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Assessing Risk Factors for Development of Immune-Mediated Diarrhea and Colitis During Immune Checkpoint-Inhibitor Therapy: A Real-World Data Analysis
Assessing Risk Factors for Development of Immune-Mediated Diarrhea and Colitis During Immu...
Assessing Risk Factors for Development of Immune-Mediated Diarrhea and Colitis During Immune Checkpoint-Inhibitor Therapy: A Real-World Data Analysis

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자료유형  
 학위논문 서양
최종처리일시  
20260202103037
ISBN  
9798293832576
DDC  
610.73
저자명  
Alekhina, Natalya.
서명/저자  
Assessing Risk Factors for Development of Immune-Mediated Diarrhea and Colitis During Immune Checkpoint-Inhibitor Therapy: A Real-World Data Analysis
발행사항  
[Sl] : The University of Utah, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
140 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
주기사항  
Advisor: Mooney, B. Kathleen.
학위논문주기  
Thesis (D.Phil.)--The University of Utah, 2025.
초록/해제  
요약Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse event (irAE) among patients receiving immune checkpoint inhibitors (ICIs), significantly affecting quality of life and treatment outcomes. However, its risk factors remain poorly understood, and large cohort studies defining a comprehensive risk phenotype are lacking. This dissertation investigated IMDC risk factors using three distinct approaches: (1) developing and testing a clinically grounded algorithm for identifying irAEs in structured real-world data, (2) applying the algorithm to identify key IMDC predictors, and (3) reviewing unstructured electronic health record (EHR) data to enhance the granularity of IMDC risk phenotype and assess real-world IMDC management and its alignment with clinical guidelines.Among 14,659 patients, 576 (3.93%) had moderate-severe irAEs, including 58 (0.40%) with IMDC. Compared to controls without irAEs, IMDC cases were more likely to be older ( 80 years, OR = 18.10, 95% CI = 2.11-155.47, p = 0.008) and obese (OR = 4.80, 95% CI = 1.29-17.93, p = 0.019). Notably, 62.07% and 55.17% of cases but only 1.48% and 2.96% of controls had received pain agents (OR = 57.90, 95% CI = 8.79-381.28, p 0.001) and anti-infective medications (OR = 415.32, 95% CI = 20.45-8434.61, p 0.001), yielding wide confidence intervals and inflated odds ratios, likely reflecting confounding or systematic bias in medication documentation.EHR review revealed significant variability in IMDC diagnosis and management, with Emergency Department practitioners adhering more closely to clinical guidelines than outpatient oncology clinicians. Seven of 17 patients with IMDC delayed seeking care for over a week, and 41.18% had concurrent irAEs.These findings suggest older, obese patients may be at increased IMDC risk, while medication-related associations warrant cautious interpretation and further investigation. The study underscores the need for proactive risk-mitigation strategies, including patient education and close monitoring. Future research incorporating diagnostic markers, prospective study design, and larger cohorts can refine IMDC risk phenotype and further explore deviations from clinical guidelines for timely diagnosis and management of IMDC.
일반주제명  
Nursing
일반주제명  
Oncology
일반주제명  
Immunology
키워드  
Immune-mediated diarrhea and colitis
키워드  
Immune-related adverse events
키워드  
Real-world data analysis
키워드  
Risk phenotype
기타저자  
The University of Utah Nursing
기본자료저록  
Dissertations Abstracts International. 87-03B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aAlekhina,  Natalya.
■24510▼aAssessing  Risk  Factors  for  Development  of  Immune-Mediated  Diarrhea  and  Colitis  During  Immune  Checkpoint-Inhibitor  Therapy:  A  Real-World  Data  Analysis
■260    ▼a[Sl]▼bThe  University  of  Utah▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a140  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-03,  Section:  B.
■500    ▼aAdvisor:  Mooney,  B.  Kathleen.
■5021  ▼aThesis  (D.Phil.)--The  University  of  Utah,  2025.
■520    ▼aImmune-mediated  diarrhea  and  colitis  (IMDC)  is  a  common  immune-related  adverse  event  (irAE)  among  patients  receiving  immune  checkpoint  inhibitors  (ICIs),  significantly  affecting  quality  of  life  and  treatment  outcomes.  However,  its  risk  factors  remain  poorly  understood,  and  large  cohort  studies  defining  a  comprehensive  risk  phenotype  are  lacking.  This  dissertation  investigated  IMDC  risk  factors  using  three  distinct  approaches:  (1)  developing  and  testing  a  clinically  grounded  algorithm  for  identifying  irAEs  in  structured  real-world  data,  (2)  applying  the  algorithm  to  identify  key  IMDC  predictors,  and  (3)  reviewing  unstructured  electronic  health  record  (EHR)  data  to  enhance  the  granularity  of  IMDC  risk  phenotype  and  assess  real-world  IMDC  management  and  its  alignment  with  clinical  guidelines.Among  14,659  patients,  576  (3.93%)  had  moderate-severe  irAEs,  including  58  (0.40%)  with  IMDC.  Compared  to  controls  without  irAEs,  IMDC  cases  were  more  likely  to  be  older  (  80  years,  OR  =  18.10,  95%  CI  =  2.11-155.47,  p  =  0.008)  and  obese  (OR  =  4.80,  95%  CI  =  1.29-17.93,  p  =  0.019).  Notably,  62.07%  and  55.17%  of  cases  but  only  1.48%  and  2.96%  of  controls  had  received  pain  agents  (OR  =  57.90,  95%  CI  =  8.79-381.28,  p    0.001)  and  anti-infective  medications  (OR  =  415.32,  95%  CI  =  20.45-8434.61,  p    0.001),  yielding  wide  confidence  intervals  and  inflated  odds  ratios,  likely  reflecting  confounding  or  systematic  bias  in  medication  documentation.EHR  review  revealed  significant  variability  in  IMDC  diagnosis  and  management,  with  Emergency  Department  practitioners  adhering  more  closely  to  clinical  guidelines  than  outpatient  oncology  clinicians.  Seven  of  17  patients  with  IMDC  delayed  seeking  care  for  over  a  week,  and  41.18%  had  concurrent  irAEs.These  findings  suggest  older,  obese  patients  may  be  at  increased  IMDC  risk,  while  medication-related  associations  warrant  cautious  interpretation  and  further  investigation.  The  study  underscores  the  need  for  proactive  risk-mitigation  strategies,  including  patient  education  and  close  monitoring.  Future  research  incorporating  diagnostic  markers,  prospective  study  design,  and  larger  cohorts  can  refine  IMDC  risk  phenotype  and  further  explore  deviations  from  clinical  guidelines  for  timely  diagnosis  and  management  of  IMDC.
■590    ▼aSchool  code:  0240.
■650  4▼aNursing
■650  4▼aOncology
■650  4▼aImmunology
■653    ▼aImmune-mediated  diarrhea  and  colitis
■653    ▼aImmune-related  adverse  events
■653    ▼aReal-world  data  analysis
■653    ▼aRisk  phenotype
■690    ▼a0569
■690    ▼a0992
■690    ▼a0982
■71020▼aThe  University  of  Utah▼bNursing.
■7730  ▼tDissertations  Abstracts  International▼g87-03B.
■790    ▼a0240
■791    ▼aD.Phil.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356801▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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