Research Spotlight

Warren, A. M., K. McMinn, G. Testa, A. Wall, G. Saracino and L. Johannesson (2021). “Motivations and Psychological Characteristics of Nondirected Uterus Donors From The Dallas UtErus Transplant Study.” Prog Transplant Oct 29;15269248211046027. [Epub ahead of print]. 15269248211046027.

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INTRODUCTION: Uterus transplantation has demonstrated success in clinical trials. Questions regarding how it should transition to a clinical procedure must be addressed. A critical element is an evidence regarding the psychological experiences of living uterus donors, especially donors who are nondirected (altruistic). PROJECT AIMS: To describe the motivations for donation, psychological characteristics, and mental health history of nondirected living uterus donors in the Dallas UtErus Transplant Study (NCT02656550). DESIGN: An observational design was used to evaluate 44 self-referred nondirected uterus donors for the uterus transplant program. The donors participated in a clinical interview with a licensed psychologist and completed assessment instruments for depression, anxiety, posttraumatic stress, health-related quality of life, and resilience at the time of evaluation. RESULTS: Among the 11 donors, the median age was 36 years, 10 were married, 10 were of non-Hispanic/Latino ethnicity, and all had given birth (median of 2 children). The most frequent motivations for the donation were to provide another woman with the opportunity to carry her own child and to contribute to science. No participants met clinical criteria for depression, anxiety or posttraumatic stress but 4 reported current mental health conditions and 7 reported past or present treatment. Quality of life and resilience scores were above population norms. CONCLUSION: Women selected as nondirected uterus donors were motivated to help other women experience carrying their own child and to contribute to science. A minority of women reported mental health conditions and/or treatment, and this was determined not to exclude participation with uterus donation.

Hall, L. R., K. Sanchez, B. da Graca, M. M. Bennett, M. Powers and A. M. Warren (2021). “Income Differences and COVID-19: Impact on Daily Life and Mental Health.” Popul Health Manag Oct 14. [Epub ahead of print].

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The COVID-19 pandemic has caused disproportionate suffering among vulnerable and socioeconomically disadvantaged portions of the population. Low-income and minority populations are likely to experience disparate disease and mental health burdens. Currently, there is little evidence regarding how the experience of the early months of the US COVID-19 outbreak differed by income level, and how that related to mental health symptoms. The present study used data from a national sample of US adults (n = 5023) who completed measures related to the COVID experience, the COVID-19 Fear Scale, the Generalized Anxiety Disorder-7 (GAD-7), and the Patient Health Questionnaire-8 (PHQ-8). Multivariable regression was performed to determine whether income level (low: <$45,000 vs high: ≥$75,000) was significantly associated with COVID experience measures, PHQ-8, GAD-7, and COVID fear scores. Among the low-income group, COVID-19 had a significantly greater negative impact on: family income/employment, access to food, access to mental health treatment, and stress and discord in the family. Participants in the low-income group also had greater odds of a PHQ-8 score ≥10 (odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.08, 1.77) and a GAD-7 score ≥10 (OR = 1.65, 95% CI 1.27, 2.14) compared to those in the high-income group. Study findings suggest substantial differences in how COVID-19 impacted daily life and mental health between adults living in low-income households compared to high-earning households during the early months of the pandemic.

Kates, O. S., P. G. Stock, M. G. Ison, R. D. M. Allen, P. Burra, J. C. Jeong, V. Kute, E. Muller, A. Nino-Murcia, H. Wang and A. Wall (2021). “Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.” Am J Transplant Oct 27. [Epub ahead of print].

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Transplant centers seeking to increase COVID-19 vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.

Loomba, R., R. Mohseni, K. J. Lucas, J. A. Gutierrez, R. G. Perry, J. F. Trotter, R. S. Rahimi, S. A. Harrison, V. Ajmera, J. D. Wayne, M. O’Farrell, W. McCulloch, K. Grimmer, M. Rinella, V. Wai-Sun Wong, V. Ratziu, G. J. Gores, B. A. Neuschwander-Tetri and G. Kemble (2021). “TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial.” Gastroenterology 161(5): 1475-1486.

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BACKGROUND & AIMS: Increased de novo lipogenesis creates excess intrahepatic fat and lipotoxins, propagating liver damage in nonalcoholic steatohepatitis. TVB-2640, a fatty acid synthase inhibitor, was designed to reduce excess liver fat and directly inhibit inflammatory and fibrogenic pathways. We assessed the safety and efficacy of TVB-2640 in patients with nonalcoholic steatohepatitis in the United States. METHODS: 3V2640-CLIN-005 (FASCINATE-1) was a randomized, placebo-controlled, single-blind study at 10 US sites. Adults with ≥8% liver fat, assessed by magnetic resonance imaging proton density fat fraction, and evidence of liver fibrosis by magnetic resonance elastography ≥2.5 kPa or liver biopsy were eligible. Ninety-nine patients were randomized to receive placebo or 25 mg or 50 mg of TVB-2640 (orally, once-daily for 12 weeks). The primary end points of this study were safety and relative change in liver fat after treatment. RESULTS: Liver fat increased in the placebo cohort by 4.5% relative to baseline; in contrast TVB-2640 reduced liver fat by 9.6% in the 25-mg cohort (n = 30; least squares mean: -15.5%; 95% confidence interval, -31.3 to -0.23; P = .053), and 28.1% in the 50-mg cohort (n = 28; least squares mean: -28.0%; 95% confidence interval, -44.5 to -11.6; P = .001). Eleven percent of patients in the placebo group achieved a ≥30% relative reduction of liver fat compared to 23% in the 25-mg group, and 61% in the 50-mg group (P < .001). Secondary analyses showed improvements of metabolic, pro-inflammatory and fibrotic markers. TVB-2640 was well tolerated; adverse events were mostly mild and balanced among the groups. CONCLUSIONS: TVB-2640 significantly reduced liver fat and improved biochemical, inflammatory, and fibrotic biomarkers after 12 weeks, in a dose-dependent manner in patients with nonalcoholic steatohepatitis. ClinicalTrials.gov, Number NCT03938246.

Cooper-DeHoff, R. M., V. Fontil, T. Carton, A. M. Chamberlain, J. Todd, E. C. O’Brien, K. M. Shaw, M. Smith, S. Choi, E. K. Nilles, D. Ford, K. M. Tecson, P. E. Dennar, F. Ahmad, S. Wu, J. C. McClay, K. Azar, R. Singh, M. Faulkner Modrow, C. M. Shay, M. Rakotz, G. Wozniak and M. J. Pletcher (2021). “Tracking Blood Pressure Control Performance and Process Metrics in 25 US Health Systems: The PCORnet Blood Pressure Control Laboratory.” J Am Heart Assoc 10(21): e022224.

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Background The National Patient-Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross-sectional study with queries against standardized electronic health record data in the National Patient-Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well-documented hypertension and a recent encounter at the health system for a series of 1-year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient-years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%-74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66-0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%-25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5-18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.