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Item Ambulatory BP Phenotypes and Their Association with Target Organ Damage and Clinical Outcomes in CKD(American Society of Nephrology, 2020-04-07) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of MedicineItem Assessment and Management of Hypertension among Patients on Peritoneal Dialysis(American Society of Nephrology., 2019-02-07) Vaios, Vasilios; Georgianos, Panagiotis I.; Liakopoulos, Vassilios; Agarwal, Rajiv; Medicine, School of MedicineApproximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.Item Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL(Wolters Kluwer, 2021-11-30) Majithia, Arjun; Bhatt, Deepak L.; Friedman, Allon N.; Miller, Michael; Steg, Ph. Gabriel; Brinton, Eliot A.; Jacobson, Terry A.; Ketchum, Steven B.; Juliano, Rebecca A.; Jiao, Lixia; Doyle, Ralph T., Jr.; Granowitz, Craig; Budoff, Matthew; Mason, R. Preston; Tardif, Jean-Claude; Boden, William E.; Ballantyne, Christie M.; Medicine, School of MedicineBackground: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. Methods: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). Results: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76). Conclusions: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories.Item The Case for a Bariatric-Centered Approach to CKD Care(American Society of Nephrology, 2019-02-07) Friedman, Allon N.; Medicine, School of MedicineItem Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKD(American Society of Nephrology, 2019-05-07) Sinha, Arjun D.; Agarwal, Rajiv; Medicine, School of MedicineCKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting α-agonists. Recent evidence suggests that β-adrenergic blocking agents may have a greater role in patients on dialysis and that thiazide diuretics may have a greater role in patients with advanced CKD. We conclude with sharing our general prescribing algorithm for both patients with predialysis CKD and patients with ESKD on dialysis.Item Depression, Anxiety, and Suicidality in Individuals With Chronic Traumatic Brain Injury Before and During the COVID-19 Pandemic: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study(Elsevier, 2023) Katta-Charles, Sheryl; Adams, Leah M.; Chiaravalloti, Nancy D.; Hammond, Flora M.; Perrin, Paul B.; Rabinowitz, Amanda R.; Venkatesan, Umesh M.; Weintraub, Alan H.; Bombardier, Charles H.; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the prevalence, severity, and correlates of depression, anxiety, and suicidal ideation in people with traumatic brain injury (TBI) assessed before and during the COVID-19 pandemic. Design: Retrospective cohort study using data collected through the Traumatic Brain Injury Model Systems (TBIMS) network at 1, 2, 5, 10, 15, 20, 25, or 30 years post TBI. Setting: United States-based TBIMS rehabilitation centers with telephone assessment of community residing participants. Participants: Adults (72.4% male; mean age, 47.2 years) who enrolled in the TBIMS National Database and completed mental health questionnaires prepandemic (January 1, 2017 to February 29, 2020; n=5000) or during pandemic (April 1, 2022 to June 30, 2021; n=2009) (N=7009). Interventions: Not applicable. Main outcome measures: Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 questionnaire. Results: Separate linear and logistic regressions were constructed with demographic, psychosocial, injury-related, and functional characteristics, along with a binary indicator of COVID-19 pandemic period (prepandemic vs during pandemic), as predictors of mental health outcomes. No meaningful differences in depression, anxiety, or suicidal ideation were observed before vs during the COVID-19 pandemic. Correlations between predictors and mental health outcomes were similar before and during the pandemic. Conclusions: Contrary to our predictions, the prevalence, severity, and correlates of mental health conditions were similar before and during the COVID-19 pandemic. Results may reflect generalized resilience and are consistent with the most recent findings from the general population that indicate only small, transient increases in psychological distress associated with the pandemic. While unworsened, depression, anxiety, and suicidal ideation remain prevalent and merit focused treatment and research efforts.Item Diagnosis and Management of Type 2 Diabetic Kidney Disease(American Society of Nephrology, 2017-08-07) Doshi, Simit M.; Friedman, Allon N.; Medicine, School of MedicineType 2 diabetic kidney disease (DKD) is the most common cause of CKD and ESRD worldwide, and carries with it enormous human and societal costs. The goal of this review is to provide an update on the diagnosis and management of DKD based on a comprehensive review of the medical literature. Topics addressed include the evolving presentation of DKD, clinical differentiation of DKD from non-DKD, a state-of-the-art evaluation of current treatment strategies, and promising emerging treatments. It is expected that the review will help clinicians to diagnose and manage patients with DKD.Item Evaluating a Prototype Clinical Decision Support Tool for Chronic Pain Treatment in Primary Care(Thieme, 2022) Allen, Katie S.; Danielson, Elizabeth C.; Downs, Sarah M.; Mazurenko, Olena; Diiulio, Julie; Salloum, Ramzi G.; Mamlin, Burke W.; Harle, Christopher A.; Health Policy and Management, School of Public HealthObjectives: The Chronic Pain Treatment Tracker (Tx Tracker) is a prototype decision support tool to aid primary care clinicians when caring for patients with chronic noncancer pain. This study evaluated clinicians' perceived utility of Tx Tracker in meeting information needs and identifying treatment options, and preferences for visual design. Methods: We conducted 12 semi-structured interviews with primary care clinicians from four health systems in Indiana. The interviews were conducted in two waves, with prototype and interview guide revisions after the first six interviews. The interviews included exploration of Tx Tracker using a think-aloud approach and a clinical scenario. Clinicians were presented with a patient scenario and asked to use Tx Tracker to make a treatment recommendation. Last, participants answered several evaluation questions. Detailed field notes were collected, coded, and thematically analyzed by four analysts. Results: We identified several themes: the need for clinicians to be presented with a comprehensive patient history, the usefulness of Tx Tracker in patient discussions about treatment planning, potential usefulness of Tx Tracker for patients with high uncertainty or risk, potential usefulness of Tx Tracker in aggregating scattered information, variability in expectations about workflows, skepticism about underlying electronic health record data quality, interest in using Tx Tracker to annotate or update information, interest in using Tx Tracker to translate information to clinical action, desire for interface with visual cues for risks, warnings, or treatment options, and desire for interactive functionality. Conclusion: Tools like Tx Tracker, by aggregating key information about past, current, and potential future treatments, may help clinicians collaborate with their patients in choosing the best pain treatments. Still, the use and usefulness of Tx Tracker likely relies on continued improvement of its functionality, accurate and complete underlying data, and tailored integration with varying workflows, care team roles, and user preferences.Item Metabolic Changes with Base-Loading in CKD(American Society of Nephrology, 2018-08-07) Scialla, Julia J.; Brown, Landon; Gurley, Susan; Corcoran, David L.; Bain, James R.; Muehlbauer, Michael J.; O’Neal, Sara K.; M. O’Connell, Thomas; Wolf, Myles; Melamed, Michal L.; Hostetter, Thomas H.; Abramowitz, Matthew K.; Otolaryngology -- Head and Neck Surgery, School of MedicineIn small, randomized studies, treatment with sodium bicarbonate slowed kidney function decline in patients with CKD, possibly by lowering urine ammonium or inhibiting the renin-angiotensin-aldosterone or endothelin-1 pathways (1). Understanding the metabolic effects of alkali supplementation may reveal new candidate mechanisms. With this goal in mind, we profiled changes in systemic metabolites after treatment with sodium bicarbonate within a previously performed crossover trial of oral sodium bicarbonate (2).Item Patterns of Functional Change Five to Ten Years after Moderate-Severe Traumatic Brain Injury(Mary Ann Liebert, Inc., 2021) Hammond, Flora M.; Malec, James F.; Corrigan, John D.; Whiteneck, Gale G.; Hart, Tessa; Dams-O’Connor, Kristen; Novack, Thomas A.; Bogner, Jennifer; Dahdah, Marie N.; Eagye, C.B.; Sevigny, Mitch; Ketchum, Jessica M.; Physical Medicine and Rehabilitation, School of MedicineThis study aims to characterize the patterns of functional change experienced between 5 and 10 years after moderate-severe traumatic brain injury (TBI). The study included TBI Model Systems national database participants (N = 372) at six sites who experienced TBI, received inpatient rehabilitation, and were followed at 5 and 10 years post-TBI. Outcome measures included self- or proxy-reported Functional Independence Measure (FIMTM) structured interview at 5 and 10 years post-TBI and domain change indices (DCIs) at 10 years to assess subjective change over the previous 5 years. When all seven FIM and subjective DCI subscales were considered together, 69% reported improvement in at least one subscale and 41% reported decline in at least one subscale; 51% reported more domains improved than declined, and 20% reported more domains declined than improved. Age at injury, post-traumatic amnesia duration, FIM, and depression and anxiety at year 5 were associated with FIM change and DCI measures. Although most persons with moderate-severe TBI do not experience widespread change from year 5 to 10 on individual FIM subscales or perceived domain-specific subscales, the vast majority do report change in one or more domains, with more improvement than decline and more change in subjective DCI than in FIM. Clinicians and researchers should be alert to the possibility of both positive and deleterious changes many years after TBI.