Browsing by Subject "Outcomes research"
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Item Artificial intelligence reveals features associated with breast cancer neoadjuvant chemotherapy responses from multi-stain histopathologic images(Springer Nature, 2023-01-27) Huang, Zhi; Shao, Wei; Han, Zhi; Alkashash, Ahmad Mahmoud; De la Sancha, Carlo; Parwani, Anil V.; Nitta, Hiroaki; Hou, Yanjun; Wang, Tongxin; Salama, Paul; Rizkalla, Maher; Zhang, Jie; Huang, Kun; Li, Zaibo; Electrical and Computer Engineering, School of Engineering and TechnologyAdvances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype.Item Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer(Springer Nature, 2021) Hussain, Arif; Tripathi, Abhishek; Pieczonka, Christopher; Cope, Diane; McNatty, Andrea; Logothetis, Christopher; Guise, Theresa; Medicine, School of MedicineBackground: Osteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment. Methods: We searched peer-reviewed literature on the PubMed database using key words "androgen-deprivation therapy," "androgen receptor inhibitors," "bone," "bone complications," and "nonmetastatic prostate cancer" from 2000 to present. Results: We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health. Conclusions: In patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.Item Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial(Wiley, 2016-07) Pun, Patrick H.; Abdalla, Safa; Block, Geoffrey A.; Chertow, Glenn M.; Correa-Rotter, Ricardo; Dehmel, Bastian; Drüeke, Tilman B.; Floege, Jürgen; Goodman, William G.; Herzog, Charles A.; London, Gerard M.; Mahaffey, Kenneth W.; Moe, Sharon M.; Parfrey, Patrick S.; Wheeler, David C.; Middleton, John P.; Medicine, School of MedicineAmong patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.Item Delirium severity does not differ between medical and surgical intensive care units after adjusting for medication use(Springer Nature, 2022-08-24) Ortiz, Damaris; Lindroth, Heidi L.; Braly, Tyler; Perkins, Anthony J.; Mohanty, Sanjay; Meagher, Ashley D.; Khan, Sikandar H.; Boustani, Malaz A.; Khan, Babar A.; Surgery, School of MedicineSevere delirium is associated with an increased risk of mortality, institutionalization, and length of stay. Few studies have examined differences in delirium severity between different populations of critically ill patients. The objective of the study was to compare delirium severity and the presence of the four core features between adults in the surgical intensive care unit (SICU) and medical intensive care unit (MICU) while controlling for variables known to be associated with delirium. This is a secondary analysis of two parallel randomized multi-center trials conducted from March 2009 to January 2015 at 3 Indianapolis hospitals. A total of 474 adults with delirium were included in the analysis. Subjects were randomized in a 1:1 ratio in random blocks of 4 by a computer program. Patients were randomized to either haloperidol prescribing or de-prescribing regimen vs usual care. Delirium severity was assessed daily or twice-daily using the CAM-ICU-7 beginning after 24 h of ICU admission and until discharge from the hospital, death, or 30 days after enrollment. Secondary outcomes included hospital length of stay, hospital and 30-day mortality, and delirium-related adverse events. These outcomes were compared between SICU and MICU settings for this secondary analysis. Out of 474 patients, 237 were randomized to intervention. At study enrollment, the overall cohort had a mean age of 59 (SD 16) years old, was 54% female, 44% African-American, and 81% were mechanically ventilated upon enrollment. MICU participants were significantly older and severely ill with a higher premorbid cognitive and physical dysfunction burden. In univariate analysis, SICU participants had significantly higher mean total CAM-ICU-7 scores, corresponding to delirium severity, (4.15 (2.20) vs 3.60 (2.32), p = 0.02), and a lower mean RASS score (- 1.79 (1.28) vs - 1.53 (1.27), p < 0.001) compared to MICU participants. Following adjustment for benzodiazepines and opioids, delirium severity did not significantly differ between groups. The presence of Feature 3, altered level of consciousness, was significantly associated with the SICU participants, identifying as Black, premorbid functional impairment, benzodiazepines, opioids, and dexmedetomidine. In this secondary analysis examining differences in delirium severity between MICU and SICU participants, we did not identify a difference between participant populations following adjustment for administered benzodiazepines and opioids. We did identify that an altered level of consciousness, core feature 3 of delirium, was associated with SICU setting, identifying as Black, activities of daily living, benzodiazepines and opioid medications. These results suggest that sedation practice patterns play a bigger role in delirium severity than the underlying physiologic insult, and expression of core features of delirium may vary based on individual factors.Item Functional outcome following inpatient rehabilitation among individuals with complete spinal cord injury in Nepal(Springer Nature, 2021-10-07) Khatri, Prakriti; Jalayondeja, Chutima; Dhakal, Raju; Groves, Christine C.; Physical Medicine and Rehabilitation, School of MedicineObjectives: To describe functional outcomes using Spinal Cord Independence Measure III (SCIM III) following inpatient rehabilitation among individuals with complete spinal cord injury (SCI) in the low-income setting of Nepal; to evaluate functional changes from rehabilitation admission to discharge and to compare functional outcomes between neurological levels of injury (NLI) at discharge. Setting: Spinal Injury Rehabilitation Centre (SIRC), Kavrepalanchowk, Nepal. Methods: We present data of all individuals with complete SCI who completed rehabilitation at SIRC in 2017. Data collected included: demographics, aetiology, neurological assessment, admission/discharge SCIM III scores, and length of stay. Data were analyzed using descriptive statistics. Pre/post-SCIM III scores were analyzed using Related-Samples Wilcoxon signed-rank test. Comparative analysis between NLIs was done using the Kruskal Wallis ANOVA test followed by pairwise Mann-Whitney U tests. Results: Ninety-six individuals were included. Mean (SD) age was 33.5 (14.2) years, with a male/female ratio of 3.4:1. Median admission and discharge total SCIM III scores for cervical, thoracic and lumbosacral levels were 10 and 21, 16 and 61, and 41 and 79.5, respectively. Median total SCIM III score change between admission and discharge were 11 (p = 0.003), 43 (p < 0.001) and 40 (p = 0.068) for cervical, thoracic and lumbar groups, respectively. Conclusions: This study is the first of its kind to describe functional outcomes among individuals with complete SCI in the low-income setting of Nepal. All SCI groups showed a positive trend in SCIM III from admission to discharge, with improvements reaching statistical significance among groups with cervical and thoracic NLIs.Item Medical and surgical interventions and outcomes for infants with trisomy 18 (T18) or trisomy 13 (T13) at children's hospitals neonatal intensive care units (NICUs)(Springer Nature, 2021) Acharya, Krishna; Leuthner, Steven R.; Zaniletti, Isabella; Niehaus, Jason Z.; Bishop, Christine E.; Coghill, Carl H.; Datta, Ankur; Dereddy, Narendra; DiGeronimo, Robert; Jackson, Laura; Ling, Con Yee; Matoba, Nana; Natarajan, Girija; Pritha Nayak, Sujir; Brown Schlegel, Amy; Seale, Jamie; Shah, Anita; Weiner, Julie; Williams, Helen O.; Wojcik, Monica H.; Fry, Jessica T.; Sullivan, Kevin; Palliative Care and Ethics Focus Group of the Children’s Hospital Neonatal Consortium (CHNC); Pediatrics, School of MedicineObjectives: To examine characteristics and outcomes of T18 and T13 infants receiving intensive surgical and medical treatment compared to those receiving non-intensive treatment in NICUs. Study design: Retrospective cohort of infants in the Children's Hospitals National Consortium (CHNC) from 2010 to 2016 categorized into three groups by treatment received: surgical, intensive medical, or non-intensive. Results: Among 467 infants admitted, 62% received intensive medical treatment; 27% received surgical treatment. The most common surgery was a gastrostomy tube. Survival in infants who received surgeries was 51%; intensive medical treatment was 30%, and non-intensive treatment was 72%. Infants receiving surgeries spent more time in the NICU and were more likely to receive oxygen and feeding support at discharge. Conclusions: Infants with T13 or T18 at CHNC NICUs represent a select group for whom parents may have desired more intensive treatment. Survival to NICU discharge was possible, and surviving infants had a longer hospital stay and needed more discharge supports.Item Monotherapy Anticoagulation to Expedite Home Treatment of Patients Diagnosed With Venous Thromboembolism in the Emergency Department: A Pragmatic Effectiveness Trial(American Heart Association, 2021) Kline, Jeffrey A.; Adler, David H.; Alanis, Naomi; Bledsoe, Joseph R.; Courtney, Daniel M.; d’Etienne, James P.; Diercks, Deborah B.; Garrett, John S.; Jones, Alan E.; Mackenzie, David C.; Madsen, Troy; Matuskowitz, Andrew J.; Mumma, Bryn E.; Nordenholz, Kristen E.; Pagenhardt, Justine; Runyon, Michael S.; Stubblefield, William B.; Willoughby, Christopher B.; Emergency Medicine, School of MedicineBackground: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. Methods: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. Results: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%-1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%-0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. Conclusions: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE.Item Participant-reported personal utility of genetic testing for Parkinson's disease and interest in clinical trial participation(Springer Nature, 2024-10-25) Oas, Hannah; Cook, Lola; Schwantes-An, Tae-Hwi; Walsh, Laurence E.; Wills, Anne-Marie; Mata, Ignacio F.; Nance, Martha A.; Beck, James C.; Naito, Anna; Marder, Karen; Alcalay, Roy N.; Verbrugge, Jennifer; Medical and Molecular Genetics, School of MedicineGenetic testing for Parkinson's disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants (n = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies. Most participants found their genetic test results useful, including satisfying curiosity (81%), feeling good about helping the medical community (80%), and having information to share with family (77%). There were no significant differences in responses based on result type. Forty-five percent of participants expressed interest in participating in research studies; whereas 16% of participants confirmed enrollment. Our results suggest that participants find personal utility in genetic testing regardless of results. Although participants may be interested in enrolling in additional research, they may need support and resources.Item Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner(Springer Nature, 2020-12) Li, Jie; Li, Xinle; Liu, Daquan; Zhang, Shiqi; Tan, Nian; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, School of Engineering and TechnologyNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.Item Preoperative stroke before cardiac surgery does not increase risk of postoperative stroke(Springer Nature, 2021-04-27) Matthews, Caleb R.; Hartman, Timothy; Madison, Mackenzie; Villelli, Nicolas W.; Namburi, Niharika; Colgate, Cameron L.; Faiza, Zainab; Lee, Lawrence S.; Medicine, School of MedicineThe optimal time when surgery can be safely performed after stroke is unknown. The purpose of this study was to investigate how cardiac surgery timing after stroke impacts postoperative outcomes between 2011–2017 were reviewed. Variables were extracted from the institutional Society of Thoracic Surgeons database, statewide patient registry, and medical records. Subjects were classified based upon presence of endocarditis and further grouped by timing of preoperative stroke relative to cardiac surgery: Recent (stroke within two weeks before surgery), Intermediate (between two and six weeks before), and Remote (greater than six weeks before). Postoperative outcomes were compared amongst groups. 157 patients were included: 54 in endocarditis and 103 in non-endocarditis, with 47 in Recent, 26 in Intermediate, and 84 in Remote. 30-day mortality and postoperative stroke rate were similar across the three subgroups for both endocarditis and non-endocarditis. Of patients with postoperative stroke, mortality was 30% (95% CI 4.6–66). Timing of cardiac surgery after stroke occurrence does not seem to affect postoperative stroke or mortality. If postoperative stroke does occur, subsequent stroke-related mortality is high.