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Item Active and receptive arts participation and their association with mortality among adults in the United States: a longitudinal cohort study(Elsevier, 2021) Story, Kristin M.; Yang, Ziyi; Bravata, Dawn M.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthObjectives: The aim of the study was to explore associations between active and receptive arts participation and all-cause mortality among adults in the United States population. Study design: This was a prospective cohort study. Methods: Data were derived from the Health and Retirement Study. Separate Cox proportional hazards models were constructed for two cohorts (2012 and 2014) to examine associations between arts participation and mortality. Results: Independent of sociodemographic and health factors, participants aged ≥65 years had a higher mortality risk if they did not engage in music listening, hazard ratio (HR) 1.39 (95% confidence interval [CI]: 1.12-1.71); singing/playing an instrument, HR 1.49 (95% CI: 1.07-2.0); or doing arts and crafts, HR 1.39 (95% CI: 1.00-1.92). For participants aged <65 years, there was a higher mortality risk if they did not listen to music, HR 1.79 (95% CI: 1.07-3.01). Older participants from the 2014 cohort had a higher mortality risk if they did not engage in active arts, HR 1.73 (95% CI: 1.08-2.77). Conclusions: Engagement in the arts was associated with lower risk of mortality even after risk adjustment, especially for adults aged ≥65 years. Greater access and integration of arts in everyday life is recommended.Item Anemia and Iron-Deficiency Anemia in Children Born to Mothers with HIV in Western Kenya(Sage, 2021-02-22) Oyungu, Eren; Roose, Anna W.; Ombitsa, Ananda R.; Yang, Ziyi; Vreeman, Rachel C.; McHenry, Megan S.; Pediatrics, School of MedicineThe objective of this study was to determine and compare anemia and iron-deficiency anemia (IDA) rates in young Kenyan children who are HIV infected (HI), HIV exposed, uninfected (HEU), and HIV unexposed (HU). Questionnaires, anthropometrics, and blood samples were collected from HI, HEU, and HU aged 18 to 36 months. Descriptive statistics, Fisher’s exact tests, and linear regression were used for analysis. Of 137 total participants, HI (n = 18), HEU (n = 70), and HU (n = 49), 61.1%, 53.6%, and 36.7%, respectively, were anemic, with mean hemoglobin levels highest in HU (P = .006). After adjusting for covariates, HI (β = −9.6, 95% CI:−17.3 to −2.0) and HEU (β = −7.4, 95% CI: −12.9 to −1.9) had lower hemoglobin levels compared with HU. The proportion of children with IDA did not differ significantly across groups (P = .08). HEU have rates of anemia and IDA similar to HI. Anemia risk is generally higher in HEU than HU, even after adjusting for covariates.Item Are Newborn Outcomes Different for Term Babies Who Were Exposed to Antenatal Corticosteroids?(Elsevier, 2021) McKinzie, Alexandra H.; Yang, Ziyi; Teal, Evgenia; Daggy, Joanne K.; Tepper, Robert S.; Quinney, Sarah K.; Rhoads, Eli; Haneline, Laura S.; Haas, David M.; Obstetrics and Gynecology, School of MedicineBackground: Antenatal corticosteroids improve newborn outcomes for preterm infants. However, predicting which women presenting for threatened preterm labor will have preterm infants is inaccurate, and many women receive antenatal corticosteroids but then go on to deliver at term. Objective: This study aimed to compare the short-term outcomes of infants born at term to women who received betamethasone for threatened preterm labor with infants who were not exposed to betamethasone in utero. Study design: We performed a retrospective cohort study of infants born at or after 37 weeks' gestational age to mothers diagnosed as having threatened preterm labor during pregnancy. The primary neonatal outcomes of interest included transient tachypnea of the newborn, neonatal intensive care unit admission, and small for gestational age and were evaluated for their association with betamethasone exposure while adjusting for covariates using multiple logistic regression. Results: Of 5330 women, 1459 women (27.5%) received betamethasone at a mean gestational age of 32.2±3.3 weeks. The mean age of women was 27±5.9 years and the mean gestational age at delivery was 38.9±1.1 weeks. Women receiving betamethasone had higher rates of maternal comorbidities (P<.001 for diabetes mellitus, asthma, and hypertensive disorder) and were more likely to self-identify as White (P=.022). Betamethasone-exposed neonates had increased rates of transient tachypnea of the newborn, neonatal intensive care unit admission, small for gestational age, hyperbilirubinemia, and hypoglycemia (all, P<.05). Controlling for maternal characteristics and gestational age at delivery, betamethasone exposure was not associated with a diagnosis of transient tachypnea of the newborn (adjusted odds ratio, 1.10; 95% confidence interval, 0.80-1.51), although it was associated with more neonatal intensive care unit admissions (adjusted odds ratio, 1.49; 95% confidence interval, 1.19-1.86) and higher odds of the baby being small for gestational age (adjusted odds ratio, 1.78; 95% confidence interval, 1.48-2.14). Conclusion: Compared with women evaluated for preterm labor who did not receive betamethasone, women receiving betamethasone had infants with higher rates of neonatal intensive care unit admission and small for gestational age. Although the benefits of betamethasone to infants born preterm are clear, there may be negative impacts for infants delivered at term.Item Are Newborn Outcomes Different for Term Babies Who Were Exposed to Antenatal Corticosteroids?(American Journal of Obstetrics and Gynecology, 2021-05-03) McKinzie, Alexandra; Yang, Ziyi; Teal, Evgenia; Daggy, Joanne K.; Tepper, Robert S.; Quinney, Sarah K.; Rhoads, Eli; Haneline, Laura S.; Haas, David M.; Obstetrics and Gynecology, School of MedicineBackground Antenatal corticosteroids improve newborn outcomes for preterm infants. However, predicting which women presenting for threatened preterm labor will have preterm infants is inaccurate and many women receive antenatal corticosteroids but then go on to deliver at term. Objective The purpose of this study was to compare the short-term outcomes of infants born at term to women who received betamethasone (BMZ) for threatened preterm labor to infants who were not exposed to BMZ in utero. Study Design We performed a retrospective cohort study of infants born at or after 37 weeks’ gestational age (GA) to mothers diagnosed with threatened preterm labor during pregnancy. The primary neonatal outcomes of interest included transient tachypnea of the newborn (TTN), neonatal intensive care unit (NICU) admission, and small for gestational age (SGA), and were evaluated for their association with BMZ exposure while adjusting for covariates using multiple logistic regression. Results Of 5330 women, 1459 (27.5%) women received BMZ at a mean GA of 32.2±3.3 weeks. The mean age of women was 27±5.9 years-old and the mean GA at delivery was 38.9±1.1 weeks. Women receiving BMZ had higher rates of maternal comorbidities (P<0.001 for diabetes, asthma, and hypertensive disorder) and were more likely to self-identify as white (P=0.022). BMZ-exposed neonates had increased rates of TTN, NICU admission, SGA, hyperbilirubinemia, and hypoglycemia (all P-values <0.05). Controlling for maternal characteristics and GA at delivery, BMZ exposure was not significantly associated with diagnosis of TTN (aOR 1.10, 95% CI 0.80-1.51), though it was associated with more NICU admissions (aOR 1.49, 95% CI 1.19-1.86) and higher odds of the baby being small for gestational age (SGA, aOR 1.78, 95%CI 1.48 to 2.14). Conclusions Compared to women evaluated for preterm labor that did not receive BMZ, women receiving BMZ had infants with higher rates of NICU admission and SGA. While the benefits of BMZ to infants born preterm are clear, there may be negative impacts for infants delivered at term.Item Are Selective Estrogen Receptor Beta Agonists Potential Therapeutics for Schizophrenia?(Oxford University Press, 2020-05-18) Breier, Alan; Liffick, Emily; Hummer, Tom; Vohs, Jennifer; Mehdiyoun, Nicole; Yang, Ziyi; Saykin, Andrew J.; McDonald, Brenna; Francis, Michael; Medicine, School of MedicineBackground Estrogen therapies, such as estradiol, have shown promise as therapeutics for schizophrenia; however, safety and tolerability concerns, including feminization effects in men and cancer and stroke risk in pre-menopausal women, may limit their broader use. Estradiol binds to both the estrogen alpha (ERA) and beta (ERB) receptors. ERB receptors appear not to mediate many of the concerning side effects of estrogen therapies. In addition, beta receptors have unique localization in cortical regions (i.e., hippocampus), and improve social behaviors and cognition in some animal models, which has led to interests in these compounds for testing in schizophrenia. To our knowledge, there have been no previous clinical trials of selective ERB agonists in schizophrenia. LY500307 is a highly selective agent for beta receptors without effects on estrogen alpha receptors when doses are constrained. Doses that are too high may engage alpha receptors but the alpha engaging threshold dose has not been fully determined in patient groups. The purpose of this dose-response study was to determine: ERB selectivity doses of LY500307 (i.e., without engaging alpha receptors); safety and tolerability; brain target engagement; and effects on cognition and symptoms. Methods A two-staged, double-blind, 8-week, adjunctive to APDs, adaptive phase 1b/2a trial design was conducted in men with schizophrenia (women were not included because of the lack of toxicology, safety, phase 1 and clinical data supporting use in this population). Three LY500307 doses and placebo were evaluated: 25 mg/day, 75 mg/day, and 150 mg/day. The primary markers for estrogen beta receptor selectivity was lack of effects on total testosterone levels (TT) and no feminization signs. Target engagement was assessed with an N-back working memory fMRI task and the electrophysiology measure mismatch negativity (MMN). Cognitive effects were assessed by the MCCB Composite score. Negative and total symptoms were assessed by the NSA-16 and PANSS, respectively. The primary analyses included all subjects and compared the slope from the three LY500307 dosing arms to the placebo slope in order to evaluate the dose responses. The linear mixed model with random intercept was employed and secondary analyses assessed differences between mean changes of the two higher dose arms combined (75 mg and 150 mg) versus placebo. Results Ninety-four patients were randomized across the placebo and three LY500307 dosing arms. There were no effects on plasma TT levels and no evidence of feminization, suggesting all doses were selective for the beta receptor. No significant adverse events were observed. There were no significant differences between the slopes of the three drug doses versus placebo on the brain target engagement variables (fMRI/N-back: F=0.24, p=0.868; MMN (Duration): F=1.08, p=0.358; MMN (Frequency): F=0.89, p=0.446) or on the cognitive/symptom measures (MCCB composite: F=0.87, p=0.458; NSA-16: F=1.79, p=0.148; and PANSS Total: F=0.69, p=0.558.) Secondary analyses also failed to show any significant effects of LY500307 versus placebo on any of the study variables. Discussion Conclusions: This study indicates that the ERB agonist LY500307 was selective, safe, and well tolerated in patients with schizophrenia. This selective ERB agonist, however, failed to demonstrate any significant effects on brain targets, cognition, negative and total symptoms. Potential issues related to dosing and characteristics of the patient population will be discussed. These data suggest that estrogen alpha receptor activation may be necessary to yield positive results in this patient population. Future studies are needed to confirm these findings.Item Association of severe malaria with cognitive and behavioural outcomes in low- and middle-income countries: a meta-analysis and systematic review(BMC, 2023-08-03) Ssemata, Andrew Sentoogo; Nakitende, Ann Jacquelline; Kizito, Simon; Thomas, Melissa R.; Islam, Sumaiya; Bangirana, Paul; Nakasujja, Noeline; Yang, Ziyi; Yu, Yunpeng; Tran, Tuan M.; John, Chandy C.; McHenry, Megan S.; Social and Behavioral Sciences, School of Public HealthBackground: Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs. Methods: Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group. Results: Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78). Conclusion: Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection.Item Characterization of the Rate of Aortic Dilation in Young Patients with Thoracic Aortic Aneurysm(Springer, 2021) Wheeler, Adam P.; Yang, Ziyi; Cordes, Timothy M.; Markham, Larry W.; Landis, Benjamin J.; Pediatrics, School of MedicineLongitudinal changes in aortic diameters of young patients with thoracic aortic aneurysm (TAA) have not been completely described, particularly over long periods of follow-up. This retrospective study sought to characterize the rates of proximal aortic dilation in young patients, identify risk factors for TAA progression, and evaluate the predictive utility of early echocardiographic follow-up. Inclusion criteria were: (1) TAA or TAA-predisposing genetic diagnosis, (2) age < 25 years at first echocardiogram, and (3) minimum of 5 years of echocardiographic follow-up. Proximal aortic diameters were measured by echocardiography and Z-scores calculated to index for body surface area. TAA severity was classified as no TAA (Z-score < 2), mild (Z-score 2 to 4), or at least moderate (Z-score > 4). Among 141 included patients, mean age at first echocardiogram was 7.3 ± 3.5 years. Mean follow-up duration was 9.8 ± 3.5 years. Fifty five patients had a genetic syndrome, and 38 of the non-syndromic patients had bicuspid aortic valve (BAV). The rate of aortic dilation was significantly higher at the ascending aorta than other aortic segments. BAV and age > 10 years at first echocardiogram were associated with increased rate of ascending aorta dilation. At the ascending aorta, over 25% of patients had categorical increase in TAA severity between first and last echocardiograms, and such patients demonstrated higher rate of dilation within their first 2 years of follow-up. These longitudinal findings highlight progressive ascending aorta dilation in young patients, which may worsen around adolescence. This may help determine timing of follow-up and target ages for clinical trials.Item Characterizing health care utilization following hospitalization for a traumatic brain injury: a retrospective cohort study(Taylor & Francis, 2021) Eliacin, Johanne; Yang, Ziyi; Kean, Jacob; Dixon, Brian E.; Psychiatry, School of MedicineObjective: The purpose of this study was to characterize health services utilization among individuals hospitalized with a traumatic brain injury (TBI) 1-year post-injury. Methods: Using a retrospective cohort design, adult patients (n = 32, 042) hospitalized with a traumatic brain injury between 2005 and 2014 were selected from a statewide traumatic brain injury registry. Data on health services utilization for 1-year post-injury were extracted from electronic medical and administrative records. Descriptive statistics and logistic regression were used to characterize the cohort and a subgroup of superutilizers of health services. Results: One year after traumatic brain injury, 56% of participants used emergency department services, 80% received inpatient services, and 93% utilized outpatient health services. Superutilizers had ≥3 emergency department visits, ≥3 inpatient admissions, or ≥26 outpatient visits 1-year post-injury. Twenty-six percent of participants were superutilizers of emergency department services, 30% of inpatient services, and 26% of outpatient services. Superutilizers contributed to 81% of emergency department visits, 70% of inpatient visits, and 60% of outpatient visits. Factors associated with being a superutilizer included sex, race, residence, and insurance type. Conclusions: Several patient characteristics and demographic factors influenced patients’ healthcare utilization post-TBI. Findings provide opportunities for developing targeted interventions to improve patients’ health and traumatic brain injury-related healthcare delivery.Item Community Engagement and Venue-Based Sampling in Adolescent Male Sexually Transmitted Infection Prevention Research(Elsevier, 2018-03) Ott, Mary A.; Moon, Julianne; Imburgia, Teresa M.; Yang, Ziyi; Tu, Wanzhu; Auerswald, Colette L.; Pediatrics, School of MedicineOBJECTIVES: Middle adolescent males are a difficult group to recruit for community sexually transmitted infection (STI) prevention research. We describe a process of community engagement, and venue-based sampling of 14-17-year-old adolescent males, and compare rates of STIs and STI risk behaviors by venue. METHODS: Community engagement consisted of (1) informational meetings with organizations; (2) participation in community meetings and events; (3) hiring community members as study personnel; and (4) an adolescent advisory board recruited from the community. Venues were identified and assessed at different times of the day and days of the week using a structured tool. At selected venues, males ages 14-17 years were invited to participate in a brief survey and provide a urine sample and an optional anal swab for DNA-based STI testing. RESULTS: Venues were assessed (n = 249), and 31 were selected for recruitment, including parks, apartment complexes, community events, entertainment venues, a community school, and community programs for LGBT (gay, lesbian, bisexual, transgender) and adjudicated youth. We enrolled 667 participants, average age 15.7 years. Participants reported high rates of sexual and STI risk behaviors, but had low rates of STIs. These rates differed by venue, with more structured venues recruiting youth reporting fewer STI risk behaviors and less structured venues within the highest STI prevalence zip code recruiting youth reporting more STI risk behaviors. CONCLUSION: Venue-based sampling is a feasible mechanism to target recruitment and enrollment adolescent males with high STI risk behaviors in community settings, with risk profiles varying by setting.Item Cultural Adaptation of the Bayley Scales of Infant and Toddler Development, 3rd Edition for use in Kenyan Children Aged 18–36 Months: A Psychometric Study(Elsevier, 2021) McHenry, Megan S.; Oyungu, Eren; Yang, Ziyi; Hines, Abbey C.; Ombitsa, Ananda R.; Vreeman, Rachel C.; Abubakar, Amina; Monahan, Patrick O.; Pediatrics, School of MedicineBackground: The Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) is frequently used in international child development research. No studies examine its psychometric properties when culturally adapted within the Kenyan context. Aims: To culturally adapt the Bayley-III for use in Kenya and evaluate its validity and reliability. Methods and procedures: Forward and backward translation, cognitive interviews, and a brief pilot of culturally adapted items were performed. This psychometric study was part of another study on children born to mothers with HIV in Eldoret, Kenya. One hundred seventy-two children aged 18-36 months were assessed for cognition, receptive/expressive communication, and fine/gross motor domains using the Bayley-III. Confirmatory factor analysis (CFA), inter-scale Pearson correlations, internal consistency, t-tests, and test-retest reliability were performed. Outcomes and results: The mean age of children was 22.8 (SD 4.5) months old; 52.7 % (n = 89) were male. CFA revealed that both two- and three-factor indices had good and comparable fit. Pearson correlations were high between fine motor and receptive communication (r >0.70). Internal consistency was very strong for all of the subtests, with Cronbach coefficient alpha scores ranging from 0.88 to 0.96. Known groups/convergent validity was confirmed with stunting and parental concern for delays. Test-retest reliability was good and did not differ substantially across groups. Conclusions and implications: The Kenyan adapted Bayley-III is a psychometrically acceptable tool to assess child development. The scaled and composite scores should not be used to define Kenyan developmental norms, but it can be useful for comparing groups within research settings.