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Item Age and comorbidity association with survival outcomes in metastatic colorectal cancer: CALGB 80405 analysis(Elsevier, 2022) McCleary, Nadine J.; Zhang, Sui; Ma, Chao; Ou, Fang-Shu; Bainter, Tiffany M.; Venook, Alan P.; Niedzwiecki, Donna; Lenz, Heinz-Josef; Innocenti, Federico; O'Neil, Bert H.; Polite, Blase N.; Hochster, Howard S.; Atkins, James N.; Goldberg, Richard M.; Ng, Kimmie; Mayer, Robert J.; Blanke, Charles D.; O'Reilly, Eileen M.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Medicine, School of MedicineBackground: Little is known about the interaction of comorbidities and age on survival outcomes in colorectal cancer (mCRC), nor how comorbidities impact treatment tolerance. Methods: We utilized a cohort of 1345 mCRC patients enrolled in CALGB/SWOG 80405, a multicenter phase III trial of fluorouracil/leucovorin + oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) plus bevacizumab, cetuximab or both. Endpoints were overall survival (OS), progression-free survival (PFS), and grade ≥ 3 toxicities assessed using NCI CTCAE v.3.0. Participants completed a questionnaire, including a modified Charlson Comorbidity Index. Adjusted Cox and logistic regression models tested associations of comorbidities and age on the endpoints. Results: In CALGB/SWOG 80405, 1095 (81%) subjects were < 70 years and >70 250 (19%). Presence of ≥1 comorbidity was not significantly associated with either OS (HR 1.10, 95% CI 0.96-1.25) or PFS (HR 1.03, 95% CI 0.91-1.16). Compared to subjects <70 with no comorbidities, OS was non-significantly inferior for ≥70 with no comorbidities (HR 1.21, 95% CI 0.98-1.49) and significantly inferior for ≥70 with at least one comorbidity (HR 1.51, 95% CI 1.22-1.86). There were no significant associations or interactions between age or comorbidity with PFS. Comorbidities were not associated with treatment-related toxicities. Age ≥ 70 was associated with greater risk of grade ≥ 3 toxicities (OR 2.15, 95% CI 1.50-3.09, p < 0.001). Conclusions: Among participants in a clinical trial of combination chemotherapy for mCRC, presence of older age with comorbidities was associated with worse OS but not PFS. The association of age with toxicity suggests additional factors of care should be measured in clinical trials.Item Clinical Characteristics of Non-Intensive Care Unit COVID-19 Patients in Saudi Arabia: A Descriptive Cross-sectional Study(Elsevier, 2020-11-13) Al-Omari, Awad; Alhuqbani, Waad N.; Zaidi, Abdul Rehman Z.; Al-Subaie, Maha F.; AlHindi, Alanoud M.; Abogosh, Ahmed K.; Alrasheed, Aljwhara K.; Alsharafi, Aya A.; Alhuqbani, Mohammed N.; Salih, Samer; Alhedaithy, Mogbil Abdullah; Abdulqawi, Rayid; Ismail, Alaa Fariz; Alhumaid, Saad; Hamdan, Noura; Saad, Fares; Olhaye, Fahad Abdullah; Eltahir, Tarig Ali; Alomari, Mohammed; Alshehery, Maied; Yassiri, Aziz; Al-Tawfiq, Jaffar A.; Al Mutair, Abbas; Medicine, School of MedicineIntroduction: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is a global health concern. It has affected more than 5 million patients worldwide and resulted in an alarming number of deaths globally. While clinical characteristics have been reported elsewhere, data from our region is scarce. We investigated the clinical characteristics of mild to moderate cases of COVID-19 in Saudi Arabia. Methods: This is a descriptive, cross-sectional study. Data of 401 confirmed COVID-19 patients were collected from 22 April 2020 to 21 May 2020 at five tertiary care hospitals in Riyadh, Saudi Arabia. The patients were divided into four groups according to age, Group 1: 0-<18 years, Group 2: 18-<50 years, Group 3: 50-60 years, and Group 4: >60 years; and their clinical symptoms were compared. Results: The median (IQR) age in years was 10.5 (1.5-16) in group I, 34 (29-41) in group II, 53 (51-56) in group III, and 66 (61-76) in group IV. Most patients were male (80%, n = 322) and of Arabian or Asian descent. The median length of stay in the hospital was 10 (8-17) days (range 3-42 days). The most common symptoms were cough (53.6%), fever (36.2%), fatigue (26.4%), dyspnea (21.9%), and sore throat (21.9%). Hypertension was the most common underlying comorbidity (14.7%), followed by obesity (11.5%), and diabetes (10%). Hypertensive patients were less likely to present with shortness of breath, cough, sputum, diarrhea, and fever. Conclusion: There was no significant difference in the symptoms among different age groups and comorbidities were mostly seen in the older age group. Interestingly, hypertensive patients were found to have milder symptoms and a shorter length of stay. Further larger collaborative national studies are required to effectively understand clinical characteristics in our part of the world to efficiently manage and control the spread of SARS-CoV-2.Item Comorbid Conditions Among Adults 50 Years and Older With Traumatic Brain Injury: Examining Associations With Demographics, Healthcare Utilization, Institutionalization, and 1-Year Outcomes(Wolters Kluwer, 2019) Kumar, Raj G.; Olsen, Jennifer; Juengst, Shannon B.; Dams-OʼConnor, Kristen; OʼNeil-Pirozzi, Therese M.; Hammond, Flora M.; Wagner, Amy K.; Physical Medicine and Rehabilitation, School of MedicineObjectives: To assess the relationship of acute complications, preexisting chronic diseases, and substance abuse with clinical and functional outcomes among adults 50 years and older with moderate-to-severe traumatic brain injury (TBI). Design: Prospective cohort study. Participants: Adults 50 years and older with moderate-to-severe TBI (n = 2134). Measures: Clusters of comorbid health conditions empirically derived from non-injury International Classification of Diseases, Ninth Revision codes, demographic/injury variables, and outcome (acute and rehabilitation length of stay [LOS], Functional Independence Measure efficiency, posttraumatic amnesia [PTA] duration, institutionalization, rehospitalization, and Glasgow Outcome Scale-Extended (GOS-E) at 1 year). Results: Individuals with greater acute hospital complication burden were more often middle-aged men, injured in motor vehicle accidents, and had longer LOS and PTA. These same individuals experienced higher rates of 1-year rehospitalization and greater odds of unfavorable GOS-E scores at 1 year. Those with greater chronic disease burden were more likely to be rehospitalized at 1 year. Individuals with more substance abuse burden were most often younger (eg, middle adulthood), black race, less educated, injured via motor vehicle accidents, and had an increased risk for institutionalization. Conclusion: Preexisting health conditions and acute complications contribute to TBI outcomes. This work provides a foundation to explore effects of comorbidity prevention and management on TBI recovery in older adults.Item Comorbidity, cognitive dysfunction, physical functioning, and quality of life in older breast cancer survivors(Springer, 2022-01) Crouch, Adele; Champion, Victoria L.; Von Ah, Diane; School of NursingPurpose: Older breast cancer survivors (BCS) may be at greater risk for cognitive dysfunction and other comorbidities; both of which may be associated with physical and emotional well-being. This study will seek to understand these relationships by examining the association between objective and subjective cognitive dysfunction and physical functioning and quality of life (QoL) and moderated by comorbidities in older BCS. Methods: A secondary data analysis was conducted on data from 335 BCS (stages I-IIIA) who were ≥ 60 years of age, received chemotherapy, and were 3-8 years post-diagnosis. BCS completed a one-time questionnaire and neuropsychological tests of learning, delayed recall, attention, working memory, and verbal fluency. Descriptive statistics and separate linear regression analyses testing the relationship of each cognitive assessment on physical functioning and QoL controlling for comorbidities were conducted. Results: BCS were on average 69.79 (SD = 3.34) years old and 5.95 (SD = 1.48) years post-diagnosis. Most were stage II (67.7%) at diagnosis, White (93.4%), had at least some college education (51.6%), and reported on average 3 (SD = 1.81) comorbidities. All 6 physical functioning models were significant (p < .001), with more comorbidities and worse subjective attention identified as significantly related to decreased physical functioning. One model found worse subjective attention was related to poorer QoL (p < .001). Objective cognitive function measures were not significantly related to physical functioning or QoL. Conclusions: A greater number of comorbidities and poorer subjective attention were related to poorer outcomes and should be integrated into research seeking to determine predictors of physical functioning and QoL in breast cancer survivors.Item Contemporary Trends in Hospitalizations for Comorbid Chronic Liver Disease and Substance Use Disorders(Wolters Kluwer, 2021-06-18) Desai, Archita P.; Greene, Marion; Nephew, Lauren D.; Orman, Eric S.; Ghabril, Marwan; Chalasani, Naga; Menachemi, Nir; Medicine, School of MedicineIntroduction: Chronic liver diseases (CLDs) and substance use disorders (SUDs) are increasingly prevalent and often coexist. Contemporary studies describing the characteristics and hospitalization trends of those with comorbid CLD-SUD are lacking. We aimed to characterize a population-based cohort with comorbid CLD-SUD and describe trends in these hospitalizations over time by individual-level characteristics. Methods: We performed a cross-sectional analysis of the National Inpatient Sample from 2005 through 2017. Diagnosis codes were used to identify adult hospitalizations with CLD, SUD, or both. Bivariate and multivariate analyses were used to make comparisons between diagnosis categories. Unadjusted and age-adjusted trends in these hospitalizations were described over time. Results: Of 401,867,749 adult hospital discharges, 3.2% had CLD-only and 1.7% had comorbid CLD-SUD. Compared with CLD-only, comorbid CLD-SUD hospitalizations resulted in higher inpatient mortality (3.1% vs 2.4%, P < 0.001) and were associated with younger age, male sex, Native American race, and urban and Western US location. Over time, comorbid hospitalizations grew 34%, and the demographics shifted with larger increases in hospitalization rates seen in younger individuals, women, Native Americans, and those publicly insured. In comorbid hospitalizations, alcoholic SUD and CLD decreased, but drug SUDs and nonalcoholic fatty liver diseases are fast-growing contributors. Discussion: In this comprehensive analysis of US hospitalizations, comorbid CLD-SUD hospitalizations are increasing over time and lead to higher inpatient mortality than CLD alone. We further characterize the changing demographics of these hospitalizations, providing a contemporary yet inclusive look at comorbid CLD-SUD hospitalizations. These data can guide interventions needed to improve the poor outcomes suffered by this growing population.Item Contraceptive Preference, Continuation Rates, and Unintended Pregnancies in Patients with Comorbidities: A Prospective Cohort Study(Mary Ann Liebert, 2021) Leroy-Melamed, Maayan; Zhao, Qiuhong; Belmonte, Michael A.; Archer, Johanna; Peipert, Jeffrey F.; Pediatrics, School of MedicineBackground: Patients with comorbidities are more susceptible to adverse pregnancy outcomes, morbidity, and mortality than healthy patients. The goal of this study was to evaluate how comorbidities influence contraceptive choice, continuation rates, and the unintended pregnancy rate in reproductive-age participants. Methods: We analyzed data from the Contraceptive CHOICE Project. Baseline data included demographic, reproductive, and medical history, including self-reported hypertension (HTN), venous thromboembolism (VTE), migraines, cerebrovascular accidents (CVA), transient ischemic attack (TIA), or stroke. Participants were provided contraceptive counseling and their method of choice at no cost. Results: Among 9253 participants included in our analysis, 659 participants reported a history of HTN (7%), 20 participants reported a history of CVA/TIA/stroke (<1%), 1803 participants reported a history of migraine (19%), and 85 reported a history of VTE (<1%). Compared to baseline, use of long-acting reversible contraceptive methods (long-acting reversible contraception [LARC]: intrauterine devices and implants) increased for participants with all comorbidities: HTN 2.3%–84.2%; CVA/TIA/stroke 0%–85%; migraines 1.7%–77%, and VTE 1.2%–88.2%. Participants with HTN, VTE, and migraines were more likely to choose LARC than those without those conditions: HTN: relative risk (RR) = 1.14, 95% confidence interval (CI) 1.10–1.18; migraines RR = 1.04, 95% CI 1.01–1.07; and VTE RR = 1.18, 95% CI 1.09–1.28. Twelve-month continuation and unintended pregnancy rates did not differ significantly based on comorbidity status. Conclusions: Participants with serious comorbidities were more likely to choose LARC than healthy participants. Contraceptive counseling should always be individualized to the patient.Item Contribution of Behavioral Health Factors to Non-AIDS-Related Comorbidities: an Updated Review(SpringerLink, 2020-08) Chichetto, Natalie E.; Polanka, Brittanny M.; So-Armah, Kaku A.; Sung, Minhee; Stewart, Jesse C.; Koethe, John R.; Edelman, E. Jennifer; Tindle, Hilary A.; Freiberg, Matthew S.; Psychology, School of SciencePurpose of review: We summarize recent literature on the contribution of substance use and depression to non-AIDS-related comorbidities. Discussion of recent randomized clinical trials and implementation research to curtail risk attributed to each behavioral health issue is provided. Recent findings: Smoking, unhealthy alcohol use, opioid use, and depression are common among PWH and individually contribute to increased risk for non-AIDS-related comorbidities. The concurrence of these conditions is notable, yet understudied, and provides opportunity for linked-screening and potential treatment of more than one behavioral health factor. Current results from randomized clinical trials are inconsistent. Investigating interventions to reduce the impact of these behavioral health conditions with a focus on implementation into clinical care is important. Non-AIDS-defining cancers, cardiovascular disease, liver disease, and diabetes are leading causes of morbidity in people with HIV. Behavioral health factors including substance use and mental health issues, often co-occurring, likely contribute to the excess risk of non-AIDS-related comorbidities.Item Depression and Anxiety Screens as Simultaneous Predictors of 10-Year Incidence of Diabetes Mellitus in Older Adults in Primary Care(Wiley, 2017-02) Khambaty, Tasneem; Callahan, Christopher M.; Perkins, Anthony J.; Stewart, Jesse C.; Medicine, School of MedicineOBJECTIVES: To examine depression and anxiety screens and their individual items as simultaneous predictors of incident diabetes mellitus. DESIGN: Ten-year follow-up study of individuals screened for the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. SETTING: Two large urban primary care clinics in Indianapolis, Indiana. PARTICIPANTS: Diverse sample (53% African American, 80% of lower socioeconomic status) of 2,156 older adults initially free of diabetes mellitus. MEASUREMENTS: Depression and anxiety screens were completed during routine primary care visits between 1999 and 2001. Incident diabetes mellitus data were obtained from an electronic medical record system and the Centers for Medicare and Medicaid Services analytical files though 2009. RESULTS: Over the 10-year period, 558 (25.9%) participants had diabetes mellitus onset. Cox proportional hazards models adjusted for demographic and diabetes mellitus risk factors revealed that a positive screen for anxiety, but not for depression, predicted incident diabetes mellitus when entered into separate models (anxiety: hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.15-1.61, P < .001; depression: HR = 1.18, 95% CI = 0.95-1.46, P = .13) and when entered simultaneously into one model (anxiety: HR = 1.35, 95% CI = 1.12-1.61, P < .001; depression: HR = 1.04, 95% CI = 0.83-1.31, P = .73). The feeling anxious (P = .03) and the worry (P = .02) items predicted incident diabetes mellitus independent of the depression screen. CONCLUSION: These findings suggest that screening positive for anxiety is a risk factor for diabetes mellitus in older adults independent of depression and traditional diabetes mellitus risk factors. Anxiety requires greater consideration and awareness in the context of diabetes mellitus risk assessment and primary prevention.Item Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome(Elsevier, 2017-02) Szilágyi, Keely L.; Liu, Cong; Zhang, Xu; Wang, Ting; Fortman, Jeffrey D.; Zhang, Wei; Garcia, Joe G.N.; Medicine, School of MedicineAcute respiratory distress syndrome (ARDS) is a devastating clinical syndrome with a considerable case fatality rate (∼30%-40%). Health disparities exist with African descent (AD) subjects exhibiting greater mortality than European descent (ED) individuals. Myosin light chain kinase is encoded by MYLK, whose genetic variants are implicated in ARDS pathogenesis and may influence ARDS mortality. As baseline population-specific epigenetic changes, that is, cytosine modifications, have been observed between AD and ED individuals, epigenetic variations in MYLK may provide insights into ARDS disparities. We compared methylation levels of MYLK cytosine-guanine dinucleotides (CpGs) between ARDS patients and intensive care unit (ICU) controls overall and by ethnicity in a nested case-control study of 39 ARDS cases and 75 non-ARDS ICU controls. Two MYLK CpG sites (cg03892735 and cg23344121) were differentially modified between ARDS subjects and controls (P < 0.05; q < 0.25) in a logistic regression model, where no effect modification by ethnicity or age was found. One CpG site was associated with ARDS in patients aged <58 years, cg19611163 (intron 19, 20). Two CpG sites were associated with ARDS in EDs only, gene body CpG (cg01894985, intron 2, 3) and CpG (cg16212219, intron 31, 32), with higher modification levels exhibited in ARDS subjects than controls. Cis-acting modified cytosine quantitative trait loci (mQTL) were identified using linear regression between local genetic variants and modification levels for 2 ARDS-associated CpGs (cg23344121 and cg16212219). In summary, these ARDS-associated MYLK CpGs with effect modification by ethnicity and local mQTL suggest that MYLK epigenetic variation and local genetic background may contribute to health disparities observed in ARDS.Item Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease(BMC, 2020-09-16) Coppel, Scott; Mathur, Karan; Ekser, Burcin; Patidar, Kavish R.; Orman, Eric; Desai, Archita P.; Vilar-Gomez, Eduardo; Kubal, Chandrashekhar; Chalasani, Naga; Nephew, Lauren; Ghabril, Marwan; Medicine, School of MedicineBackground We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT). Methods Adults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortality (competing risk analysis). Results The study included 340 patients, mean age 56 ± 11, 63% male and MELD-Na 17.2 ± 6.6. The CCI was 0 (no comorbidities) in 44%, 1–2 in 44% and > 2 (highest decile) in 12%, with no differences based on gender but higher CCI in patients with fatty and cryptogenic liver disease. Thirty-three (10%) of 332 patients not receiving LT within 90 days died. Beyond MELD-Na, the CCI was independently associated with 90-day mortality (hazard ratio (HR), 1.32 (95% confidence interval (CI) 1.02–1.72). Ninety-day mortality was specifically increased with higher CCI category and MELD ≥18 (12% (CCI = 0), 22% (CCI = 1–2) and 33% (CCI > 2), (p = 0.002)) but not MELD-Na ≤17. At last follow-up, 69 patients were alive, 100 underwent LT and 171 died without LT. CCI was associated with increased overall mortality in the competing risk analysis (Sub-HR 1.24, 95%CI 1.1–1.4). Conclusions Extra-hepatic comorbidity burden significantly impacts short-term mortality in patients with cirrhosis and high MELD-Na. This has implications in determining urgency of LT and mortality models in cirrhosis and LT waitlisting, especially with an ageing population with increasing prevalence of fatty liver disease.
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