Professional organizations recommend ultrasound as the initial diagnostic imaging modality for children with suspected nephrolithiasis. Computed tomography utilization for children with nephrolithiasis treated at freestanding children’s hospitals is common and varies substantially by hospital.

The high prevalence and regional variability of CT as the first imaging study for children with nephrolithiasis who presented to emergency departments, outpatient clinics, and hospitals throughout the United States indicate that current imaging practices deviate substantially from guidelines. (Read the full article)

Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalizations. Mortality rates associated with RSV hospitalizations are based on estimates from studies conducted decades ago. Accurate understanding of mortality is required for identifying high-risk infants and children.

Mortality associated with RSV is uncommon in the 21st century, with annual deaths far lower than previous estimates. The majority of deaths occurred in infants with complex chronic conditions or in those with life-threatening conditions in addition to RSV infection. (Read the full article)

Hospitalized pediatric patients are often exposed to many medications during an inpatient admission. Drug–drug interactions may increase the risk of developing medication-related adverse drug events, leading to serious clinical morbidity and mortality.

Exposure to "major" potential drug–drug interactions occurs in 41% of pediatric hospitalizations in children’s hospitals. One-half of all these exposures were due to less common specific drug pairs (≤3% of patients exposed per hospital day) and thus may be less clinically familiar. (Read the full article)

Family engagement in the care of hospitalized children may improve outcomes, including medication safety. Although family-centered rounds (FCRs) provide a venue for family engagement in care, how families use this venue to influence medication-related topics is unknown.

Most families initiated medication-related dialogue during FCRs, discussing inpatient and home medications. Topics raised were important for medication adherence and safety, even altering treatment plans. Findings suggest specific medication topics that health care team members can anticipate addressing during FCR. (Read the full article)

Menu labels depicting physical activity calorie equivalents may lead to ordering of fast food meals totaling fewer calories for adults. The effects of physical activity calorie equivalent labeling on parents’ fast food decisions for their children have not been examined.

Parents shown menus with any type of caloric content label may order fast food meals totaling fewer calories for their children. Menu labels showing physical activity equivalents may be more likely to influence parents to encourage their children to exercise. (Read the full article)

Current recommendations for the first outpatient visit for newborns are based on known health risks during the first week of life. Knowledge of the relationship between early well child visits and hospital readmissions may inform newborn health policy interventions.

Newborns who have a first well child visit within the recommended time period after hospital discharge are substantially less likely be readmitted. Obstacles to early follow-up should be addressed to reduce the risk of readmission in this population. (Read the full article)

Various clinical and demographic factors are associated with sudden infant death syndrome (SIDS), and an association between altitude of residence and SIDS has been questioned but not yet demonstrated in any large observational studies.

This study demonstrates an association between altitude and SIDS, with higher SIDS rates observed at high elevation (>8000 feet) than at the more moderate elevations (<6000 feet). (Read the full article)

An increasing number of children are unvaccinated at entry into public schools, potentially endangering children who cannot be vaccinated for medical reasons and threatening herd immunity. Voluntary exemptions from immunizations vary geographically and by parental characteristics.

We find that exemption behavior is highest in peripheral areas of cities and that specific types of student populations are associated with high exemption rates. Additionally, there is spatial overlap between clusters of high personal exemption and medical exemption populations. (Read the full article)

Historically, children with end-stage renal disease who initiated chronic dialysis during the first year of life were far less likely to survive or successfully receive a kidney transplant compared with those who initiated chronic dialysis at older ages.

In recent years, survival has improved markedly among children who initiate chronic peritoneal dialysis at <1 year of age. Among those infants who initiate dialysis after the neonatal period and later undergo kidney transplantation, graft survival has improved as well. (Read the full article)

Given the efforts to decrease the use of ionizing radiation in pediatric patients, there is significant variability in head computed tomography (CT) scan use in pediatric emergency departments for minor head trauma.

This study characterized variability in CT scan rates for all body regions in emergency department, observation, and inpatient encounters across 30 tertiary pediatric hospitals. Two-fold variation remained after case-mix adjustment, with higher volume hospitals having lower rates of CT scanning. (Read the full article)

The Newseum in Washington has just launched Decision 2012: Exploring Elections and the Media, an online resource for teaching about the presidential campaign and election.

Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.

Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.

Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.

Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes.

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 E. coli bloodstream infection isolates from Oxfordshire, UK, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity 23% (78/339)) but improved when genetic features associated with penicillinase hyper-production (e.g. promoter mutations, copy number estimates) were considered (sensitivity 82% (277/339); p<0.0001). Most discrepancies occurred in isolates with peri-breakpoint MICs. We investigated two potential causes; the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

The human diseases caused by the fungal pathogens Cryptococcus neoformans and C. gattii are associated with high indices of mortality, and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anti-cryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anti-cryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anti-cryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anti-cryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mice model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

Durlobactam (DUR, also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem/cilastatin (IMI/CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In Part A, subjects including an elderly cohort (DUR 1 g) received single ascending doses of DUR 0.25-8 g. In Part B, multiple ascending dose of DUR 0.25-2 g were administered every 6 hours (q6h) for 29 doses. In Parts C and D, the drug-drug interaction (DDI) potential, including safety, of DUR (1 g) with SUL (1 g) and/or IMI/CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI/CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated either alone or in combination with SUL and/or IMI/CIL. After single and multiple doses, DUR demonstrated linear dose proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug:drug interaction potential was identified between DUR and SUL and/or IMI/CIL. SUL-DUR, 1 g (of each component) administered q6h with a 3 hour IV infusion, is under development for the treatment of serious infections due to A. baumannii.

Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug-resistance to specific anti-influenza drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that compounds 4a/4d acted at the late phase of viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of up-regulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, our study pointed the optimization direction of nitazoxanide as anti-influenza drug, and discovered two novel-structured candidates 4a/4d with relatively broad-spectrum antiviral potential.

Global markets rallied on the back of optimism that most governments were gearing up to at least partially reopen their economies following lockdowns to prevent the spread of the coronavirus.

BACKGROUND:

Mexican-origin women breastfeed at similar rates as white women in the United States, yet they usually breastfeed for less time. In our study, we seek to identify differences in Mexican-origin women’s breastfeeding intentions, initiation, continuation, and supplementation across nativity and country-of-education groups.

Ahead of Matchday 7, UEFA.com looks at some obvious selections and some lesser-owned options.

Elizabeth Stringer Keefe, Becky Shiring, Katie Robinson, Dr. Sonny Magana and Dr. Monica Burns contribute their suggestions on using tech to differentiate instruction.

Andrea T. Cruz
Apr 8, 2020; 0:peds.2020-0834v2-e20200834
COMMENTARY

Cristiano Ronaldo's overhead kick for Real Madrid against his current club Juventus has been voted UEFA.com Goal of the Season.

Alejandro Hoberman
Jul 1, 1999; 104:79-86
ARTICLES

C. Michael Cotten
Jan 1, 2009; 123:58-66
ARTICLES

The IMpact-RSV Study Group
Sep 1, 1998; 102:531-537
ARTICLES

Get the latest Kindle Paperwhite plus a leather cover and power adapter for just $129.97. That's less than the cost of the Paperwhite on its own.

To help teachers remotely engage their students during the coronavirus crisis, Penn State’s Holocaust, Genocide and Human Rights Education Initiative has released its first set of free learning resources.

Ahead of Matchday 8, UEFA.com looks at some obvious #UCLfantasy selections and those who could cause a surprise.

• Football stars show how to practise skills without breaking safety rules – or windows!
• Federation raises funds for coronavirus and earthquake aid

040 - Inaugural Best Women’s Player in Europe Award launched

Source: www.youtube.com - Friday, May 08, 2020

Students and faculty members at Penn State Behrend's Black School of Business are contributing to and assessing a financial literacy curriculum that is being taught at nearly 400 high schools in eight states.

Most Pi projects run on Linux, so having some command-line chops makes the Pi much easier to work with. These commands can teach you a lot as you tinker.

Property experts weigh in on the Monetary Policy Committee of the SA Reserve Bank's decision to lower interest rates.

Construction work on FWJK's R800 million residential development known as 16 on Bree has topped out with the 36th floor having been cast.

The horse racing authority is pleading for a partial restart of the industry under Level 4 of the lockdown, warning that a prolonged suspension of activity could lead to massive financial impact and job losses.

Denmark overwhelmed Ireland to claim Europe's last FIFA World Cup berth after Sweden ousted Italy to follow Switzerland and Croatia through.

DOVER — Two Delaware families are becoming homeowners in central Dover with the purchase of single-family homes constructed by NCALL as part of the Restoring Central Dover initiative. NCALL, the Delaware State Housing Authority, elected officials and other partners and supporters celebrated the project today, part of a multi-pronged approach to homeownership and economic development […]

The north section of Lot Red A located between the Earth and Engineering Sciences Building and the West Campus Intramural Fields at University Park will permanently close beginning Monday, May 11. All vehicles, including University department vehicles, must be removed from this area by Sunday night, May 10.

Researchers in Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures and have devised a way to create plasma directly in liquids.

The majority of pediatric hospitalization costs are associated with the room; improvement projects that address room costs could have the most financial impact.

Internal rate of return: remember that candidates must be sifted through the funnies sieve first.

The Sustainable Growth table offers it a most intriguing set of rankings to mull.

The Delaware Department of Justice’s Family Division announced that a new targeting of child support absconders has resulted in location of individuals who collectively owe more than $1 million in child support payments in order for them to begin paying support to their families. Led by Deputy Attorney General Phyllis Scully, Special Investigator William McGillan, […]