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Item 237. A Case-Control Study Investigating Household, Community, and Clinical Risk Factors Associated with Multisystem Inflammatory Syndrome in Children (MIS-C) after SARS-CoV-2 Infection(Oxford University Press, 2022) Zambrano, Laura D.; Wu, Michael J.; Martin, Lora M.; Malloch, Lacy; Newhams, Margaret M.; Son, Mary Beth; Sanders, Cameron; Patterson, Kayla; Halasa, Natasha B.; Fitzgerald, Julie C.; Leroue, Matthew; Hall, Mark; Irby, Katherine; Rowan, Courtney M.; Wellnitz, Kari; Loftis, Laura L.; Bradford, Tamara T.; Staat, Mary A.; Babbit, Christopher; Carroll, Christopher L.; Pannaraj, Pia S.; Kong, Michele; Chou, Janet; Patel, Manish M.; Randolph, Adrienne G.; Campbell, Angela P.; Hobbs, Charlotte V.; Medicine, School of MedicineBackground: Risk factors for MIS-C, a rare but serious hyperinflammatory syndrome associated with SARS-CoV-2 infection, remain unclear. We evaluated household, clinical, and environmental risk factors potentially associated with MIS-C. Methods: This investigation included MIS-C cases hospitalized in 14 US pediatric hospitals in 2021. Outpatient controls were frequency-matched to case-patients by age group and site and had a positive SARS-CoV-2 viral test within 3 months of the admission of their matched MIS-C case (Figure 1). We conducted telephone surveys with caregivers and evaluated potential risk factors using mixed effects multivariable logistic regression, including site as a random effect. We queried regarding exposures within the month before hospitalization for MIS-C cases or the month after a positive COVID-19 test for controls. Enrollment scheme for MIS-C case-patients and SARS-CoV-2-positive outpatient controls. MIS-C case-patients were identified through hospital electronic medical records, while two outpatient controls per case were identified through registries of outpatient SARS-CoV-2 testing logs at facilities affiliated with that medical center. Caregivers of outpatient controls were interviewed at least four weeks after their positive test to ensure they did not develop MIS-C after their infection. Results: We compared 275 MIS-C case-patients with 494 outpatient SARS-CoV-2-positive controls. Race, ethnicity and social vulnerability indices were similar. MIS-C was more likely among persons who resided in households with >1 resident per room (aOR=1.6, 95% CI: 1.1–2.2), attended a large (≥10 people) event with little to no mask-wearing (aOR=2.2, 95% CI: 1.4–3.5), used public transportation (aOR=1.6, 95% CI: 1.2–2.1), attended school >2 days per week with little to no mask wearing (aOR=2.1, 95% CI: 1.0–4.4), or had a household member test positive for COVID-19 (aOR=2.1, 95% CI: 1.3–3.3). MIS-C was less likely among children with comorbidities (aOR=0.5, 95% CI: 0.3–0.9) and in those who had >1 positive SARS-CoV-2 test at least 1 month apart (aOR=0.4, 95% CI: 0.2–0.6). MIS-C was not associated with a medical history of recurrent infections or family history of underlying rheumatologic disease. Conclusion: Household crowding, limited masking at large indoor events or schools and use of public transportation were associated with increased likelihood of developing MIS-C after SARS-CoV-2 infection. In contrast, decreased likelihood of MIS-C was associated with having >1 SARS-CoV-2 positive test separated by at least a month. Our data suggest that additional studies are needed to determine if viral load, and/or recurrent infections in the month prior to MIS-C contribute to MIS-C risk. Medical and family history were not associated with MIS-C in our analysis.Item Active Tuberculosis Is Associated with Worse Clinical Outcomes in HIV-Infected African Patients on Antiretroviral Therapy(Public Library of Science, 2013) Siika, Abraham M.; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara K.; Musick, Beverly S.; Mwangi, Ann W.; Diero, Lameck O.; Kimaiyo, Sylvester N.; Tierney, William M.; Carter, Jane E.; Medicine, School of MedicineObjective: This cohort study utilized data from a large HIV treatment program in western Kenya to describe the impact of active tuberculosis (TB) on clinical outcomes among African patients on antiretroviral therapy (ART). Design: We included all patients initiating ART between March 2004 and November 2007. Clinical (signs and symptoms), radiological (chest radiographs) and laboratory (mycobacterial smears, culture and tissue histology) criteria were used to record the diagnosis of TB disease in the program's electronic medical record system. Methods: We assessed the impact of TB disease on mortality, loss to follow-up (LTFU) and incident AIDS-defining events (ADEs) through Cox models and CD4 cell and weight response to ART by non-linear mixed models. Results: We studied 21,242 patients initiating ART-5,186 (24%) with TB; 62% female; median age 37 years. There were proportionately more men in the active TB (46%) than in the non-TB (35%) group. Adjusting for baseline HIV-disease severity, TB patients were more likely to die (hazard ratio--HR = 1.32, 95% CI 1.18-1.47) or have incident ADEs (HR = 1.31, 95% CI: 1.19-1.45). They had lower median CD4 cell counts (77 versus 109), weight (52.5 versus 55.0 kg) and higher ADE risk at baseline (CD4-adjusted odds ratio = 1.55, 95% CI: 1.31-1.85). ART adherence was similarly good in both groups. Adjusting for gender and baseline CD4 cell count, TB patients experienced virtually identical rise in CD4 counts after ART initiation as those without. However, the overall CD4 count at one year was lower among patients with TB (251 versus 269 cells/µl). Conclusions: Clinically detected TB disease is associated with greater mortality and morbidity despite salutary response to ART. Data suggest that identifying HIV patients co-infected with TB earlier in the HIV-disease trajectory may not fully address TB-related morbidity and mortality.Item ADHD-related sex differences in emotional symptoms across development(Springer, 2024) De Ronda, Alyssa C.; Rice, Laura; Zhao, Yi; Rosch, Keri S.; Mostofsky, Stewart H.; Seymour, Karen E.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthTo investigate developmental changes in emotion dysregulation (ED) and associated symptoms of emotional lability, irritability, anxiety, and depression, among girls and boys with and without ADHD from childhood through adolescence. Data were collected from a sample of 8-18-year-old children with (n = 264; 76 girls) and without (n = 153; 56 girls) ADHD, with multiple time-points from a subsample of participants (n = 121). Parents and youth completed rating scales assessing child ED, emotional lability, irritability, anxiety, and depression. Mixed effects models were employed to examine effects and interactions of diagnosis, sex [biological sex assigned at birth], age among boys and girls with and without ADHD. Mixed effects analyses showed sexually dimorphic developmental patterns between boys and girls, such that boys with ADHD showed a greater reduction in ED, irritability, and anxiety with age compared to girls with ADHD, whose symptom levels remained elevated relative to TD girls. Depressive symptoms were persistently elevated among girls with ADHD compared to boys with ADHD, whose symptoms decreased with age, relative to same-sex TD peers. While both boys and girls with ADHD showed higher levels of ED during childhood (compared to their sex-matched TD peers), mixed effects analyses revealed substantial sexually dimorphic patterns of emotional symptom change during adolescence: Boys with ADHD showed robust improvements in emotional symptoms from childhood to adolescence while girls with ADHD continued to show high and/or increased levels of ED, emotional lability, irritability, anxiety and depression.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 Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research(Springer Nature, 2025) Cai, Na; Verhulst, Brad; Andreassen, Ole A.; Buitelaar, Jan; Edenberg, Howard J.; Hettema, John M.; Gandal, Michael; Grotzinger, Andrew; Jonas, Katherine; Lee, Phil; Mallard, Travis T.; Mattheisen, Manuel; Neale, Michael C.; Nurnberger, John I., Jr.; Peyrot, Wouter J.; Tucker-Drob, Elliot M.; Smoller, Jordan W.; Kendler, Kenneth S.; Biochemistry and Molecular Biology, School of MedicinePsychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions. In this review we discuss how estimates of comorbidity and identification of shared genetic loci between disorders can be influenced by how disorders are measured (phenotypic assessment) and the inclusion or exclusion criteria in individual genetic studies (sample ascertainment). Specifically, the depth of measurement, source of diagnosis, and time frame of disease trajectory have major implications for the clinical validity of the assessed phenotypes. Further, biases introduced in the ascertainment of both cases and controls can inflate or reduce estimates of genetic correlations. The impact of these design choices may have important implications for large meta-analyses of cohorts from diverse populations that use different forms of assessment and inclusion criteria, and subsequent cross-disorder analyses thereof. We review how assessment and ascertainment affect genetic findings in both univariate and multivariate analyses and conclude with recommendations for addressing them in future research.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 Clinical Diversity in a Randomized Trial that Explicitly Sought Racial/Ethnic Diversity in its Sample: Baseline Comparisons in a Treatment of Youth Substance Use and Posttraumatic Stress(American Psychological Association, 2023) Andrews, Arthur R., III; Walker, Jesse; Bernard, Donte L.; Adams, Zachary; de Arellano, Michael; Kmett Danielson, Carla; Psychiatry, School of MedicineObjective: For more than two decades, federal agencies have sought to address a persistent lack of inclusion of Black, Latinx, Asian, and indigenous peoples in randomized controlled trials (RCTs), often with an underlying hypothesis that such efforts will increase diversity across clinically-relevant dimensions. We examined racial/ethnic and clinical diversity, including racial/ethnic differences in prior service access and symptom dimensions, in an RCT focusing on trauma-related mental health and substance use among adolescents. Method: Participants were 140 adolescents in an RCT of Reducing Risk through Family Therapy. Recruitment followed several recommendations for enhancing diversity. Structured interviews examined trauma exposure, posttraumatic stress disorder (PTSD) and depression symptoms, substance use, service utilization, and demographics. Results: Non-Latinx (NL) Black youth were more likely to receive mental health services for the first time and have greater trauma exposure, but less likely to report symptoms of depression (ps < .05) relative to NL White youth. Relevant caregiver differences included that NL Black caregivers were more likely to be unemployed and looking for work (p < .05) despite having similar levels of education relative to NL White caregivers (p > .05). Conclusion: Results suggest that efforts to expand racial/ethnic diversity in an RCT of combined substance use and trauma-focused mental health may also expand other clinical dimensions. Many of these differences reflect multiple dimensions of racism experienced by NL Black families that clinicians must attend to.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 burden may be associated with increased mortality in patients with severe acute liver injury referred for liver transplantation(International Scientific Information, Inc., 2020-11-03) Steiner-Temnykh, Lindsey; Dakhoul, Lara; Slaven, James; Nephew, Lauren; Patidar, Kavish R.; Orman, Eric; Desai, Archita P.; Vilar-Gomez, Eduardo; Kubal, Chandrashekhar; Ekser, Burcin; Chalasani, Naga; Chabril, MarwanSevere acute liver injury (S-ALI) can lead to acute liver and multisystem failure, with high mortality and need for liver transplantation (LT); however, the burden and impact of liver disease and comorbid conditions are unknown.Item Comorbidity of PTSD, Major Depression, and Substance Use Disorder among Adolescent Victims of the Spring 2011 Tornadoes in Alabama and Joplin, Missouri(Taylor & Francis, 2015) Adams, Zachary W.; Danielson, Carla Kmett; Sumner, Jennifer A.; McCauley, Jenna L.; Cohen, Joseph R.; Ruggiero, Kenneth J.; Psychiatry, School of MedicineObjective: The purpose of this study was twofold: (1) to estimate the prevalence of comorbid posttraumatic stress disorder (PTSD), major depressive episode (MDE), and substance use disorder (SUD); and (2) to identify risk factors for patterns of comorbidity among adolescents affected by disasters. Method: A population-based sample of 2,000 adolescents (51% female; 71% Caucasian, 26% African American) aged 12 to 17 years (M = 14.5, SD = 1.7) and their parents was recruited from communities affected by the spring 2011 tornadoes in Alabama and Joplin, Missouri. Participants completed structured telephone interviews assessing demographic characteristics, impact of disaster, prior trauma history, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), symptoms of posttraumatic stress disorder (PTSD) and major depressive episode (MDE), and substance use disorder (SUD) symptoms. Prevalence estimates were calculated for PTSD + MDE, PTSD + SUD, MDE + SUD, and PTSD + MDE + SUD. Hierarchical logistic regression was used to identify risk factors for each comorbidity profile. Results: Overall prevalence since the tornado was 3.7% for PTSD + MDE, 1.1% for PTSD + SUD, 1.0% for MDE + SUD, and 0.7% for PTSD + MDE + SUD. Girls were significantly more likely than boys to meet criteria for PTSD + MDE and MDE + SUD (ps < .05). Female gender, exposure to prior traumatic events, and persistent loss of services were significant risk factors for patterns of comorbidity. Parental injury was associated with elevated risk for PTSD + MDE. Adolescents should be evaluated for comorbid problems, including SUD, following disasters so that appropriate referrals to evidence-based treatments can be made. Conclusions: Results suggest that screening procedures to identify adolescents at risk for comorbid disorders should assess demographic characteristics (gender), impact of the disaster on the family, and adolescents' prior history of stressful events.