Recommended management of febrile neonates (≤28 days) includes blood, urine, and cerebrospinal fluid cultures with hospital admission for antibiotic therapy. No study has reported adherence to standard recommendations in the management of febrile neonates in US pediatric emergency departments.

There is wide variation in adherence to recommended management of febrile neonates. High rates of serious infections in admitted patients but low return rates for missed infections in discharged patients suggest additional studies needed to understand variation from current recommendations. (Read the full article)

Income inequality is positively associated with several adverse child health and well-being outcomes. There is no existing research investigating the relationship between income inequality and child maltreatment rates.

This study is the first to demonstrate that increases in income inequality are associated with increases in child maltreatment rates at the county level. (Read the full article)

Concussions in youth are a common injury evaluated in the emergency department (ED). Early recognition and active management of this mild traumatic brain injury are important to safe recovery. Tools to assess and manage concussion in the ED are lacking.

Acute Concussion Evaluation tools, modified for ED use, improved reported follow-up with primary care or concussion specialists and adherence to recommendations. Barriers to follow-up remain and the importance of ongoing outpatient management should be stressed. (Read the full article)

Medical devices approved for adults can be used to treat children despite the lack of rigorous evidence. In 2007, Congress passed the Pediatric Medical Device Safety and Improvement Act to stimulate pediatric device development.

Most pediatric devices approved since the legislative change have had limited premarket study in children, with pediatric patients representing <10% of trial participants. Postmarketing studies required by the US Food and Drug Administration also yielded limited additional pediatric data. (Read the full article)

Owing to genetic variability in its metabolism, codeine can lead to fatal toxicity or inadequate treatment in pediatric subpopulations and several guidelines have recommended against its use in children. Little is known about codeine prescribing for children in the United States.

There has been a small decline in pediatric codeine prescriptions overall in emergency departments, but no change in prescription for children who have cough or upper respiratory infection, despite professional recommendations against this practice. Substantial numbers of children are being prescribed codeine annually. (Read the full article)

Children who experience outpatient adverse drug events represent 0.5% of pediatric emergency department visits. The subset of children with complex chronic conditions often take multiple medications, but the incidence and severity of adverse drug events in these children is unknown.

Children with complex chronic conditions have a higher risk of emergency department visits related to adverse drug events, compared with other children. The implicated drugs with the highest rates include psychotropic agents, antimicrobial agents, anticonvulsants, hormones/steroids, and analgesics. (Read the full article)

Phototherapy effectively treats unconjugated hyperbilirubinemia. However, in resource-poor settings, functional phototherapy devices are often unavailable due to financial constraints or erratic electrical power availability.

Filtered-sunlight phototherapy could be a cost-effective option in resource-poor settings with abundant sunlight. (Read the full article)

Research in the aftermath of large-scale terrorist attacks shows that exposed children experience numerous negative psychological sequelae, including increased emotional difficulties, posttraumatic stress, and significant attack-related life disruptions.

Most research on terrorism-exposed youth examines large-scale terrorism. Limited work examines reactions to terrorism of the scope of the marathon attack, and the extraordinary manhunt and shelter-in-place warning was an unprecedented experience. Understanding adjustment after these events is critical. (Read the full article)

Previous studies have revealed that children in child care are frequently ill with mild illness and are unnecessarily excluded from child care at high rates.

Parent race/ethnicity, single parents, and work-related concerns are associated with increased emergent/urgent care use for a sick child excluded from child care, even for mild illnesses. (Read the full article)

Pediatricians need to treat overweight in early childhood. Family-based interventions in specialized clinics are efficacious in children age 8 years and older. Data regarding treatment of younger children are limited in specialty clinics and primary care.

This study shows that a 12-month family-based behavioral intervention in primary care is more efficacious compared with Control condition with a child-only focus. Weight outcome differences between Intervention and Control persist in children and parents after a 12-month follow-up. (Read the full article)

Neonatal narcotic abstinence syndrome (NAS) has become more prevalent in the United States. There is no strong evidence base for NAS treatment and thus no consensus regarding NAS management, including the best treatment drug or best taper strategy.

This study demonstrates that regardless of the initial treatment opioid chosen, use of a standard treatment protocol with stringent weaning guidelines reduces duration of opioid exposure and length of hospital stay for infants with NAS. (Read the full article)

Concerns as well as hopes regarding electronic games have led researchers to study the influence of games on children, yet studies to date have largely examined potential positive and negative effects in isolation and using samples of convenience.

Results from this nationally representative study of children 10 to 15 years indicated low levels of regular daily play related to better psychosocial adjustment, compared with no play, whereas the opposite was true for those engaging in high daily play. (Read the full article)

There is substantial variation in the medical care provided to pediatric patients across diverse clinical settings. This variation raises concerns about whether every patient is receiving optimal care and whether more standardized approaches around clinical decisions are needed.

We observed wide variation in admission rates for common pediatric conditions across US children’s hospitals. Our findings highlight the need for greater focus on the standardization of decisions regarding hospitalization of patients presenting to the emergency department. (Read the full article)

Pediatric primary care has undergone a cultural shift. Changes in electronic health records, certification requirements, and practice structure have left many physicians feeling too busy to participate in research. Practice-based research networks must adapt to fit the current climate.

Adding quality improvement activities that meet Maintenance of Certification Part 4 criteria to research study design adds value to a practice-based research protocol. This incentive meets the needs of busy physicians, and may help researchers meet study recruitment goals. (Read the full article)

Stimulant medications are indicated for treatment of childhood attention-deficit/hyperactivity disorder (ADHD), but there is concern that stimulants may negatively affect growth. However, no longitudinal, population-based studies have examined height into adulthood for childhood ADHD cases.

This longitudinal, population-based study shows that neither childhood ADHD itself nor treatment with stimulants is associated with significant deficits in height into adulthood. (Read the full article)

Partner violence victimization is associated with mental and behavioral health effects linked to weight gain. Childhood maltreatment is directly linked to obesity and associated with neuroanatomic and psychosocial changes, which heighten vulnerability to subsequent stressors.

This study finds that dating violence victimization is associated with greater increases in BMI from adolescence to young adulthood among women. Women with previous exposure to childhood sexual abuse are especially vulnerable to dating violence–related increases in BMI. (Read the full article)

Although frequent utilizers of emergency departments (EDs) are targeted for quality improvement initiatives across the United States, little is known about the health services these patients receive in the ED.

Eight percent of children account for 24% of ED visits and 31% of all costs. Frequent utilizers of pediatric EDs, especially infants without a chronic condition, are least likely to need medications, testing, and hospital admission during their ED visits. (Read the full article)

Various low-risk criteria have been developed to guide management of the febrile young infant (<90 days), but they differ in age criteria, recommendations, and implementation. Therefore, variation in care is likely but has not been previously studied.

There is wide variation in testing, treatment, and overall resource utilization in management of the febrile young infant across all 3 age groups: ≤28, 29 to 56, and 57 to 89 days. There may be opportunities to improve care variation without compromising outcomes. (Read the full article)

There are discrepancies regarding which treatment is best in clinical practice for children with parapneumonic empyema, with some authors favoring video-assisted thoracoscopy and others favoring intrapleural fibrinolytic agents.

This study is one of the few randomized clinical trials on this subject in children and the first multicenter trial. It exclusively included patients with septated empyema. Thoracoscopy and fibrinolysis with urokinase were equally effective for this condition. (Read the full article)

Migraine headaches are a common presenting complaint in emergency departments. Abortive treatment in this setting is not well studied, leading to considerable variation in treatment. The relationship between acute medications and emergency department revisits has not been studied.

Eighty-five percent of children with migraine are successfully discharged from the emergency department; only 1 in 18 children require a return visit. Prochlorperazine is associated with less revisits than metoclopramide, and diphenhydramine use is associated with increased risk of return visits. (Read the full article)

In adults, adverse drug events account for 5% to 25% of all hospital admissions and 12% of emergency department (ED) visits of which 50% to 70% are preventable. There remains a significant gap in our understanding of the magnitude and impact of medication-related ED visits in pediatrics.

This study is the largest and most rigorous study performed evaluating the impact of medication-related visits to the ED in pediatrics and provides important information regarding the magnitude of this problem in our health care system. (Read the full article)

Obstructive sleep apnea syndrome (OSAS) is associated with significant comorbidity: behavioral problems, sleepiness, and impaired quality of life. However, the utility of OSAS symptoms versus polysomnography in the prediction of comorbidities or response to treatment is not well known.

Among children with OSAS, the Pediatric Sleep Questionnaire, a well-validated, simple 1-page symptom inventory, predicts key adenotonsillectomy-responsive OSAS comorbidities and their improvement after adenotonsillectomy. In contrast, polysomnographic results do not offer similar predictive value. (Read the full article)

Noninvasive ventilation (NIV) reduced the need of intubation in preterm infants with RDS. However, randomized studies comparing nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure are still lacking.

The present study shows no differences in short-term outcomes between 2 different NIV strategies, nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure, in preterm infants for the initial treatment of RDS. (Read the full article)

Childhood bacteremia caused by vaccine-preventable organisms has substantially declined over the last decade. Recognition of bacteremia in children is difficult, and delayed administration of antibiotics is associated with poor outcomes. Adults with health care–associated Gram-negative bacteremia experience delays in receiving appropriate antibiotics.

Bacteremia in children presenting to the emergency department is increasingly health care associated and resistant to empirical antibiotics. These infections are associated with increased length of stay. Rates of Gram-negative bacteremia have increased, and children with Gram-negative bacteremia experience delayed antibiotic administration. (Read the full article)

The diversifying US population has led to the examination of workforce diversity and training. National data on diversity, inclusion, and cultural competency training have been previously collected but have been assessed only at the macro level of medicine.

This study assesses workforce diversity, inclusion, and cultural competency training in departments of pediatrics across the country and provides the first assessment of departmental efforts to improve diversity and inclusion and provide cultural competency training to trainees and faculty. (Read the full article)

Firearm violence is a leading cause of death among US youth aged 14 to 24. The emergency department is a key setting for interacting with high-risk assault-injured youth and remains an underused but important setting for violence prevention programs.

High-risk youth seeking emergency department care for assault have high rates of firearm violence over the subsequent 2 years. Higher severity substance use, combined with negative retaliatory attitudes and access to firearms, increases this risk for involvement with firearm violence. (Read the full article)

Mortality rates and health care expenditures are high among infants requiring surgery for necrotizing enterocolitis. The impact of different surgical managements on mortality remains equivocal. Adjusted economic differences for various surgical treatments may exist but have not been elucidated.

After performing a relatively large-scale, adjusted analysis of cost and mortality for surgical managements currently used for treating necrotizing enterocolitis, a cost-benefit for a particular surgical approach was demonstrated while accounting for comorbidities and group assignment bias. (Read the full article)

Otorrhea is common in children with tympanostomy tubes: annually, 2 of 3 children develop 1 or more episodes. Antibiotic-glucocorticoid eardrops are the most effective treatment in both the short- and long-term.

Treatment with antibiotic-glucocorticoid eardrops costs less than oral antibiotics and initial observation in children with tympanostomy tubes who develop otorrhea. Non–health care costs constitute a substantial proportion of the total costs of this condition. (Read the full article)

Self-harm behavior is a major public health problem and a leading cause of death in adolescents. The majority of patients who self-injure do not die, but they are at increased risk for a successful future suicide attempt.

Emergency department visits for self-inflicted injuries in adolescents increased from 2009 to 2012, whereas visits for self-inflicted firearm injuries decreased. The presence of any comorbid condition increased risk for self-harm, indicating that increased attempts at prevention may be warranted in these young people. (Read the full article)

Street youth demonstrate elevated mortality compared with the general adolescent and young adult population. Suicide is a leading cause of death among street youth. Many street youth have experienced childhood maltreatment, including abuse and neglect.

In this prospective cohort of street youth, self-reported attempted suicide and history of childhood maltreatment were common. Individuals who experienced childhood physical abuse, emotional abuse, or emotional neglect were at highest risk of attempting suicide. (Read the full article)

Increasing percentages of youth are living with chronic medical conditions. Although adolescents face peak risks for onset and intensification of alcohol and marijuana use, we know little about these behaviors and their associations with treatment adherence among chronically ill youth.

This study quantifies alcohol and marijuana use behaviors among a heterogeneous sample of chronically ill youth in aggregate and by condition, and measures associations between alcohol use/binge drinking and knowledge about alcohol interactions with medications/laboratory tests and also treatment nonadherence. (Read the full article)

Unsupervised medication exposures increased during the previous decade, despite child-resistant packaging and caregiver education. To achieve the Healthy People 2020 objective of reducing emergency department visits for unintentional pediatric medication overdoses, targeted interventions including improved safety packaging may be needed.

Since 2010, emergency department visits for unsupervised medication exposures started to decrease. Most visits involved solid dose medications, typically for adult use. Most liquid medication exposure visits involved 4 over-the-counter pediatric products and may be more readily amenable for interventions. (Read the full article)

Tricycle riding is a common activity in children. In calendar year 2012, tricycle accidents were the most common cause of reported toy-related deaths in children. Little research has been conducted regarding tricycle-related injuries and how to counsel parents appropriately.

This study uses nationally representative data to investigate various characteristics of tricycle-related injuries in children to better counsel parents. This study highlights the importance of helmet and elbow pad use and parental supervision. (Read the full article)

Strictly-defined pediatric bipolar I disorder (BP-I) is a serious condition. Although lithium is a benchmark treatment and has shown effectiveness in adults for decades, no definitive efficacy or long-term safety studies had been performed in pediatric patients with BP-I.

This study provides evidence to support the efficacy of lithium in the acute treatment of youths with BP-I who are currently in a manic or mixed state. Lithium had an adverse effect profile that was acceptable for most patients. (Read the full article)

Many families share genetic cancer risk information with their children, and some parents and providers believe BRCA1/2 testing should be permitted in adolescence. The psychosocial effects and impact on health and risk behaviors of this knowledge is unknown.

In our cohort of 869 mother-daughter pairs, we found no differences in general adjustment, but 10- to 13-year-old girls with breast cancer family histories reported higher breast cancer–specific distress and perceived breast cancer risk. Mother distress was associated with daughter distress. (Read the full article)

National guidelines recommend testing and prophylaxis for chlamydia, gonorrhea, and pregnancy for adolescent sexual assault victims. Little is known about rates of testing and prophylaxis in adolescent victims of sexual assault evaluated in pediatric emergency departments.

There is significant variation in testing and prophylaxis practices in the pediatric emergency department evaluation of adolescent victims of sexual assault. Adolescents cared for in emergency departments with clinical pathways are more likely to receive recommended prophylaxis. (Read the full article)

Source: www.cnn.com - Saturday, May 09, 2020
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Texas has become the first state to have its "alternate assessment aligned to modified academic-achievement standards" pass the U.S. Department of Education's peer-review process.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, an early step in the conserved glycosylphosphotidyl inositol (GPI) post-translational modification pathway of surface proteins in eukaryotic cells. Inhibition of inositol acylation by MGX results in pleiotropic effects including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some strains of Mucorales. Here we assessed the in vivo activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two Rhizopus arrhizus strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-live of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 post infection when compared to placebo. In addition, administration of fosmanogepix resulted in a 1-2 log reduction in both lung and kidney fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first in class treatment for invasive mucormycosis.

Telacebec (Q203) is a new anti-tubercular drug with extremely potent activity against Mycobacterium ulcerans. Here, we explored the treatment-shortening potential of Q203 alone or in combination with rifampin (RIF) in a mouse footpad infection model. The first study compared Q203 at 5 and 10 mg/kg doses alone and with rifampin. Q203 alone rendered most mouse footpads culture-negative in 2 weeks. Combining Q203 with rifampin resulted in relapse-free cure 24 weeks after completing 2 weeks of treatment, compared to a 25% relapse rate in mice receiving RIF+clarithromycin, the current standard of care, for 4 weeks.

The second study explored the dose-ranging activity of Q203 alone and with RIF, including the extended activity of Q203 after treatment discontinuation. The bactericidal activity of Q203 persisted for ≥ 4 weeks beyond the last dose. All mice receiving just 1 week of Q203 at 2-10 mg/kg were culture-negative 4 weeks after stopping treatment. Mice receiving 2 weeks of Q203 at 0.5, 2 and 10 mg/kg were culture-negative 4 weeks after treatment. RIF did not increase the efficacy of Q203. A pharmacokinetics sub-study revealed that Q203 doses of 2-10 mg/kg in mice produce plasma concentrations similar to those produced by 100-300 mg doses in humans, with no adverse effect of RIF on Q203 concentrations.

These results indicate the extraordinary potential of Q203 to reduce the duration of treatment necessary for cure to ≤ 1 week (or 5 doses of 2-10 mg/kg) in our mouse footpad infection model and warrant further evaluation of Q203 in clinical trials.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC_50/90 32/64 μg/mL; E. faecium MIC_50/90 64/128 μg/mL). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log₁₀ CFU/mL; E. faecalis 8.0 ± 1.0 log₁₀ CFU/mL). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and two-doses given daily with low urinary exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log₁₀ kill from the starting inoculum compared with E. faecium. The fAUC_0-72/MIC and f%T > MIC_0-72 for E. faecalis was 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC post-exposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log₁₀ kill) in the majority of isolates.