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

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

Evaluation of the Impact of Different Management Methods on Tetranychus urticae (Acari: Tetranychidae) and Their Predators in Citrus Orchards

To evaluate the effectiveness of eco-friendly treatments based on detergents classified as non-hazardous and black soap on the pest Tetranychus urticae Koch 1836, and their predators (Euseius stipulatus Athias-Henriot, 1960, Typhlodromus sp., Phytoseiulus persimilis Athias-Henriot, 1957), different treatments were applied to citrus orchards planted with Valencia late (Orange) in the Mechraa Belksiri region of Morocco (T0 = control experiment; T1 = spirodiclofen 0.5 L/Ha; T2 = 125 L/Ha (5%) of black soap; T3 = detergent; 4 L/Ha of Oni product + 2 L/Ha of Tide product). The results obtained during the whole monitoring period indicated that the three treatments used, namely spirodiclofen, black soap, and detergents, ensured a reduction in the rate of population of the pest T. urticae compared to the untreated plot. In the untreated plot, the average was 45.01 A± 4.90 mobile forms, while the plot treated with spirodiclofen it was only 21.10 C ± 2.71, the black soap 31.49 B ± 3.35, and in the plot treated with detergents, the average was similar to that obtained by spirodiclofen (22.90 C ± 2.18). On the predators (E. stipulatus, P. persimilis, and Typhlodropmus sp.), the black soap and the treatment with detergents were less harmful compared to the chemical spirodiclofen

Evaluation of the Impact of Different Management Methods on Tetranychus urticae (Acari: Tetranychidae) and Their Predators in Citrus Orchards

To evaluate the effectiveness of eco-friendly treatments based on detergents classified as non-hazardous and black soap on the pest Tetranychus urticae Koch 1836, and their predators (Euseius stipulatus Athias-Henriot, 1960, Typhlodromus sp., Phytoseiulus persimilis Athias-Henriot, 1957), different treatments were applied to citrus orchards planted with Valencia late (Orange) in the Mechraa Belksiri region of Morocco (T0 = control experiment; T1 = spirodiclofen 0.5 L/Ha; T2 = 125 L/Ha (5%) of black soap; T3 = detergent; 4 L/Ha of Oni product + 2 L/Ha of Tide product). The results obtained during the whole monitoring period indicated that the three treatments used, namely spirodiclofen, black soap, and detergents, ensured a reduction in the rate of population of the pest T. urticae compared to the untreated plot. In the untreated plot, the average was 45.01 A± 4.90 mobile forms, while the plot treated with spirodiclofen it was only 21.10 C ± 2.71, the black soap 31.49 B ± 3.35, and in the plot treated with detergents, the average was similar to that obtained by spirodiclofen (22.90 C ± 2.18). On the predators (E. stipulatus, P. persimilis, and Typhlodropmus sp.), the black soap and the treatment with detergents were less harmful compared to the chemical spirodiclofen

Implementation of Digital Health Technology at Academic Medical Centers in Saudi Arabia

Academic Medical Centers (AMCs) in Saudi Arabia are dedicated to providing high-quality patient care and promoting the health and wellbeing of its citizens. Additionally, they provide medical education and conduct research in a wide range of clinical disciplines. A recent global trend in academic hospitals with mandates similar to those in Saudi Arabia is that they have started utilizing digital health technology in a bid to increase efficiency and improve the quality of patient care. This paper takes the position that such digital health technologies should also be utilized in AMC settings in Saudi Arabia. Electronic health records (EHRs), smartphones, video-imaging technologies, virtual desktop infrastructures, mobile EHR access, and smart-beds can help AMCs serve patients more effectively. Rural people can be connected to consultants at AMCs using these technologies using virtual self-care tools. Validation of new digital health devices can be performed in collaboration with digital health partners and serve to enrich the knowledge of medical students in the area of digital health. This review aims to draw the attention of stakeholders to the need to implement digital health technology in AMCs in Saudi Arabia and help improve the quality of healthcare

Ultrastructure of antennal sensillae of the samsum ant, Pachycondyla sennaarensis (Hymenoptera: Formicidae)

Black ant (Samsum), Pachycodyla sennarrensis, stings and injects venom and inflicts allergy (a rare clinical problem) due to its local and systemic reaction, which is considered as a health hazard amongst Saudi society. Thus, black ant is a source of serious concern for the government and experts as well.  Ultramorphological variations, distribution, differential sensillae counts (DSC) and total sensillae counts (TSC), were identified and estimated as a complementary part of the peripheral nervous system on the antennae of worker samsum ant, P. sennarrensis in order to understand its behavioral ecology. Based on scanning electron micrographs, four types of sensillae constituted with three trichoid types, which is an abundant form with a high distribution density at the apex, but a low density at subsequent proximal flagellomere of the antenna and a placoid type of sensillae (a rare form mostly found in the middle of the flagellum, that is, on the 4th, 5th and 6th flagellomere) were categorised. It is documented that nonporous trichoid type of sensillae are mechanoreceptors and thermoreceptors, whereas, the placoid types are olfactory receptors. Present findings in an indigenous species in Saudi Arabia may help in understanding the ecological behaviour of the ant, which subsequently may form the basis in producing its effective control measure in future.Key words: Samsum ants, Pachycondyla sennarrensis, ultrastructure, antenna, sensillae

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology