAAs, African-Americans were less likely than White people to reach SVR12 when adjusting for covariates

Understanding the edge effect in TASEP with mean-field theoretic approaches

We study a totally asymmetric simple exclusion process (TASEP) with one defect site, hopping rate $q<1$, near the system boundary. Regarding our system as a pair of uniform TASEP's coupled through the defect, we study various methods to match a \emph{finite} TASEP and an \emph{infinite} one across a common boundary. Several approximation schemes are investigated. Utilizing the finite segment mean-field (FSMF) method, we set up a framework for computing the steady state current $J$ as a function of the entry rate $$ and $q$. For the case where the defect is located at the entry site, we obtain an analytical expression for $J(\alpha, q)$ which is in good agreement with Monte Carlo simulation results. When the defect is located deeper in the bulk, we refined the scheme of MacDonald, et.al. [Biopolymers, \textbf{6}, 1 (1968)] and find reasonably good fits to the density profiles before the defect site. We discuss the strengths and limitations of each method, as well as possible avenues for further studies.Comment: 16 pages, 4 figure

Targeted long-read sequencing reveals clonally expanded HBV-associated chromosomal translocations in patients with chronic hepatitis B

Chronic HBV; Clonal expansion; Targeted sequencingVHB crónico; Expansión clónica; Secuenciación dirigidaVHB crònic; Expansió clonal; Seqüenciació dirigidaBackground & Aims HBV infects over 257 million people worldwide and is associated with the development of hepatocellular carcinoma (HCC). Integration of HBV DNA into the host genome is likely a key driver of HCC oncogenesis. Here, we utilise targeted long-read sequencing to determine the structure of HBV DNA integrations as well as full isoform information of HBV mRNA with more accurate quantification than traditional next generation sequencing platforms. Methods DNA and RNA were isolated from fresh frozen liver biopsies collected within the GS-US-174-0149 clinical trial. A pan-genotypic panel of biotinylated oligos was developed to enrich for HBV sequences from sheared genomic DNA (∼7 kb) and full-length cDNA libraries from poly-adenylated RNA. Samples were sequenced on the PacBio long-read platform and analysed using a custom bioinformatic pipeline. Results HBV-targeted long-read DNA sequencing generated high coverage data spanning entire integrations. Strikingly, in 13 of 42 samples (31%) we were able to detect HBV sequences flanked by 2 different chromosomes, indicating a chromosomal translocation associated with HBV integration. Chromosomal translocations were unique to each biopsy sample, suggesting that each originated randomly, and in some cases had evidence of clonal expansion. Using targeted long-read RNA sequencing, we determined that upwards of 95% of all HBV transcripts in patients who are HBeAg-positive originate from cccDNA. In contrast, patients who are HBeAg-negative expressed mostly HBsAg from integrations. Conclusions Targeted lso-Seq allowed for accurate quantitation of the HBV transcriptome and assignment of transcripts to either cccDNA or integration origins. The existence of multiple unique HBV-associated inter-chromosomal translocations in non-HCC CHB patient liver biopsies suggests a novel mechanism with mutagenic potential that may contribute to progression to HCC

Analyzing Norm Violations in Live-Stream Chat

Toxic language, such as hate speech, can deter users from participating in online communities and enjoying popular platforms. Previous approaches to detecting toxic language and norm violations have been primarily concerned with conversations from online forums and social media, such as Reddit and Twitter. These approaches are less effective when applied to conversations on live-streaming platforms, such as Twitch and YouTube Live, as each comment is only visible for a limited time and lacks a thread structure that establishes its relationship with other comments. In this work, we share the first NLP study dedicated to detecting norm violations in conversations on live-streaming platforms. We define norm violation categories in live-stream chats and annotate 4,583 moderated comments from Twitch. We articulate several facets of live-stream data that differ from other forums, and demonstrate that existing models perform poorly in this setting. By conducting a user study, we identify the informational context humans use in live-stream moderation, and train models leveraging context to identify norm violations. Our results show that appropriate contextual information can boost moderation performance by 35\%.Comment: 17 pages, 8 figures, 15 table

Is microstructural homogeneity the answer to hydrogen embrittlement resistance?

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