IU Indianapolis ScholarWorks :: Browsing by Author "Xu, Chenjia"

Browsing by Author "Xu, Chenjia"

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Applications of Time to Event Analysis in Clinical Data
(2021-12) Xu, Chenjia; Gao, Sujuan; Liu, Hao; Zang, Yong; Zhang, Jianjun; Zhao, Yi
Survival analysis has broad applications in diverse research areas. In this dissertation, we consider an innovative application of survival analysis approach to phase I dose-finding design and the modeling of multivariate survival data. In the first part of the dissertation, we apply time to event analysis in an innovative dose-finding design. To account for the unique feature of a new class of oncology drugs, T-cell engagers, we propose a phase I dose-finding method incorporating systematic intra-subject dose escalation. We utilize survival analysis approach to analyze intra-subject dose-escalation data and to identify the maximum tolerated dose. We evaluate the operating characteristics of the proposed design through simulation studies and compare it to existing methodologies. The second part of the dissertation focuses on multivariate survival data with semi-competing risks. Time-to-event data from the same subject are often correlated. In addition, semi-competing risks are sometimes present with correlated events when a terminal event can censor other non-terminal events but not vice versa. We use a semiparametric frailty model to account for the dependence between correlated survival events and semi-competing risks and adopt penalized partial likelihood (PPL) approach for parameter estimation. In addition, we investigate methods for variable selection in semi-parametric frailty models and propose a double penalized partial likelihood (DPPL) procedure for variable selection of fixed effects in frailty models. We consider two penalty functions, least absolute shrinkage and selection operator (LASSO) and smoothly clipped absolute deviation (SCAD) penalty. The proposed methods are evaluated in simulation studies and illustrated using data from Indianapolis-Ibadan Dementia Project.
Association of Hypercholesterolemia with Alzheimer’s Disease Pathology and Cerebral Amyloid Angiopathy
(IOS Press, 2020-02-18) Xu, Chenjia; Apostolova, Liana G.; Oblak, Adrian L.; Gao, Sujuan; Biostatistics, School of Public Health
Background: Animal studies have shown that diet-induced hypercholesterolemia (HC) increases amyloid-β (Aβ) accumulation and accelerates Alzheimer’s disease (AD) pathology. However, the association of HC with AD in human studies has not been consistently established. Objective: We aimed to investigate the relationship between HC and risk of AD neuropathology in a large national sample with autopsies. Methods: This study used neuropathological and clinical data from 3,508 subjects from the National Alzheimer’s Coordinating Center (NACC) who underwent autopsies from 2005 to 2017. Demographic and clinical characteristics, as well as neuropathological outcomes were compared between subjects with and without HC. Associations between HC and AD neuropathology were examined by multivariate ordinal logistic regressions adjusting for potential confounders. Results: HC was not associated with any AD neuropathology in a model only adjusting for demographic variables. However, HC was significantly associated with higher CERAD neuritic and diffuse plaque burden, higher Braak stage, and more severe cerebral amyloid angiopathy when analyzed in a multivariate model controlling for comorbidities. Additional adjusting for cerebrovascular conditions did not diminish these associations. The association between HC and increased risk of neuritic plaques weakened but remained significant even after controlling for ApoE genotype. Conclusion: This study suggested that HC was associated with increased severity of AD pathology, which could only be partially accounted for by ApoE genotype. The associations were not mediated by cerebrovascular conditions.
Confusion assessment method accurately screens for hepatic encephalopathy and predicts short‑term mortality in hospitalized patients with cirrhosis
(Springer, 2023) Desai, Archita P.; Gandhi, Devika; Xu, Chenjia; Ghabril, Marwan; Nephew, Lauren; Patidar, Kavish R.; Campbell, Noll L.; Chalasani, Naga; Orman, Eric S.; Medicine, School of Medicine
Hepatic encephalopathy (HE), a subtype of delirium, is common in cirrhosis and associated with poor outcomes. Yet, objective bedside screening tools for HE are lacking. We examined the relationship between an established screening tool for delirium, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and short-term outcomes while comparing its performance with previously established measures of cognitive function such as West Haven criteria (WHC). Prospectively enrolled adults with cirrhosis who completed the CAM-ICU from 6/2014-6/2018 were followed for 90 days. Blinded provider-assigned West Haven Criteria (WHC) and other measures of cognitive function were collected. Logistic regression was used to test associations between CAM-ICU status and outcomes. Mortality prediction by CAM-ICU status was assessed using Area under the Receiver Operating Characteristics curves (AUROC). Of 469 participants, 11% were CAM-ICU( +), 55% were male and 94% were White. Most patients were Childs-Pugh class C (59%). CAM-ICU had excellent agreement with WHC (Kappa = 0.79). CAM-ICU( +) participants had similar demographic features to those CAM-ICU(-), but had higher MELD (25 vs. 19, p < 0.0001), were more often admitted to the ICU (28% vs. 7%, p < 0.0001), and were more likely to be admitted for HE and infection. CAM-ICU( +) participants had higher mortality (inpatient:37% vs. 3%, 30-day:51% vs. 11%, 90-day:63% vs. 23%, p < 0.001). CAM-ICU status predicted mortality with AUROC of 0.85, 0.82 and 0.77 for inpatient, 30-day and 90-day mortality, respectively. CAM-ICU easily screens for delirium/HE, has excellent agreement with WHC, and identifies a hospitalized cirrhosis cohort with high short-term mortality.
Critical Care Recovery Center: a model of agile implementation in intensive care unit (ICU) survivors
(Cambridge University Press, 2020-12) Wang, Sophia; Hanneman, Philip; Xu, Chenjia; Gao, Sujuan; Allen, Duane; Golovyan, Dmitry; Kheir, You Na; Fowler, Nicole; Austrom, Mary; Khan, Sikandar; Boustani, Malaz; Khan, Babar; Psychiatry, School of Medicine
Background: As many as 70% of intensive care unit (ICU) survivors suffer from long-term physical, cognitive, and psychological impairments known as post-intensive care syndrome (PICS). We describe how the first ICU survivor clinic in the United States, the Critical Care Recovery Center (CCRC), was designed to address PICS using the principles of Agile Implementation (AI). Methods: The CCRC was designed using an eight-step process known as the AI Science Playbook. Patients who required mechanical ventilation or were delirious ≥48 hours during their ICU stay were enrolled in the CCRC. One hundred twenty subjects who completed baseline HABC-M CG assessments and had demographics collected were included in the analysis to identify baseline characteristics that correlated with higher HABC-M CG scores. A subset of patients and caregivers also participated in focus group interviews to describe their perceptions of PICS. Results: Quantitative analyses showed that the cognitive impairment was a major concern of caregivers. Focus group data also confirmed that caregivers of ICU survivors (n = 8) were more likely to perceive cognitive and mental health symptoms than ICU survivors (n = 10). Caregivers also described a need for ongoing psychoeducation about PICS, particularly cognitive and mental health symptoms, and for ongoing support from other caregivers with similar experiences. Conclusions: Our study demonstrated how the AI Science Playbook was used to build the first ICU survivor clinic in the United States. Caregivers of ICU survivors continue to struggle with PICS, particularly cognitive impairment, months to years after discharge. Future studies will need to examine whether the CCRC model of care can be adapted to other complex patient populations seen by health-care professionals.
Decreasing Delirium Through Music: A Randomized Pilot Trial
(American Association of Critical-Care Nurses, 2020-03-01) Khan, Sikandar H.; Xu, Chenjia; Purpura, Russell; Durrani, Sana; Lindroth, Heidi; Wang, Sophia; Gao, Sujuan; Heiderscheit, Annie; Chlan, Linda; Boustani, Malaz; Khan, Babar A.; Medicine, School of Medicine
Background: Management of delirium in intensive care units is challenging because effective therapies are lacking. Music is a promising nonpharmacological intervention. Objectives: To determine the feasibility and acceptability of personalized music (PM), slow-tempo music (STM), and attention control (AC) in patients receiving mechanical ventilation in an intensive care unit, and to estimate the effect of music on delirium. Methods: A randomized controlled trial was performed in an academic medical-surgical intensive care unit. After particular inclusion and exclusion criteria were applied, patients were randomized to groups listening to PM, relaxing STM, or an audiobook (AC group). Sessions lasted 1 hour and were given twice daily for up to 7 days. Patients wore noise-canceling headphones and used mp3 players to listen to their music/audiobook. Delirium and delirium severity were assessed twice daily by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the CAM-ICU-7, respectively. Results: Of the 1589 patients screened, 117 (7.4%) were eligible. Of those, 52 (44.4%) were randomized, with a recruitment rate of 5 patients per month. Adherence was higher in the groups listening to music (80% in the PM and STM groups vs 30% in the AC group; P = .01), and 80% of patients surveyed rated the music as enjoyable. The median number (interquartile range) of delirium/coma-free days by day 7 was 2 (1-6) for PM, 3 (1-6) for STM, and 2 (0-3) for AC (P = .32). Median delirium severity was 5.5 (1-7) for PM, 3.5 (0-7) for STM, and 4 (1-6.5) for AC (P = .78). Conclusions: Music delivery is acceptable to patients and is feasible in intensive care units. Further research testing use of this promising intervention to reduce delirium is warranted.
Development and Validation of a Model to Predict Acute Kidney Injury in Hospitalized Patients With Cirrhosis
(Wolters Kluwer, 2019-09) Patidar, Kavish R.; Xu, Chenjia; Shamseddeen, Hani; Cheng, Yao-Wen; Ghabril, Marwan S.; Mukthinuthalapati, V.V. Pavan K.; Fricker, Zachary P.; Akinyeye, Samuel; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of Medicine
OBJECTIVES: Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis which contributes to morbidity and mortality. Improved prediction of AKI in this population is needed for prevention and early intervention. We developed a model to identify hospitalized patients at risk for AKI. METHODS: Admission data from a prospective cohort of hospitalized patients with cirrhosis without AKI on admission (n = 397) was used for derivation. AKI development in the first week of admission was captured. Independent predictors of AKI on multivariate logistic regression were used to develop the prediction model. External validation was performed on a separate multicenter cohort (n = 308). RESULTS: In the derivation cohort, the mean age was 57 years, the Model for End-Stage Liver Disease score was 17, and 59 patients (15%) developed AKI after a median of 4 days. Admission creatinine (OR: 2.38 per 1 mg/dL increase [95% CI: 1.47-3.85]), international normalized ratio (OR: 1.92 per 1 unit increase [95% CI: 1.92-3.10]), and white blood cell count (OR: 1.09 per 1 × 10/L increase [95% CI: 1.04-1.15]) were independently associated with AKI. These variables were used to develop a prediction model (area underneath the receiver operator curve: 0.77 [95% CI: 0.70-0.83]). In the validation cohort (mean age of 53 years, Model for End-Stage Liver Disease score of 16, and AKI development of 13%), the area underneath the receiver operator curve for the model was 0.70 (95% CI: 0.61-0.78). DISCUSSION: A model consisting of admission creatinine, international normalized ratio, and white blood cell count can identify patients with cirrhosis at risk for in-hospital AKI development. On further validation, our model can be used to apply novel interventions to reduce the incidence of AKI among patients with cirrhosis who are hospitalized.
Effect of Delirium on Physical Function in Noncardiac Thoracic Surgery Patients
(American Association of Critical-Care Nurses, 2020-03) Khan, Sikandar H.; Xu, Chenjia; Wang, Sophia; Gao, Sujuan; Lasiter, Sue; Kesler, Kenneth; Khan, Babar A.; Medicine, School of Medicine
Background: The effect of delirium on physical function in patients undergoing noncardiac thoracic surgery has not been well described and may differ from that in other surgical populations. Objective: To determine the effects of delirium on muscle strength and functional independence. The primary end point was change in Medical Research Council sum score (MRC-SS) by delirium status. Methods: A secondary analysis of data from a clinical trial involving English-speaking adults aged 18 years or older who were undergoing major noncardiac thoracic surgery. Exclusion criteria were history of schizophrenia, Parkinson disease, dementia, alcohol abuse, or neuroleptic malignant syndrome; haloperidol allergy; being pregnant or nursing; QT prolongation; and taking levodopa or cholinesterase inhibitors. Delirium was assessed twice daily using the Confusion Assessment Method for the Intensive Care Unit. Preoperatively and postoperatively, muscle strength was assessed using the modified MRC-SS and functional independence was assessed using the Katz scale of activities of daily living. Changes in MRC-SS and Katz score by delirium status were analyzed using the Fisher exact test. Results: Seventy-three patients were included in the analysis. Median (interquartile range) MRC-SS and Katz score before surgery did not differ significantly between patients without and with delirium (MRC-SS: 30 [30-30] vs 30 [30-30], P > .99; Katz score: 6 [6-6] vs 6 [6-6], P = .63). The percentage of patients with a change in MRC-SS was similar in patients without and with delirium (17% vs 13%, respectively; P > .99). More patients in the delirium group had a change in Katz score (13% vs 0%, P = .04). Conclusions: Postoperative delirium was not associated with change in muscle strength. Follow-up studies using other muscle measures may be needed.
Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients with Cirrhosis: A Prospective Study
(Wolters Kluwer, 2020-09) Patidar, Kavish R.; Shamseddeen, Hani; Xu, Chenjia; Ghabril, Marwan S.; Nephew, Lauren D.; Desai, Archita P.; Anderson, Melissa; El-Achkar, Tarek M.; Ginès, Pere; Chalasani, Naga P.; Orman, Eric S.; Medicine, School of Medicine
Introduction: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study. Methods: Hospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. Results: H-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035). Discussion: Compared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.
Palliative Care, Patient-Reported Measures, and Outcomes in Hospitalized Patients with Cirrhosis
(Elsevier, 2022) Orman, Eric S.; Yousef, Andrew; Xu, Chenjia; Shamseddeen, Hani; Johnson, Amy W.; Nephew, Lauren; Ghabril, Marwan; Desai, Archita P.; Patidar, Kavish R.; Chalasani, Naga; Medicine, School of Medicine
Context: Studies of palliative care (PC) in hospitalized patients with cirrhosis have been retrospective, with limited evaluation of patient-reported measures and outcomes. Objectives: To examine the relationship between PC, patient-reported measures (quality of life and functional status), and outcomes. Methods: We performed a prospective cohort study of patients with cirrhosis hospitalized from 2014 to 2019. We recorded PC consultation details, quality of life (chronic liver disease questionnaire), and functional status (functional status questionnaire). Patients were followed for 90 days to assess readmissions, costs, and mortality. Results: Seventy-four of 679 patients saw PC, often later in the hospitalization (median hospital day 8; IQR 4-16). Those who saw PC had greater Charlson comorbidity index (mean 6.8 vs. 5.9), MELD (mean 25 vs. 20), and prior 30-day admission (47% vs. 35%). Compared to those who did not see PC, PC patients had greater impairments in intermediate activities of daily living (83% vs. 72%), social activity (72% vs. 59%), quality of interactions (49% vs. 36%), abdominal symptoms (mean score 3.1 vs. 3.6), activity (mean 3.3 vs. 3.6), and overall quality of life (mean 3.6 vs. 3.8). PC was associated with fewer transfusions and upper endoscopies and with greater completion of advanced directives. After multivariable adjustment, PC was not associated with intensive care, 30-day readmissions, 90-day costs, or mortality. Conclusion: PC occurs infrequently and late in those with more severe liver disease and functional impairment. PC may be associated with reduction in utilization and greater completion of advanced directives. Randomized trials are needed to evaluate PC for this population.
Patient-Reported Outcome Measures Modestly Enhance Prediction of Readmission in Patients with Cirrhosis
(Elsevier, 2021) Orman, Eric S.; Ghabril, Marwan S.; Desai, Archita P.; Nephew, Lauren; Patidar, Kavish R.; Gao, Sujuan; Xu, Chenjia; Chalasani, Naga; Medicine, School of Medicine
Background & Aims Patients with cirrhosis have high rates of hospital readmission, but prediction models are suboptimal and have not included important patient-reported outcome measures (PROMs). In a large prospective cohort, we examined the impact of PROMs on prediction of 30-day readmissions. Methods We performed a prospective cohort study of adults with cirrhosis admitted to a tertiary center between June 2014 and March 2020. We collected clinical information, socioeconomic status, and PROMs addressing functional status and quality of life. We used hierarchical competing risk time-to-event analysis to examine the impact of PROMs on readmission prediction. Results 654 patients were discharged alive, and 247 (38%) were readmitted within 30 days. Readmission was independently associated with cerebrovascular disease, ascites, prior hospital admission, admission via the emergency department, lower albumin, higher MELD, discharge with public transportation, and impaired basic activities of daily living and quality of life activity domain. Reduced readmission was associated with cancer, admission for infection, children at home, and impaired emotional function. Compared to a model including only clinical variables, addition of functional status and quality of life variables improved the area under the receiver operating characteristic curve (AUROC) from 0.72 to 0.73 and 0.75, with net reclassification indices of 0.22 and 0.18, respectively. Socioeconomic variables did not significantly improve prediction compared to clinical variables alone. Compared to a model using electronically-available variables only, no models improved prediction when examined with integrated discrimination improvement. Conclusions PROMs may marginally add to the prediction of 30-day readmissions for patients with cirrhosis. Poor social support and disability are associated with readmissions and may be high-yield targets for future interventions.

Browsing by Author "Xu, Chenjia"

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