Sickle Cell Disease Treatment with Arginine Therapy (STArT): Study protocol for a phase 3 randomized controlled trial

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant\u27s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. DISCUSSION: Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children. TRIAL REGISTRATION: The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354)

Impact of SARS-CoV-2 infection on the association between laboratory tests and severe outcomes among hospitalized children

BACKGROUND: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. METHODS: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. RESULTS: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin \u3e500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count \u3c1.0 × 10 CONCLUSIONS: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative

An assessment of residents’ and fellows’ personal finance literacy: An unmet medical education need

Objectives: This study aimed to assess residents' and fellows' knowledge of finance principles that may affect their personal financial health. Methods: A cross-sectional, anonymous, web-based survey was administered to a convenience sample of residents and fellows at two academic medical centers. Respondents answered 20 questions on personal finance and 28 questions about their own financial planning, attitudes, and debt. Questions regarding satisfaction with one's financial condition and investment-risk tolerance used a 10-point Likert scale (1=lowest, 10=highest). Of 2,010 trainees, 422 (21%) responded (median age 30 years; interquartile range, 28-33). Results: The mean quiz score was 52.0% (SD = 19.1). Of 299 (71%) respondents with student loan debt, 144 (48%) owed over $200,000. Many respondents had other debt, including 86 (21$25,000. Respondents' mean satisfaction with their current personal financial condition was 4.8 (SD = 2.5) and investment-risk tolerance was 5.3 (SD = 2.3). Indebted trainees reported lower satisfaction than trainees without debt (4.4 vs. 6.2, F (1,419) = 41.57, p < .001). Knowledge was moderately correlated with investment-risk tolerance (r=0.41, p < .001), and weakly correlated with satisfaction with financial status (r=0.23, p < .001). Conclusions: Residents and fellows had low financial literacy and investment-risk tolerance, high debt, and deficits in their financial preparedness. Adding personal financial education to the medical education curriculum would benefit trainees. Providing education in areas such as budgeting, estate planning, investment strategies, and retirement planning early in training can offer significant long-term benefits.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Outcomes of SARS-CoV-2-positive youths tested in emergency departments: The global PERN-COVID-19 study

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (\u3e99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to \u3c10 years vs \u3c1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to \u3c18 years vs \u3c1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions

Impact of Risk-based Sexually Transmitted Infection Screening in the Emergency Department

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents. METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing recommendations. Patient answers and testing recommendations were integrated in real-time into the electronic health record. Patients who tested positive received treatment according to our standard-of-care practices. All patients 15-21 years of age were asked to complete this on an opt-out basis, regardless of the reason for their ED visit. Exclusions included those unable to independently use a tablet, severe illness, sexual assault, or non-English speaking. Our primary outcome was to describe STI-testing recommendations and test results among ACASI participants. We also compared STI testing between ACASI participants and those who were eligible but did not use it. RESULTS: In the first 13 months, 28.9% (1788/6194) of eligible adolescents completed the ACASI and 44.2% (321/790) accepted recommended STI testing. The mean age of participants was 16.6 ± 1.3 years, with 65.4% (1169) being female. Gonorrhea/chlamydia testing was significantly higher among participants vs. non-participants (20.1% [359/1788] vs 4.8% [212/4406]; p \u3c 0.0001). The proportion of positive STI tests was similar between the two groups: 24.8% (89/359) vs. 24.5% (52/212; p = 0.94) were positive for chlamydia and/or gonorrhea, while 0.6% (2/354) participants vs. 0% non-participants (p \u3e 0.99) were positive for HIV. Among participants whose chief complaints were unlikely to be related to STIs but accepted recommended testing, 20.9% (37/177) were positive for gonorrhea or chlamydia. CONCLUSIONS: Our program facilitated STI testing in the ED and identified many adolescents with STIs, even when their ED complaint was for unrelated reasons. More rigorous implementation is needed to determine the impact of deployment of ACASI to all eligible adolescents and addressing barriers to accepting STI testing recommendations

Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity

Steroid receptor RNA activator gene (SRA1) emerges as a player in pathophysiological responses of adipose tissue (AT) in metabolic disorders such as obesity and type 2 diabetes (T2D). We previously showed association of the AT SRA1 expression with inflammatory cytokines/chemokines involved in metabolic derangement. However, the relationship between altered adipose expression of SRA1 and the innate immune Toll-like receptors (TLRs) as players in nutrient sensing and metabolic inflammation as well as their downstream signaling partners, including interferon regulatory factors (IRFs), remains elusive. Herein, we investigated the association of AT SRA1 expression with TLRs, IRFs, and other TLR-downstream signaling mediators in a cohort of 108 individuals, classified based on their body mass index (BMI) as persons with normal-weight (N = 12), overweight (N = 32), and obesity (N = 64), including 55 with and 53 without T2D. The gene expression of SRA1, TLRs-2,3,4,7,8,9,10 and their downstream signaling mediators including IRFs-3,4,5, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), and nuclear factor-κB (NF-κB) were determined using qRT-PCR and SRA1 protein expression was determined by immunohistochemistry. AT SRA1 transcripts’ expression was significantly correlated with TLRs-3,4,7, MyD88, NF-κB, and IRF5 expression in individuals with T2D, while it associated with TLR9 and TRAF6 expression in all individuals, with/without T2D. SRA1 expression associated with TLR2, IRAK1, and IRF3 expression only in individuals with obesity, regardless of diabetes status. Furthermore, TLR3/TLR7/IRAK1 and TLR3/TLR9 were identified as independent predictors of AT SRA1 expression in individuals with obesity and T2D, respectively. Overall, our data demonstrate a direct association between the AT SRA1 expression and the TLRs together with their downstream signaling partners and IRFs in individuals with obesity and/or T2D

A Predictive Model for Steady State Ozone Concentration at an Urban-Coastal Site

Ground level ozone (O3) plays an important role in controlling the oxidation budget in the boundary layer and thus affects the environment and causes severe health disorders. Ozone gas, being one of the well-known greenhouse gases, although present in small quantities, contributes to global warming. In this study, we present a predictive model for the steady-state ozone concentrations during daytime (13:00–17:00) and nighttime (01:00–05:00) at an urban coastal site. The model is based on a modified approach of the null cycle of O3 and NOx and was evaluated against a one-year data-base of O3 and nitrogen oxides (NO and NO2) measured at an urban coastal site in Jeddah, on the west coast of Saudi Arabia. The model for daytime concentrations was found to be linearly dependent on the concentration ratio of NO2 to NO whereas that for the nighttime period was suggested to be inversely proportional to NO2 concentrations. Knowing that reactions involved in tropospheric O3 formation are very complex, this proposed model provides reasonable predictions for the daytime and nighttime concentrations. Since the current description of the model is solely based on the null cycle of O3 and NOx, other precursors could be considered in future development of this model. This study will serve as basis for future studies that might introduce informing strategies to control ground level O3 concentrations, as well as its precursors’ emissions

A Predictive Model for Steady State Ozone Concentration at an Urban-Coastal Site

Ground level ozone (O-3) plays an important role in controlling the oxidation budget in the boundary layer and thus affects the environment and causes severe health disorders. Ozone gas, being one of the well-known greenhouse gases, although present in small quantities, contributes to global warming. In this study, we present a predictive model for the steady-state ozone concentrations during daytime (13:00-17:00) and nighttime (01:00-05:00) at an urban coastal site. The model is based on a modified approach of the null cycle of O-3 and NOx and was evaluated against a one-year data-base of O-3 and nitrogen oxides (NO and NO2) measured at an urban coastal site in Jeddah, on the west coast of Saudi Arabia. The model for daytime concentrations was found to be linearly dependent on the concentration ratio of NO2 to NO whereas that for the nighttime period was suggested to be inversely proportional to NO2 concentrations. Knowing that reactions involved in tropospheric O-3 formation are very complex, this proposed model provides reasonable predictions for the daytime and nighttime concentrations. Since the current description of the model is solely based on the null cycle of O-3 and NOx, other precursors could be considered in future development of this model. This study will serve as basis for future studies that might introduce informing strategies to control ground level O-3 concentrations, as well as its precursors' emissions.Peer reviewe

A Predictive Model for Steady State Ozone Concentration at an Urban-Coastal Site

Ground level ozone (O3) plays an important role in controlling the oxidation budget in the boundary layer and thus affects the environment and causes severe health disorders. Ozone gas, being one of the well-known greenhouse gases, although present in small quantities, contributes to global warming. In this study, we present a predictive model for the steady-state ozone concentrations during daytime (13:00–17:00) and nighttime (01:00–05:00) at an urban coastal site. The model is based on a modified approach of the null cycle of O3 and NOx and was evaluated against a one-year data-base of O3 and nitrogen oxides (NO and NO2) measured at an urban coastal site in Jeddah, on the west coast of Saudi Arabia. The model for daytime concentrations was found to be linearly dependent on the concentration ratio of NO2 to NO whereas that for the nighttime period was suggested to be inversely proportional to NO2 concentrations. Knowing that reactions involved in tropospheric O3 formation are very complex, this proposed model provides reasonable predictions for the daytime and nighttime concentrations. Since the current description of the model is solely based on the null cycle of O3 and NOx, other precursors could be considered in future development of this model. This study will serve as basis for future studies that might introduce informing strategies to control ground level O3 concentrations, as well as its precursors’ emissions