Research Spotlight

Akanit, U., Bozorgmehri, S., Alquadan, K., Nelson, J., Kaplan, B., Ozrazgat-Baslanti, T. and Womer, K.L. (2020). “Improved ability to achieve target trough levels with liquid versus capsule tacrolimus in kidney transplant patients with HIV on protease inhibitor- or cobicistat-based regimens.” Transpl Infect Dis Nov 20;e13517. [Epub ahead of print.].

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HIV + patients are commonly accepted for kidney transplantation. However, patients on protease inhibitor (PI)- or cobicistat (cobi)-based regimens have trouble achieving optimal tacrolimus (Tac) levels. Our study compared the ability to achieve target levels using liquid versus immediate-release capsule Tac in kidney transplant patients with HIV on PI- or cobi-based regimens. The study included four kidney transplant patients who were converted to liquid Tac due to inability to achieve acceptable drug levels on the capsule formulation. Tac trough levels were analyzed retrospectively to compare target levels before and after conversion. The individual patient time in the therapeutic range (TTR) was calculated using Rosendaal’s linear interpolation method, and the difference between before and after conversion TTR was determined. In combined data, 44.63% of all Tac trough levels were within the target range after conversion to liquid Tac compared to 22.07% prior to conversion (P < .001). Furthermore, 3.31% and 7.44% of Tac trough levels were lower than 3 ng/mL or higher than 12 ng/mL, respectively, after conversion compared to 11.72% (P = .0564) and 24.14% (P < .0001) prior to conversion. The overall mean TTR was 45.1% after conversion to liquid Tac compared to 16.2% prior to conversion (P = .097). Finally, the coefficient of variation for Tac trough levels was 42.6 after conversion compared to 56.4 prior to conversion. A significantly improved ability to achieve target trough Tac levels was achieved with liquid Tac extemporaneous versus capsule formulation in kidney transplant patients with HIV taking a PI- or cobi-based regimen.

Qi, X., Keith, K.A. and Huang, J.H. (2020). “COVID-19 and stroke: A review.” Brain Hemorrhages Nov 17. [Epub ahead of print.].

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COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Froehlich-Grobe, K., Betts, A.C., Driver, S.J., Carlton, D.N., Lopez, A.M., Lee, J. and Kramer, M.K. (2020). “Group Lifestyle Balance Adapted for Individuals With Impaired Mobility: Outcomes for 6-Month RCT and Combined Groups at 12 Months.” Am J Prev Med 59(6): 805-817.

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INTRODUCTION: This study examines the feasibility and effectiveness of an intensive lifestyle intervention adapted for people with impaired mobility. STUDY DESIGN: This was a randomized, wait-list controlled trial. The experimental group immediately received the 12-month weight loss program; the wait-list control group received it after a 6-month delay. Between-group comparisons were conducted for the 6-month RCT study design. Repeated measures were conducted for both groups combined after receiving the 12-month intervention. Data were collected August 2015-February 2017 and analyzed in 2017. SETTING/PARTICIPANTS: A community-based sample received 23, group-based sessions via a mix of telephone and in-person sessions in a hospital-based setting. Participants with impaired mobility (n=66) were middle-aged (49.80 [SD=11.37] years), mostly White (66.7%), female (66.7%), and most commonly had spinal cord injury (47.0%). INTERVENTION: The 12-month intervention delivered 23 group-based sessions that promoted weight loss through reducing caloric intake and increasing physical activity. MAIN OUTCOME MEASURES: Primary outcomes were effectiveness measured as change in weight and time spent in moderate physical activity. Feasibility was assessed in 12-month combined group analyses, measured as retention, attendance, and dietary self-monitoring. RESULTS: The 6-month RCT results showed that the immediate and delayed groups differed significantly (p<0.05) in weight (-1.66 [SD=4.42] kg loss vs 0.05 [SD=4.15] kg gain) and moderate physical activity (52.93 [SD=90.74] minutes/week increase vs -14.22 [SD=96.02] minutes/week decrease), accounting for baseline weight, time with disability, and age of onset. The 12-month results with groups combined demonstrated 74.2% retention and 77.7% core session attendance. Self-monitoring was higher in the delayed group (77.3%), who used a smartphone app, than the immediate group (47.3%), who mostly used paper trackers. Participants achieved significant 12-month weight loss of 3.31 (SD=10.13) kg (d=0.33) in mixed modeling analyses with groups combined yet did not significantly increase moderate physical activity. CONCLUSIONS: Group Lifestyle Balance Adapted for Individuals with Impaired Mobility is a feasible, effective approach to teach healthy lifestyle skills to individuals with mobility impairment, yielding modest weight loss and enhanced self-efficacy. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT03307187.

Grayburn, P.A., Packer, M., Sannino, A. and Stone, G.W. (2020). “Disproportionate secondary mitral regurgitation: myths, misconceptions and clinical implications.” Heart Nov 24;heartjnl-2020-316992. [Epub ahead of print.].

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Secondary (functional) mitral regurgitation (SMR) most commonly arises secondary to left ventricular (LV) dilation/dysfunction. The concept of disproportionately severe SMR was proposed to help explain the different results of two randomised trials of transcatheter edge-to-edge mitral valve repair (TEER) versus medical therapy. This concept is based on the fact that effective regurgitant orifice area (EROA) depends on LV end-diastolic volume (LVEDV), ejection fraction, regurgitant fraction and the velocity-time integral of SMR. This review focuses on the haemodynamic framework underlying the concept and the myths and misconceptions arising from it. Each component of EROA/LVEDV is prone to measurement error which can result in misclassification of individual patients. Moreover, EROA is typically measured at peak systole rather than its mean value over the duration of MR. This can result in physiologically impossible values of EROA or regurgitant volume. Although the EROA/LVEDV ratio (1) emphasises that grading MR severity needs to consider LV size and function and (2) helps explain the different outcomes between COAPT and MITRAFR, there are important factors that are not included. Among these are left atrial compliance, LV pressure and ejection fraction, pulmonary hypertension, right ventricular function and tricuspid regurgitation. Because medical therapy can reduce LV volumes and improve both LV function and SMR severity, the key to patient selection is forced titration of neurohormonal antagonists to the target doses that have been proven in clinical trials (along with cardiac resynchronisation when appropriate). Patients who continue to have symptomatic severe SMR after doing so should be considered for TEER.

Pollifrone, M., Callender, L., Bennett, M., Driver, S., Petrey, L., Hamilton, R. and Dubiel, R. (2020). “Predictors for 30-Day Readmissions After Traumatic Brain Injury.” J Head Trauma Rehabil Nov 13. [Epub ahead of print.].

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OBJECTIVE: To examine predictors for 30-day readmission post-onset of traumatic brain injury (TBI) after initial trauma hospitalization. DESIGN: Retrospective cohort. PARTICIPANTS: In total, 5284 patients with an acute TBI admitted from January 1, 2006, through December 31, 2015. METHODS: Demographic and clinical data after initial TBI onset were extracted from the local trauma registry and matched with the Dallas-Fort Worth Hospital Council registry. Multiple logistic regression analysis was used to determine factors significantly associated with 30-day readmission. Top diagnosis codes for 30-day readmission were also described. RESULTS: Patients were primarily male (64.6%), non-Hispanic White (47.6%), uninsured (35.4%), and aged 46.1 ± 23.3 years. In total, 448 patients (8.5%) had a 30-day readmission. Median cumulative charges for each readmitted subject was $34 313. Factors significantly associated with 30-day readmission were falling as the cause of injury, having increased Charlson Comorbidity Index and Injury Severity Score, and discharging to a skilled nursing facility or long-term acute care. Being uninsured was associated with decreased odds of a 30-day readmission. Top diagnosis codes among the readmission visits included cardiac codes (57.7%), fluid and acid-base disorders (54.8%), and hypertension (50.1%). CONCLUSION: These data highlight those at risk for 30-day readmission across a diverse population of TBI at a large medical center. Interventions such as health literacy education or patient navigation may help mitigate 30-day readmission for at-risk patients.