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Item 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 Change in Platelet Count after Transjugular Intrahepatic Portosystemic Shunt Creation: An Advancing Liver Therapeutic Approaches (ALTA) Group Study(Elsevier, 2023) Wong, Randi J.; Ge, Jin; Boike, Justin; German, Margarita; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Desai, Archita; Couri, Thomas; Paul, Sonali; Frenette, Catherine; Verna, Elizabeth C.; Goel, Aparna; Fallon, Michael; Thornburg, Bartley; VanWagner, Lisa; Lai, Jennifer C.; Kolli, K. Pallav; Medicine, School of MedicinePurpose To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation. Materials and Methods Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×109/L. Results A total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (−26 × 109/L to 25 × 109/L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 109/L; 95% CI, 0.97–0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10–1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02–1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11–2.02) was the only factor associated with top quartile platelet increase in this subgroup. Conclusions TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 109/L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 109/L.Item Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study(Wolters Kluwer, 2021) Ge, Jin; Lai, Jennifer C.; Boike, Justin Richard; German, Margarita; Jest, Nathaniel; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Lee, Alexander; Hristov, Alexander; Desai, Archita P.; Junna, Shilpa; Pokhrel, Bhupesh; Couri, Thomas; Paul, Sonali; Frenette, Catherine; Christian-Miller, Nathaniel; Laurito, Marcela; Verna, Elizabeth C.; Rahim, Usman; Goel, Aparna; Das, Arighno; Pine, Stewart; Gregory, Dyanna; VanWagner, Lisa B.; Kolli, Kanti Pallav; Advancing Liver Therapeutic Approaches (ALTA) Study Group; Medicine, School of MedicineTransjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.Item Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study(Wolters Kluwer, 2021) Boike, Justin Richard; Mazumder, Nikhilesh Ray; Kolli, Kanti Pallav; Ge, Jin; German, Margarita; Jest, Nathaniel; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Lai, Jennifer C.; Desai, Archita P.; Couri, Thomas; Paul, Sonali; Frenette, Catherine; Verna, Elizabeth C.; Rahim, Usman; Goel, Aparna; Gregory, Dyanna; Thornburg, Bartley; VanWagner, Lisa B.; Advancing Liver Therapeutic Approaches (ALTA) Study Group; Medicine, School of MedicineIntroduction: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. Methods: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). Results: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). Discussion: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.Item The impact of right atrial pressure on outcomes in patients undergoing TIPS, an ALTA group study(Wolters Kluwer, 2023) Bommena, Shoma; Mahmud, Nadim; Boike, Justin R.; Thornburg, Bartley G.; Kolli, Kanti P.; Lai, Jennifer C.; German, Margarita; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Desai, Archita P.; Junna, Shilpa; Paul, Sonali; Frenette, Catherine; Verna, Elizabeth C.; Goel, Aparna; Gregory, Dyanna; Padilla, Cynthia; VanWagner, Lisa B.; Fallon, Michael B.; Advancing Liver Therapeutic Approaches (ALTA) Study Group; Medicine, School of MedicineBackground and aims: Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database. Approach and results: Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes.Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p =0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets. Conclusions: Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.