Research Spotlight

Raffals, L. E., Saha, S., Bewtra, M., Norris, C., Dobes, A., Heller, C., O’Charoen, S., Fehlmann, T., Sweeney, S., Weaver, A., Bishu, S., Cross, R., Dassopoulos, T., Fischer, M., Yarur, A., Hudesman, D., Parakkal, D., Duerr, R., Caldera, F., Korzenik, J., Pekow, J., Wells, K., Bohm, M., Perera, L., Kaur, M., Ciorba, M., Snapper, S., Scoville, E. A., Dalal, S., Wong, U. and Lewis, J. D. (2022). “The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).” Inflamm Bowel Dis 28(2): 192-199.

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BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

McCarthy, L., Colley, P., Nguyen, H. L. and Berhe, M. (2022). “Impact of Pharmacist Intervention in Response to Automated Molecular Diagnostic Tests of Blood Culture Results.” J Pharm Pract 35(1): 47-53.

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BACKGROUND: Rapid molecular diagnostic tests can aid in deescalating antimicrobial therapy prior to final culture and susceptibility reports. OBJECTIVE: The purpose of this study was to determine whether a new workflow that incorporated pharmacist review of these results reduced time to change in antimicrobial therapy. METHODS: This retrospective study analyzed pre- and post-implementation of pharmacist review of positive blood cultures analyzed by rapid diagnostics with clinical recommendations paged to providers. Patients 18 years of age or older initiated on empiric antibiotics were included. The primary outcome was the time to change to targeted antimicrobials. Other outcomes evaluated were rates of Clostridioides difficile (C difficile) infection, inpatient mortality, and intensive care unit and hospital lengths of stay. RESULTS: A total of 199 patients were included, with 98 and 101 patients in the pre- and post-implementation groups, respectively. The median time to change to targeted antimicrobials was significantly reduced with pharmacist intervention from 18.35 to 8.43 hours (P = 0.042). The groups had similar rates of C difficile infection (1% vs 0%, P = 0.492) and mortality (7.1% vs 5%, P = 0.564). The post-group also had significant reductions in antibiotic days of therapy (10.5 vs 9 days, P = 0.014) and intensive care unit length of stay (3.04 vs 1.44 days, P = 0.046). Median hospital length of stay was similar between the pre- and post-groups (8.5 vs 8 days, P = 0.106), respectively. CONCLUSION: Incorporating pharmacist review of rapid molecular results of blood cultures decreased time to change to targeted antimicrobials and reduced inpatient antibiotic days of therapy.

Choi, S. L., Martin, P., Cho, J., Ryou, Y. J. and Heinz, M. (2022). “Personality and compliance with COVID-19 protective measures among older Americans: Moderating effects of age, gender, and race/ethnicity.” Pers Individ Dif 189: 111499.

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Following the growing evidence that personality is related to various health behaviors, we examined whether personality traits were related to compliance with COVID-19 protective measures and evaluated the extent to which associations were moderated by age, gender, or race/ethnicity among older adults during a summer 2020 surge of COVID-19 cases in the United States. Data were from the 2020 Health and Retirement Study COVID-19 module. Multivariate ordinary least squares regression analyses were computed adjusting for health, psychosocial, and sociodemographic factors. Results indicated the significant associations between personality traits and compliance with COVID-19 measures varied by age, gender, and race/ethnicity. Specifically, the associations of agreeableness with wearing a mask and frequent handwashing were less pronounced among older compared with younger individuals. The association between extraversion and wearing masks was stronger for men than for women. The associations of agreeableness with handwashing and physical distancing were weaker for Hispanic older adults, whereas the associations of extraversion with physical distancing and using sanitizers were stronger for Hispanic older adults than for their non-Hispanic White counterparts. Implications regarding behavioral science underlying the current pandemic and future public health crises are discussed.

Chiruvolu, A., Estes, E., Stanzo, K. C., Desai, S. and Cornelius, B. C. (2022). “The effects of placental transfusion on mothers.” J Matern Fetal Neonatal Med: 1-6.

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OBJECTIVE: While there is ample evidence supporting delayed cord clamping (DCC) in neonates, the data on the maternal outcomes related to DCC are relatively sparse. Moreover, the outcomes, such as postpartum hemorrhage (PPH), were mostly reported for uncomplicated term vaginal deliveries. The objective of this study was to present the two primary maternal outcomes, incidence of PPH and change in hematocrit pre- and post-delivery in complex situations of preterm deliveries and term cesarean sections. STUDY DESIGN: Maternal data were collected prospectively since the placental transfusion process was implemented in a step-wise fashion in our delivery hospitals, starting August, 2013. These data on very preterm singleton, moderate preterm, very preterm twin gestation, late preterm deliveries and term cesarean sections with DCC or umbilical cord milking (UCM) were compared with respective retrospective cohorts of deliveries in which immediate cord clamping (ICC) was performed. RESULTS: Comparing very preterm singleton deliveries, the incidence of PPH was similar between the ICC and DCC groups (2.3% vs. 1.7%). There was no significant difference in mean hematocrit change pre- and postdelivery (3.06 ± 1.32 vs. 3.47 ± 1.52). When 45 s DCC cohort was compared with 60 s DCC cohort, there were no significant differences in the incidence of PPH (1.7% vs. 4.8%) or the hematocrit change pre- and postdelivery (3.47 ± 1.52 vs. 4.32 ± 1.88). PPH was not observed in either group when comparing retrospective ICC cohort with prospective DCC cohort with 60 s delay in very preterm twin gestation deliveries. There was no significant difference between the mean hematocrit change pre- and postdelivery (5.5 ± 3.3 vs. 5.8 ± 3.9). When moderate and early late preterm deliveries between 32° to 34(6) weeks of gestation were compared, there were no differences between the incidence of PPH (0.9% vs. 0%) or hematocrit change pre- and postdelivery (4.2 ± 2.3 vs. 4.8 ± 2.9). Comparing late preterm deliveries between 35° and 36(6) weeks of gestation, there was no significant difference in the incidence of PPH (13% vs. 11.4%) or the mean hematocrit change pre- and postdelivery (5.0 ± 3.0 vs. 5.1 ± 2.8). In term cesarean deliveries, the incidence of PPH was 2.2% in the retrospective ICC group and 1.4% in the prospective UCM group. There was no difference in mean hematocrit change pre- and postdelivery (5.9 ± 3.7 vs. 6.2 ± 2.8). CONCLUSION: DCC or UCM was not associated with the increased risk for PPH or significant change in maternal hematocrit pre- and postdelivery in very preterm singleton, moderate preterm, very preterm twin gestation, late preterm deliveries and term cesarean sections.

Seaks, C. E., Weekman, E. M., Sudduth, T. L., Xie, K., Wasek, B., Fardo, D. W., Johnson, L. A., Bottiglieri, T. and Wilcock, D. M. (2022). “Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling.” J Cereb Blood Flow Metab: 271678×211069006.

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Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind Alzheimer’s disease. Apolipoprotein E (ApoE) is a lipid transporting lipoprotein found within the brain and periphery. The APOE ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease and is a risk factor for VCID. Our lab has previously utilized a dietary model of hyperhomocysteinemia (HHcy) to induce VCID pathology and cognitive deficits in mice. This diet induces perivascular inflammation through cumulative oxidative damage leading to glial mediated inflammation and blood brain barrier breakdown. Here, we examine the impact of ApoE ε4 compared to ε3 alleles on the progression of VCID pathology and inflammation in our dietary model of HHcy. We report a significant resistance to HHcy induction in ε4 mice, accompanied by a number of related differences related to homocysteine (Hcy) metabolism and methylation cycle, or 1-C, metabolites. There were also significant differences in inflammatory profiles between ε3 and ε4 mice, as well as significant reduction in Serpina3n, a serine protease inhibitor associated with ApoE ε4, expression in ε4 HHcy mice relative to ε4 controls. Finally, we find evidence of pervasive sex differences within both genotypes in response to HHcy induction.