Sleep disorders are common in children and adolescents and have a substantial negative impact on daily life and school performance. Long-term evaluations of the efficacy and safety of pharmacologic treatment options for sleep disorders are lacking in pediatric patients.

These 2 studies provide the first evaluation of the effectiveness and safety of eszopiclone in children and adolescents with insomnia associated with ADHD. Data presented here encompass longer-term (up to 1 year) pediatric exposure to eszopiclone. (Read the full article)

Little is known about how pediatricians communicate with overweight Latino children and their parents regarding overweight and obesity.

Findings suggest that many overweight Latino children and their parents do not receive direct communication that the child is overweight, weight-management plans, culturally relevant dietary recommendations, or follow-up visits. (Read the full article)

Preparticipation physical evaluations (PPEs) are considered necessary for a high standard of care for US scholastic athletes. However, important questions remain regarding consistency of implementation and content of cardiovascular screening practices among states.

Our results show that PPE policies are variable among US states, and adoption of current PPE-4 best practices is slow, demonstrating the need for nationwide PPE standardization. (Read the full article)

In 2009, only 58% of pediatricians were using electronic health records (EHRs), most of which were lacking pediatric functionality. The American Recovery and Reinvestment Act (ARRA) of 2009 accelerated the implementation of EHRs in pediatric offices.

The effects of ARRA have remained largely unmeasured in pediatrics. This study provides information on the prevalence and functionalities of EHRs, as well as physicians’ perceptions. (Read the full article)

Head Start, a federally funded preschool program for low-income US children, has been reported to have beneficial effects on developmental outcomes. The association of Head Start participation with changes in children’s BMI has not been examined.

Preschool-aged children with an unhealthy weight status who participated in Head Start had a significantly healthier BMI by kindergarten entry age than comparison children in a primary care health system (both those receiving and those not receiving Medicaid). (Read the full article)

Tapentadol is used in the treatment of chronic pain, specifically diabetic neuropathy. It has known action on the μ-opioid receptor leading to drowsiness and apneas. There is no published information on the effects of tapentadol in small children.

After an accidental overdose in a child, tapentadol may be expected to cause μ-opioid clinical effects similar to other opioids. While the opioid effects predominate sympathomimetic effects are also seen. The risk of respiratory depression and dyspnea should be acknowledged. (Read the full article)

Some parents choose to "spread out" the recommended vaccine schedule for their child by decreasing the number of simultaneous vaccines or delaying certain vaccines until an older age. Epidemiologic studies demonstrate increasing numbers of parents are choosing to delay vaccines.

We demonstrate that almost all providers encounter requests to spread out vaccines in a typical month and, despite concerns, increasing numbers are agreeing to do so. Providers report many strategies in response to requests but think few are effective. (Read the full article)

Concern exists about the ability of new general pediatricians to find jobs that match their career goals.

A large majority of new pediatricians secure positions consistent with their career goals and desired responsibilities. (Read the full article)

Youth drinking is associated with adult drinking. Alcohol policies can influence youth and adult drinking. However, it is unknown whether alcohol policies influence youth drinking patterns directly or through their effect on adult drinking.

Alcohol policies, including population-oriented policies, are protective for youth drinking. The effect of population-oriented policies may be mediated though effects on adults. These findings suggest that efforts to reduce youth drinking should rely on policies that address all age groups. (Read the full article)

Parental hesitancy about childhood vaccines is prevalent and related to delay or refusal of immunizations. Physicians are highly influential in parental vaccine decision-making, but may lack confidence in addressing parents’ vaccine concerns.

A physician-targeted communications intervention designed to reduce maternal vaccine hesitancy through the parent-physician relationship did not affect maternal hesitancy or physician confidence communicating with parents. Further research should determine the most effective approaches to addressing vaccine hesitancy. (Read the full article)

Simulation-based education is increasing but its use in pediatric emergency medicine (PEM) fellowships has not been recently documented. Previous studies identified barriers including equipment and space, but growth of simulation centers and equipment has been widespread.

Simulation is widely used in PEM fellowships, and current barriers include faculty and learner time, implementation of best practices in simulation; equipment is less significant. Future work should focus on curriculum and evaluation development, aligning with the milestones. (Read the full article)

Prophylactic vaccination of young women 16 to 26 years of age with the 9-valent human papillomavirus (HPV)–like particle (9vHPV) vaccine prevents infection and disease with vaccine HPV types.

These data support bridging the efficacy findings with 9vHPV vaccine in young women 16 to 26 years of age to girls and boys 9 to 15 years of age and implementation of gender-neutral HPV vaccination programs in preadolescents and adolescents. (Read the full article)

The US Preventive Services Task Force recommends primary care clinicians apply fluoride varnish to the teeth of all young children, but no studies have examined the effect of comprehensive preventive oral health services on children’s clinical oral health status.

Comprehensive preventive oral health services delivered by primary care clinicians can help improve the oral health of Medicaid-enrolled children, but more work is needed to link medical and dental offices to ensure the continuity of dental care for these children. (Read the full article)

Biotinidase deficiency (BD) might cause severe and permanent consequences. Cases detected through newborn screening and under treatment are shown to remain asymptomatic. However, some countries, including Spain, do not provide universal BD screening within their national newborn screening programs.

It provides a first estimate of the lifetime costs and health outcomes of a Spanish birth cohort with and without neonatal screening for BD. It shows that newborn screening for BD is likely to be a cost-effective use of resources. (Read the full article)

The routine childhood immunization schedule is crowded during the first 2 years, leading to deferred doses and limiting the addition of new vaccines. Combination vaccines can reduce the "shot burden" and improve coverage rates and timeliness.

Antibody response rates to antigens contained in an investigational hexavalent vaccine (DTaP5-IPV-Hib-HepB) were noninferior to licensed comparator vaccines when given as a 3-dose infant series. The safety profile was similar to control except for increased rates of mild-to-moderate, self-limited fever. (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)

Attention is a prerequisite for neurocognitive and behavioral functioning, having a crucial role in academic and social child development. Children with traumatic brain injury have pronounced deficits in attention, but the nature and consequences of these deficits remain unclear.

Lapses of attention represent a core attention deficit after pediatric mild traumatic brain injury with risk factors for complicated traumatic brain injury, or moderate/severe traumatic brain injury. Importantly, lapses of attention explain the relation between intelligence and parent-rated attention problems. (Read the full article)

Infants born very prematurely or with a very low birth weight are known to have an increased risk of attention-deficit/hyperactivity disorder (ADHD). Results concerning late preterm children are controversial and studies examining fetal growth represented by weight for gestational age are scarce.

We demonstrate that each declining week of gestation increases the risk of ADHD. Also, late preterm infants have an increased risk. Furthermore, as weight for gestational age becomes smaller than 1 SD below the mean, the risk of ADHD increases. (Read the full article)

Choosing career paths can be a difficult decision for residents contemplating fellowship training. Limited resources are available to residents to help guide their choices.

This article provides additional descriptions and insight into actual lifestyle and workplace environments for pediatric residents who choose fellowship training compared with those who do not. (Read the full article)

Many studies have suggested that autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are commonly co-occuring neurodevelopmental conditions.

In children with co-occurring ASD and ADHD, an initial ADHD diagnosis may be associated with delayed ASD diagnosis and a higher likelihood of ASD diagnosis older than 6 years of age. Clinicians should consider ASD when evaluating young children presenting with ADHD symptoms. (Read the full article)

Glucose-6-phosphate dehydrogenase deficiency remains a global as well as a North American burden for extreme hyperbilirubinemia and kernicterus and is often unpredictable during the first few days after birth. Newborn screening for this enzyme deficiency is not universally available but debated.

Point-of-care screening, using digital microfluidics, provides accurate, low blood volume, and affordable technology for rapid newborn glucose-6-phosphate dehydrogenase enzyme screening that could guide clinicians before infants’ discharge from well-child nurseries and meet existing American Academy of Pediatrics’ recommendations. (Read the full article)

Communication between parents and providers is an important driver of parent experience of care. The impact of nighttime communication, which has become increasingly relevant after changes in resident physician duty hours, on parent experience is unknown.

Parent communication with nighttime doctors and nurses, and parent perceptions of communication and teamwork between these providers, may be important drivers of parent experience. Efforts to improve nighttime communication, both with parents and between team members, may improve parent experience. (Read the full article)

The American Academy of Pediatrics discourages providers from dismissing families who refuse vaccines for their children, yet some providers continue to do so.

We show that ~1 in 5 pediatricians dismiss families who refuse vaccines, and there is significant regional variation in the practice. Dismissing families for refusing vaccines was also associated with stricter state nonmedical exemption policies. (Read the full article)

In a 5-4 decision, the Supreme Court sided with four iPhone owners who contend the company has been inflating the prices on the App Store. Current antitrust laws allow the plaintiffs to recover three times the amount of damages.

We offer a guide to the roles of the officials in futsal.

The approaching elections could be important steps toward reviving democracy in Chad, but only if President Idriss Déby opens political space for the opposition beforehand.

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.

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.

Gepotidacin, a triazaacenaphthylene bacterial type II topoisomerase inhibitor, is in development for treatment of uncomplicated urinary tract infection (uUTI). This Phase 2a study in female participants with uUTI evaluated the pharmacokinetics (primary objective), safety, and exploratory efficacy of gepotidacin. Eligible participants (N = 22) were confined to the clinic at baseline, received oral gepotidacin 1,500 mg twice daily for 5 days (on-therapy; Days 1 to 5), and returned to the clinic for test-of-cure (Days 10 to 13) and follow-up (Day 28±3). Pharmacokinetic, safety, clinical, and microbiological assessments were performed. Maximum plasma concentrations were observed approximately 1.5 to 2 hours postdose. Steady state was attained by Day 3. Urinary exposure over the dosing interval increased from 3,742 μg.h/ml (Day 1) to 5,973 μg.h/ml (Day 4), with trough concentrations of 322 to 352 μg/ml from Day 3 onward. Gepotidacin had an acceptable safety-risk profile with no treatment-limiting adverse events and no clinically relevant safety trends. Clinical success was achieved in 19 (86%) and 18 (82%) of 22 participants at test-of-cure and follow-up, respectively. Eight participants had a qualifying baseline uropathogen (growth; ≥10⁵ CFU/ml). A therapeutic (combined clinical and microbiological [no growth; <10³ CFU/ml]) successful response was achieved in 6 (75%) and 5 (63%) of 8 participants at test-of-cure and follow-up, respectively. Plasma area under the free-drug concentration-time curve over 24 hours at steady state divided by the MIC (fAUC_0-24/MIC) and urine AUC_0-24/MIC ranged from 6.99 to 90.5 and 1,292 to 121,698, respectively. Further evaluation of gepotidacin in uUTI is warranted. (NCT03568942)

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy.

A case of M. leprae rifampicin resistance after irregular anti-leprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampicin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).

Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.

Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).

Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).

Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

OBJECTIVES:

Infantile hemangiomas (IHs) are common; some cases require timely referral and treatment to prevent complications. We developed and validated a reliable instrument for timely and adequate referral of patients with IH to experts by nonexpert primary physicians.

BACKGROUND:

Current guidelines from the American Academy of Pediatrics recommend screening children for developmental problems by using a standardized screening tool and referring at-risk patients to early intervention (EI) or subspecialists. Adoption of guidelines has been gradual, with research showing many children still not being screened and referred.

An AI-powered digital assistant to take notes for you? It’s already happening in the workplace, but classroom note taking could prove harder to automate.

Two alumni and one community partner contribute clinical medicine and research experience during the pandemic

Russell B. Toomey
Oct 1, 2018; 142:e20174218-e20174218
ARTICLES

Millicent Collins
Aug 1, 2017; 140:e20160719-e20160719
CASE REPORTS

Rangers vice-chairman John Bennett has criticised the SPFL for their 'cynical tactics' over their labelling of the club's dossier as a "smoking gun" - and insists the issue is not merely Gers vs the governing body.

Partick Thistle have released, in full, a letter sent by the club to SPFL chiefs following the news that league reconstruction has been scrapped - confirming the Jags' relegation.

T. Michael O'Shea
Jul 1, 1999; 104:15-21
ARTICLES

Yong Y. Han
Dec 1, 2005; 116:1506-1512
ARTICLES

Mobicip gives you the basic tools you need to monitor your children's web and app activity, but the lack of sophisticated time- and location-tracking features hold it back.

Eight Penn State Health doctors have been named among the Pennsylvania Medical Society's "Top Physicians Under 40."

The spring season at Penn State College of Medicine is packed full of research presentations, awards and ceremonies. Since experts cannot predict when social distancing guidelines will be relaxed, College of Medicine leaders plan on celebrating many of these springtime celebrations virtually — including commencement.

Most states have raised their expectations for what constitutes proficiency on state math and reading tests in the last decade, according to a new study.

Within three weeks, a pandemic has completely changed the national landscape on testing. The U.S. Department of Education has now excused all 50 states and the District of Columbia from the requirement that they test all their students in math and English/language arts.