Browsing by Author "Gupta, Samir"
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Item 547. A Retrospective Cohort Study of Treatment Patterns and Clinical Outcomes in Patients with COVID-19(Oxford, 2020-10) Pritchard, Haley; Hiles, Jon; Teresa, Batteiger; Desai, Armisha; Wrin, Justin E; Hlavaty, Ariel; Agard, Amanda; Hinton, Bradley; Lucky, Christine W; Fleming, Elizabeth; Khan, Humaira; Bomkamp, John P; Derringer, Jon; Schneider, Jack; Ryder, Jonathan; Russ, Jason D; Khan, Haseeba; Kleyman, Svetlana; Enane, Leslie A; Stack, Matthew; Kussin, Michelle L; Myers, Courtney; Nagy, Allysa; Richardson, Noah; Elsheikh, Omar; Rahman, Omar; Kruer, Rachel; Trigonis, Russell; Butt, Saira; Bhumbra, Samina; Kapil, Sasha; Abi-Mansour, Tanya; Howe, Zachary; Abdallah, Wassim; Gupta, Samir; Wools-Kaloustian, Kara; Medicine, School of MedicineItem Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial(American Medical Association, 2023-07-03) Robertson, Douglas J.; Dominitz, Jason A.; Beed, Alexander; Boardman, Kathy D.; Del Curto, Barbara J.; Guarino, Peter D.; Imperiale, Thomas F.; LaCasse, Andrew; Larson, Meaghan F.; Gupta, Samir; Lieberman, David; Planeta, Beata; Shaukat, Aasma; Sultan, Shanaz; Menees, Stacy B.; Saini, Sameer D.; Schoenfeld, Philip; Goebel, Stephan; von Rosenvinge, Erik C.; Baffy, Gyorgy; Halasz, Ildiko; Pedrosa, Marcos C.; Kahng, Lyn Sue; Cassim, Riaz; Greer, Katarina B.; Kinnard, Margaret F.; Bhatt, Divya B.; Dunbar, Kerry B.; Harford, William V.; Mengshol, John A.; Olson, Jed E.; Patel, Swati G.; Antaki, Fadi; Fisher, Deborah A.; Sullivan, Brian A.; Lenza, Christopher; Prajapati, Devang N.; Wong, Helen; Beyth, Rebecca; Lieb, John G.; Manlolo, Joseph; Ona, Fernando V.; Cole, Rhonda A.; Khalaf, Natalia; Kahi, Charles J.; Kohli, Divyanshoo Rai; Rai, Tarun; Sharma, Prateek; Anastasiou, Jiannis; Hagedorn, Curt; Fernando, Ronald S.; Jackson, Christian S.; Jamal, M. Mazen; Lee, Robert H.; Merchant, Farrukh; May, Folasade P.; Pisegna, Joseph R.; Omer, Endashaw; Parajuli, Dipendra; Said, Adnan; Nguyen, Toan D.; Tombazzi, Claudio Ruben; Feldman, Paul A.; Jacob, Leslie; Koppelman, Rachel N.; Lehenbauer, Kyle P.; Desai, Deepak S.; Madhoun, Mohammad F.; Tierney, William M.; Ho, Minh Q.; Hockman, Heather J.; Lopez, Christopher; Carter Paulson, Emily; Tobi, Martin; Pinillos, Hugo L.; Young, Michele; Ho, Nancy C.; Mascarenhas, Ranjan; Promrat, Kirrichai; Mutha, Pritesh R.; Pandak, William M.; Shah, Tilak; Schubert, Mitchell; Pancotto, Frank S.; Gawron, Andrew J.; Underwood, Amelia E.; Ho, Samuel B.; Magno-Pagatzaurtundua, Priscilla; Toro, Doris H.; Beymer, Charles H.; Kaz, Andrew M.; Elwing, Jill; Gill, Jeffrey A.; Goldsmith, Susan F.; Yao, Michael D.; Protiva, Petr; Pohl, Heiko; Kyriakides, Tassos; CONFIRM Study Group; Medicine, School of MedicineImportance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, setting, and participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main outcomes and measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.Item Cystatin C based estimation of glomerular filtration rate and association with atherosclerosis imaging markers in people living with HIV(Wolters Kluwer, 2020-07) Mcclean, Mitchell; Buzkova, Petra; Budoff, Matthew; Estrella, Michelle; Freiberg, Matthew; Hodis, Howard N.; Palella, Frank; Shikuma, Cecilia; Post, Wendy S.; Gupta, Samir; Medicine, School of MedicineIntroduction: Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating Cystatin C (CysC) measurements are more predictive of preclinical CVD than those using only creatinine (Cr). Objectives: The study aimed to determine which of the three Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score. Methods: This cross-sectional analysis of pooled data from three large cohorts compared the associations between the three CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC. Results: 1487 participants were included, and of these 910 (562 HIV+, 348 HIV-) had CIMT measurements and 366 (296 HIV+, 70 HIV-) had CAC measurements available. In HIV- participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr-Cys C correlated with CIMT [β= -0.90, 95% CI (-1.67,-0.13) μm; p=0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [β= -8.63, 95% CI (-16.49,-0.77) HU; p=0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance. Conclusion: In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone.Item Insomnia and mechanistic pathways to atherosclerotic CVD in HIV(2020-08) Polanka, Brittanny M.; Stewart, Jesse; Zapolski, Tamika; Hirsh, Adam; Gupta, SamirStudy 1: Background: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. Methods: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people living with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, “Difficulty falling or staying asleep?,” with the following response options: “I do not have this symptom” or “I have this symptom and…” “it doesn’t bother me,” “it bothers me a little,” “it bothers me,” “it bothers me a lot.” Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). Results: For sCD14 and D-dimer, we observed no significant associations. For IL-6, veterans in the “bothers a lot” group had 15% higher IL-6 than veterans in the “I do not have this symptom” group in the demographic-adjusted model (exp[b]=1.15, 95%CI=1.02-1.29, p=.03). This association was nonsignificant in the fully-adjusted model (exp[b]=1.07, 95%CI=0.95-1.19, p=.25). Conclusion: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted. Study 2: Background: While insomnia has been identified as a potential risk factor for cardiovascular disease in HIV (HIV-CVD), research on the underlying pathophysiological mechanisms is scarce. Methods: We examined associations between 0-to-12-week changes in sleep disturbance and the concurrent 0-to-12-week changes and the subsequent 12-to-24-week changes in markers of systemic inflammation, coagulation, and endothelial dysfunction among people living with HIV (n = 33-38) enrolled in a depression clinical trial. Sleep disturbance was measured using the Pittsburgh Sleep Quality Index. Inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) and coagulation marker D-dimer were determined from blood specimens; endothelial dysfunction marker brachial flow-mediated dilation (FMD) was determined by ultrasound. 0-to-12-week variables were calculated as 12-week visit minus baseline, and 12-to-24-week variables were calculated as 24-week minus 12-week. We constructed multivariate linear regression models for each outcome adjusting for age, sex, race/ethnicity, Framingham risk score, and baseline depressive symptoms. Results: We did not observe statistically significant associations between 0-to-12-week changes in sleep disturbance and 0-to-12-week or 12-to-24-week changes in IL-6, CRP, D-dimer, or FMD. However, we did observe potentially meaningful associations, likely undetected due to low power. For 0-to-12-weeks, every 1-standard deviation (SD) increase, or worsening, in the sleep disturbance change score was associated with a 0.41 pg/mL and 80 ng/mL decease in IL-6 and D-dimer, respectively. For 12-to-24-weeks, every 1-SD increase in sleep disturbance change score was associated with a 0.63 mg/L, 111 ng/mL, and 0.82% increase in CRP, D-dimer, and FMD, respectively. Conclusion: We observed potentially meaningful, though not statistically significant, associations between changes in sleep disturbance and changes in biological mechanisms underlying HIV-CVD over time. Some associations were in the expected direction, but others were not. Additional studies are needed that utilize larger samples and validated, comprehensive assessments of insomnia.Item Longitudinal Relationships Between Depressive Symptom Clusters and Inflammatory Biomarkers Implicated in Cardiovascular Disease in People with Depression(2021-12) Patel, Jay Sunil; Stewart, Jesse; Cyders, Melissa; Wu, Wei; Gupta, SamirSystemic inflammation is one potential mechanism underlying the depression to cardiovascular disease (CVD) relationship. In addition, somatic rather than cognitive/affective symptoms of depression may be more predictive of poorer CVD outcomes due to systemic inflammation. However, the small existing literature in this area has yielded mixed results. Therefore, the present study aimed to examine longitudinal associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD (i.e., interleukin-6, IL-6; and C-reactive protein, CRP) using data from the eIMPACT trial. In addition, race was examined as a moderator given findings from two previous studies. The eIMPACT trial was a phase II, single-center randomized controlled trial comparing 12 months of the eIMPACT intervention to usual primary care for depression. Participants were 216 primary care patients aged ≥ 50 years with a depressive disorder and CVD risk factors but no clinical CVD from a safety net healthcare system (Mage = 58.7 years, 78% female, 50% Black, Meducation = 12.8 years). Depressive symptoms clusters (i.e., somatic and cognitive/affective clusters) were assessed using the Patient Health Questionnaire-9 (PHQ-9). IL-6 and high-sensitivity CRP were assessed by the local clinical research laboratory using R&D Systems ELISA kits. Change variables were modeled in MPlus using a latent difference score approach. The results of this study were largely null. Very few associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD were observed, and the detected relationships may be due to type I error. Similarly, only one association was observed for race as a moderator, and the detected relationship may be due to type I error. The present findings do not provide strong support for the longitudinal associations between depressive symptom clusters and inflammatory biomarkers implicated in CVD nor the moderating effects of race. However, the present findings do not rule out the possibility of these relationships given important study limitations, such as study design and power. Future prospective cohort studies with multiple waves of data collection are needed to determine the longitudinal associations between depression facets and various inflammatory biomarkers implicated in CVD. In addition, a biologically-based approach to identifying facets of depression – e.g., the endophenotype model – may provide a clearer understanding of the depression-inflammation relationship.Item Modernized Collaborative Care for Depression: Impact on Psychological Risk and Protective Factors for Diabetes and Intervention Outcomes Among Diverse Sociodemographic Groups(2024-08) Williams, Michelle; Stewart, Jesse; Hirsh, Adam; Johnson, India; Gupta, SamirObjective: We examined the effect of a modernized collaborative care intervention for depression on multiple psychological risk and protective factors for diabetes and characterized intervention process outcomes using data from the eIMPACT-DM trial. Methods: Forty-six primary care patients with depression and elevated diabetes risk from a safety net healthcare system (Mage = 50 years, 78% women, 72% Black, Meducation = 13 years, 33% with income <$10,000/year) were randomized to 6 months of the eIMPACT-DM intervention (our modernized collaborative care intervention for depression involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants; n=24) or active control (depression education, depressive symptom monitoring, and usual primary care for depression; n=22). Depressive symptoms (Patient Health Questionnaire-9 [PHQ-9], anxiety symptoms (Generalized Anxiety Disorder-7 [GAD-7]), trait positive affect (Positive and Negative Affect Schedule- Positive Affect Subscale [PANAS-PA]), life satisfaction (Satisfaction With Life Scale [SWLS]), and intervention process outcomes were measured across the treatment period. Results: Effect size metrics (standardized regression coefficients; bY) indicated that, compared to active control, the intervention group demonstrated clinically meaningful medium-to-large improvements in depressive symptoms (PHQ-9 bY = -0.69), anxiety symptoms (GAD-7 bY = - 0.76), and trait positive affect (PANAS-PA bY = 0.61) as well as small-to-medium improvements in life satisfaction (bY = 0.43). Although only 27% of participants assigned to iCBT had good engagement and 60% had good iCBT comprehension, the intervention group reported high skills implementation and treatment satisfaction. Conclusion: These findings demonstrate the potential of a modernized collaborative care intervention to improve multiple psychological risk and protective factors for diabetes in a diverse primary care population. Such an intervention could ultimately serve to bolster future diabetes prevention in diverse groups, helping to reduce diabetes-related health disparities.Item Plasma apolipoprotein L1 levels do not correlate with CKD(American Society of Nephrology, 2014-03) Bruggeman, Leslie A.; O'Toole, John F.; Ross, Michael D.; Madhavan, Sethu M.; Smurzynski, Marlene; Wu, Kunling; Bosch, Ronald J.; Gupta, Samir; Pollak, Martin R.; Sedor, John R.; Kalayjian, Robert C.; Department of Medicine, IU School of MedicinePolymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.Item Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells(The American Association of Immunologists, 2014-10-01) Lan, Jie; Yang, Kai; Byrd, Daniel; Hu, Ningjie; Amet, Tohti; Shepherd, Nicole; Desai, Mona; Gao, Jimin; Gupta, Samir; Sun, Yongtao; Yu, Qigui; Department of Microbiology & Immunology, IU School of MedicineLatently HIV-1-infected cells are recognized as the last barrier toward viral eradication and cure. To purge these cells, we combined a provirus stimulant with a blocker of human CD59, a key member of the regulators of complement activation, to trigger Ab-dependent complement-mediated lysis. Provirus stimulants including prostratin and histone deacetylase inhibitors such as romidepsin and suberoylanilide hydroxamic acid activated proviruses in the latently HIV-1-infected T cell line ACH-2 as virion production and viral protein expression on the cell surface were induced. Romidepsin was the most attractive provirus stimulant as it effectively activated proviruses at nanomolar concentrations that can be achieved clinically. Antiretroviral drugs including two protease inhibitors (atazanavir and darunavir) and an RT inhibitor (emtricitabine) did not affect the activity of provirus stimulants in the activation of proviruses. However, saquinavir (a protease inhibitor) markedly suppressed virus production, although it did not affect the percentage of cells expressing viral Env on the cell surface. Provirus-activated ACH-2 cells expressed HIV-1 Env that colocalized with CD59 in lipid rafts on the cell surface, facilitating direct interaction between them. Blockage of CD59 rendered provirus-activated ACH-2 cells and primary human CD4(+) T cells that were latently infected with HIV-1 sensitive to Ab-dependent complement-mediated lysis by anti-HIV-1 polyclonal Abs or plasma from HIV-1-infected patients. Therefore, a combination of provirus stimulants with regulators of complement activation blockers represents a novel approach to eliminate HIV-1.Item Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer(Elsevier, 2020-03) Gupta, Samir; Lieberman, David; Anderson, Joseph C.; Burke, Carol A.; Dominitz, Jason A.; Kaltenbach, Tonya; Robertson, Douglas J.; Shaukat, Aasma; Syngal, Sapna; Rex, Douglas K.; Medicine, School of MedicineItem Spotlight: US Multi-Society Task Force on Colorectal Cancer Recommendations for Follow-up After Colonoscopy and Polypectomy(Elsevier, 2020-03) Gupta, Samir; Lieberman, David; Anderson, Joseph C.; Burke, Carol A.; Dominitz, Jason A.; Kaltenbach, Tonya; Robertson, Douglas J.; Shaukat, Aasma; Syngal, Sapna; Rex, Douglas K.; Medicine, School of Medicine