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Utilization of Palliative Care for Patients with Acute Kidney Injury and COVID-19 (S541) [Meeting Abstract]

Scherer, J; Rau, M; Qian, Y; Soomro, Q; Sullivan, R; Zhong, H; Linton, J; Chodosh, J; Charytan, D
Outcomes: 1. Understand the historical use of palliative care for patients with acute kidney injury (AKI) 2. Describe the use of palliative care for patients with AKI and COVID-19 during the surge at our institution 3. Describe the associations of palliative care with subsequent health care utilization such as hospice use, ICU time, and mechanical ventilation Original Research Background: Acute kidney injury (AKI) is a common morbidity seen in patients with COVID-19 and is associated with high mortality. Palliative care is valuable for these patients yet is historically underused in AKI. Research Objectives: To describe the use of palliative care and subsequent health care utilization by COVID-19 patients with AKI.
Method(s): A retrospective analysis of NYU's electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. AKI was defined by the AKI Network creatinine criteria. Regression models examined characteristics associated with a receiving palliative care and discharge to hospice versus death in the hospital.
Result(s): Patientswith COVID-19 and AKI were more likely than those without AKI to receive palliative care (42% vs 7%, p < 0.001); however, consults came significantly later (10 days from admission vs 5 days, p < 0.001). 66% of patients initiated on renal replacement therapy (RRT) received palliative care versus 37% (p < 0.001) of those with AKI not on RRT, also later in timing (12 days from admission vs 9 days, p = 0.002). Patients with AKI had a significantly longer stay, more ICU admissions, use of mechanical ventilation, discharges to hospice (6% vs 3%), and changes in code status (34% vs 7%, p < 0.001) than those without AKI. Among those who received palliative care, AKI both without RRT (adjusted odds ratio [aOR] 0.51, 95% confidence interval [CI] 0.27-0.95) and with RRT (aOR 0.18, 95% CI 0.04-0.67) was associated with a lower likelihood of discharge to hospice versus hospital death compared to those without AKI.
Conclusion(s): Palliative care was used more for patients with AKI and COVID-19 than historically reported, yet this consultation came later in the hospital course and did not avoid invasive interventions despite high mortality. Implications for Research, Policy, or Practice: These data can lead to further exploration of earlier timing of palliative care consultation in AKI.
Copyright
EMBASE:2017644107
ISSN: 1873-6513
CID: 5240182

mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis

Palma, Jose-Alberto; Martinez, Jose; Millar Vernetti, Patricio; Ma, Thong; Perez, Miguel A; Zhong, Judy; Qian, Yingzhi; Dutta, Suman; Maina, Katherine N; Siddique, Ibrar; Bitan, Gal; Ades-Aron, Benjamin; Shepherd, Timothy M; Kang, Un J; Kaufmann, Horacio
BACKGROUND:Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. OBJECTIVE:To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants. METHODS:Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976). RESULTS:The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression. CONCLUSIONS:Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.
PMID: 35040506
ISSN: 1531-8257
CID: 5131432

Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 Surge

Scherer, Jennifer S; Qian, Yingzhi; Rau, Megan E; Soomro, Qandeel H; Sullivan, Ryan; Linton, Janelle; Zhong, Judy; Chodosh, Joshua; Charytan, David M
BACKGROUND AND OBJECTIVES/OBJECTIVE:AKI is a common complication of coronavirus disease 2019 (COVID-19) and is associated with high mortality. Palliative care, a specialty that supports patients with serious illness, is valuable for these patients but is historically underutilized in AKI. The objectives of this paper are to describe the use of palliative care in patients with AKI and COVID-19 and their subsequent health care utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We conducted a retrospective analysis of New York University Langone Health electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. Regression models were used to examine characteristics associated with receiving a palliative care consult. RESULTS:=0.002). Despite greater use of palliative care, patients with AKI had a significantly longer length of stay, more intensive care unit admissions, and more use of mechanical ventilation. Those with AKI did have a higher frequency of discharges to inpatient hospice (6% versus 3%) and change in code status (34% versus 7%) than those without AKI. CONCLUSIONS:Palliative care was utilized more frequently for patients with AKI and COVID-19 than historically reported in AKI. Despite high mortality, consultation occurred late in the hospital course and was not associated with reduced initiation of life-sustaining interventions. PODCAST/UNASSIGNED:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_24_CJN11030821.mp3.
PMID: 35210281
ISSN: 1555-905x
CID: 5172422

Factors associated with hospital admission and severe outcomes for older patients with COVID-19

Kim, Jiyu; Blaum, Caroline; Ferris, Rosie; Arcila-Mesa, Mauricio; Do, Hyungrok; Pulgarin, Claudia; Dolle, Johanna; Scherer, Jennifer; Kalyanaraman Marcello, Roopa; Zhong, Judy
BACKGROUND:Morbidity and death due to coronavirus disease 2019 (COVID-19) experienced by older adults in nursing homes have been well described, but COVID-19's impact on community-living older adults is less studied. Similarly, the previous ambulatory care experience of such patients has rarely been considered in studies of COVID-19 risks and outcomes. METHODS:To investigate the relationship of advanced age (65+), on risk factors associated with COVID-19 outcomes in community-living elders, we identified an electronic health records cohort of older patients aged 65+ with laboratory-confirmed COVID-19 with and without an ambulatory care visit in the past 24 months (n = 47,219) in the New York City (NYC) academic medical institutions and the NYC public hospital system from January 2020 to February 2021. The main outcomes are COVID-19 hospitalization; severe outcomes/Intensive care unit (ICU), intubation, dialysis, stroke, in-hospital death), and in-hospital death. The exposures include demographic characteristics, and those with ambulatory records, comorbidities, frailty, and laboratory results. RESULTS:The 31,770 patients with an ambulatory history had a median age of 74 years; were 47.4% male, 24.3% non-Hispanic white, 23.3% non-Hispanic black, and 18.4% Hispanic. With increasing age, the odds ratios and attributable fractions of sex, race-ethnicity, comorbidities, and biomarkers decreased except for dementia and frailty (Hospital Frailty Risk Score). Patients without ambulatory care histories, compared to those with, had significantly higher adjusted rates of COVID-19 hospitalization and severe outcomes, with strongest effect in the oldest group. CONCLUSIONS:In this cohort of community-dwelling older adults, we provided evidence of age-specific risk factors for COVID-19 hospitalization and severe outcomes. Future research should explore the impact of frailty and dementia in severe COVID-19 outcomes in community-living older adults, and the role of engagement in ambulatory care in mitigating severe disease.
PMID: 35179781
ISSN: 1532-5415
CID: 5175772

A Joint Fairness Model with Applications to Risk Predictions for Under-represented Populations

Do, Hyungrok; Nandi, Shinjini; Putzel, Preston; Smyth, Padhraic; Zhong, Judy
In data collection for predictive modeling, under-representation of certain groups, based on gender, race/ethnicity, or age, may yield less-accurate predictions for these groups. Recently, this issue of fairness in predictions has attracted significant attention, as data-driven models are increasingly utilized to perform crucial decision-making tasks. Existing methods to achieve fairness in the machine learning literature typically build a single prediction model in a manner that encourages fair prediction performance for all groups. These approaches have two major limitations: i) fairness is often achieved by compromising accuracy for some groups; ii) the underlying relationship between dependent and independent variables may not be the same across groups. We propose a Joint Fairness Model (JFM) approach for logistic regression models for binary outcomes that estimates group-specific classifiers using a joint modeling objective function that incorporates fairness criteria for prediction. We introduce an Accelerated Smoothing Proximal Gradient Algorithm to solve the convex objective function, and present the key asymptotic properties of the JFM estimates. Through simulations, we demonstrate the efficacy of the JFM in achieving good prediction performance and across-group parity, in comparison with the single fairness model, group-separate model, and group-ignorant model, especially when the minority group's sample size is small. Finally, we demonstrate the utility of the JFM method in a real-world example to obtain fair risk predictions for under-represented older patients diagnosed with coronavirus disease 2019 (COVID-19). This article is protected by copyright. All rights reserved.
PMID: 35142367
ISSN: 1541-0420
CID: 5176122

COVID-19 Pandemic as a Change Agent in the Structure and Practice of Statistical Consulting Centers

Lee, Shing; Bagiella, Emilia; Vaughan, Roger; Govindarajulu, Usha; Christos, Paul; Esserman, Denise; Zhong, Hua; Kim, Mimi
When New York City (NYC) became an epicenter of the COVID-19 pandemic in the spring of 2020, statistical consulting centers at academic medical institutions in the area were immediately inundated with requests from hospital leadership and researchers for methodological support to address different aspects of the outbreak. Statisticians suddenly had to pivot from their usual responsibilities to focus entirely on COVID-19 work, and consulting centers had to devise innovative strategies to restructure their workflow and develop new infrastructure to address the acute demand for support. As statisticians from seven NYC-area institutions, we share our experiences and lessons learned during the pandemic, with the hope that this will lead not only to better preparedness for future public health crises when the skills and expertise of statisticians are critically needed, but also to lasting improvements to the structure and practice of statistical consulting centers.
SCOPUS:85124343306
ISSN: 0003-1305
CID: 5165982

Reinforcement learning assisted oxygen therapy for COVID-19 patients under intensive care

Zheng, Hua; Zhu, Jiahao; Xie, Wei; Zhong, Judy
BACKGROUND:Patients with severe Coronavirus disease 19 (COVID-19) typically require supplemental oxygen as an essential treatment. We developed a machine learning algorithm, based on deep Reinforcement Learning (RL), for continuous management of oxygen flow rate for critically ill patients under intensive care, which can identify the optimal personalized oxygen flow rate with strong potentials to reduce mortality rate relative to the current clinical practice. METHODS:We modeled the oxygen flow trajectory of COVID-19 patients and their health outcomes as a Markov decision process. Based on individual patient characteristics and health status, an optimal oxygen control policy is learned by using deep deterministic policy gradient (DDPG) and real-time recommends the oxygen flow rate to reduce the mortality rate. We assessed the performance of proposed methods through cross validation by using a retrospective cohort of 1372 critically ill patients with COVID-19 from New York University Langone Health ambulatory care with electronic health records from April 2020 to January 2021. RESULTS:The mean mortality rate under the RL algorithm is lower than the standard of care by 2.57% (95% CI: 2.08-3.06) reduction (P < 0.001) from 7.94% under the standard of care to 5.37% under our proposed algorithm. The averaged recommended oxygen flow rate is 1.28 L/min (95% CI: 1.14-1.42) lower than the rate delivered to patients. Thus, the RL algorithm could potentially lead to better intensive care treatment that can reduce the mortality rate, while saving the oxygen scarce resources. It can reduce the oxygen shortage issue and improve public health during the COVID-19 pandemic. CONCLUSIONS:A personalized reinforcement learning oxygen flow control algorithm for COVID-19 patients under intensive care showed a substantial reduction in 7-day mortality rate as compared to the standard of care. In the overall cross validation cohort independent of the training data, mortality was lowest in patients for whom intensivists' actual flow rate matched the RL decisions.
PMID: 34920724
ISSN: 1472-6947
CID: 5109942

Respiratory Mechanics and Association With Inflammation in COVID-19-Related ARDS

Bhatt, Alok; Deshwal, Himanshu; Luoma, Kelsey; Fenianos, Madelin; Hena, Kerry; Chitkara, Nishay; Zhong, Hua; Mukherjee, Vikramjit
BACKGROUND:The novel coronavirus-associated ARDS (COVID-19 ARDS) often requires invasive mechanical ventilation. A spectrum of atypical ARDS with different phenotypes (high vs low static compliance) has been hypothesized in COVID-19. METHODS:test, chi-square test, ANOVA test, and Pearson correlation was used to identify relationship between subject variables and respiratory mechanics. The primary outcome was duration of mechanical ventilation. Secondary outcomes were correlation between fluid status, C- reactive protein, PEEP, and D-dimer with respiratory and ventilatory parameters. RESULTS:= .02). CONCLUSIONS:In our cohort of mechanically ventilated COVID-19 ARDS subjects, high PEEP and D-dimer were associated with increase in physiologic dead space without significant effect on oxygenation, raising the question of potential microvascular dysfunction.
PMID: 34521759
ISSN: 1943-3654
CID: 5038882

Preexisting immune-mediated inflammatory disease is associated with improved survival and increased toxicity in melanoma patients who receive immune checkpoint inhibitors

Gulati, Nicholas; Celen, Arda; Johannet, Paul; Mehnert, Janice M; Weber, Jeffrey; Krogsgaard, Michelle; Osman, Iman; Zhong, Judy
BACKGROUND:Immune-related adverse events (irAEs) are common, clinically significant autoinflammatory toxicities observed with immune checkpoint inhibitors (ICI). Preexisting immune-mediated inflammatory disease (pre-IMID) is considered a relative contraindication to ICI due to the risk of inciting flares. Improved understanding of the risks and benefits of treating pre-IMID patients with ICI is needed. METHODS:We studied melanoma patients treated with ICI and enrolled in a prospective clinicopathological database. We compiled a list of 23 immune-mediated inflammatory diseases and evaluated their presence prior to ICI. We tested the associations between pre-IMID and progression-free survival (PFS), overall survival (OS), and irAEs. RESULTS:In total, 483 melanoma patients were included in the study; 74 had pre-IMID and 409 did not. In patients receiving ICI as a standard of care (SoC), pre-IMID was significantly associated with irAEs (p = 0.04) as well as improved PFS (p = 0.024) and OS (p = 0.007). There was no significant association between pre-IMID and irAEs (p = 0.54), PFS (p = 0.197), or OS (p = 0.746) in patients treated through a clinical trial. Pre-IMID was significantly associated with improved OS in females (p = 0.012), but not in males (p = 0.35). CONCLUSIONS:The dichotomy of the impact of pre-IMID on survival and irAEs in SoC versus clinical trial patients may reflect the inherit selection bias in patients accrued in clinical trials. Future mechanistic work is required to better understand the differences in outcomes between female and male pre-IMID patients. Our data challenge the notion that clinicians should avoid ICI in pre-IMID patients, although close monitoring and prospective clinical trials evaluating ICI in this population are warranted.
PMCID:8559502
PMID: 34647433
ISSN: 2045-7634
CID: 5062002

P6. Spinopelvic alignment changes between seated and standing positions in pre and post total hip replacement patients [Meeting Abstract]

Balouch, E; Zhong, J; Jain, D; O'Malley, N; Maglaras, C; Schwarzkopf, R; Buckland, A J
BACKGROUND CONTEXT: The inter-relationship between the hip and spine has been increasingly studied in recent years, particularly as it pertains to the effect of spinal deformity and hip osteoarthritis (OA). Changing from standing (ST) to seated (SE) requires rotation of the femur from an almost vertical plane to the horizontal. OA of the hip significantly limits hip extension, resulting in less ability to recruit pelvic tilt (PT) in ST, and requiring increased PT in SE to compensate for loss of hip flexion. To date, the effect of total hip arthroplasty (THA) in altering spinopelvic SE and ST mechanics has not been reported. PURPOSE: To investigate the change in spinopelvic alignment parameters between seated and standing positions in pre and post THA patients. STUDY DESIGN/SETTING: Retrospective review at a single academic institution. PATIENT SAMPLE: Adult patients undergoing THA with full body sitting and standing radiographs pre- and post-THA. OUTCOME MEASURES: Spinopelvic alignment measures including pelvic incidence (PI), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS), sagittal vertical axis (SVA), pelvic incidence and lumbar lordosis mismatch (PI-LL), and lumbar lordosis (LL).
METHOD(S): Patients >=18yo undergoing THA for hip OA with full spine SE and ST radiographs pre and post THA were included. Spinopelvic alignment was analyzed pre-THA and post-THA in both ST and SE positions in a relaxed posture with the fingers on the clavicles. Paired t-test analysis was performed to compare Pre-and Post-THA groups. The effect of TL deformity (SVA>50, TPA>20, PI-LL>10) on these changes was also analyzed. Statistical significance set at p<0.05.
RESULT(S): There were 192 patients assessed. 179 patients had thoracolumbar (TL) deformity; TPA>20 (N=46), PI-LL>10 (N=55), and SVA>50 (N=78). In standing position, patients have a significant reduction in SVA post THA vs pre THA (34.09+/-42.69 vs 45.03+/-46.87, p=0.001) as a result of an increase in PT (15.7+/-9.74 o vs 14.6+/-9.88o,p=0.028), without significant changes in spinal alignment parameters including lumbar lordosis (-51.26+/-14.59 vs -50.26+/-14.87, p=0.092), thoracic kyphosis (35.98+/-12.72 vs 35.40+/-13.16, p=0.180), sacral slope (38.15+/-10.77 vs 38.83+/-11.31, p=0.205), T1 pelvic angle (14.22+/-9.94 vs 14.51+/-10.13, p=0.053) and PI-LL mismatch (2.59+/-14.61 vs 3.35+/-14.92, p=0.183). This change in ST_SVA was larger in patients with TL deformity, specifically in those with SVA>50 (61.29+/-45.69 vs 89.48+/-35.91, p=0.001), in PI-LL > 10 (59.08+/-45.49 vs 73.36+/-48.50, p=0.001) and in TPA>20 subsets (62.14+/-49.94 vs 82.28+/-49.55, p=0.001). When moving from ST to SE, the DELTAPT was reduced post THA (16.70+/-15.27o vs 20.85+/-17.27o, p=0.001) in addition to a smaller SE_PT vs pre-THA (32.41+/-14.47 vs 35.46+/-14.20, p=0.006).
CONCLUSION(S): Post Total Hip Arthroplasty (THA), patients demonstrated an increased recruitment of pelvic retroversion to achieve a better global balance by reduction in standing SVA. This compensation was achieved solely by greater mobility of their hip and pelvis, and without a significant change in spinal alignment. ST_SVA reduction was more pronounced in patients with thoracolumbar (TL) spinal deformity (SVA>50, TPA>20, PI-LL>10). On the converse, PT was reduced in sitting (SE) post-THA compared to pre-THA, and the compensatory change in PT was also reduced between ST and SE as a result of restoration of hip flexion. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
Copyright
EMBASE:2014002131
ISSN: 1529-9430
CID: 4971692