Coxsackievirus A6 (CVA6) was identified as an important cause of "severe" hand, foot, and mouth disease (HFMD) during the 2011–2012 outbreak in North America. The atypical cutaneous features in this outbreak have not been well documented.

The cutaneous manifestations of CVA6-associated HFMD may be more extensive and variable than classic HFMD. Four distinct morphologies characterize this exanthem: (1) widespread vesiculobullous and erosive lesions, (2) "eczema coxsackium," (3) an eruption similar to Gianotti-Crosti, and (4) purpuric lesions. (Read the full article)

The incidence of plagiocephaly varies widely and is based on anecdotal evidence of increase in the number of referrals to specialty clinics. Five studies have produced varying results, indicating that the incidence of plagiocephaly ranges from 3.1% to 61.0%.

This is the first study to estimate the incidence of positional plagiocephaly using 4 community-based data collection sites in infants ranging from 7 to 12 weeks of age. The estimated incidence of positional plagiocephaly was found to be 46.6%. (Read the full article)

Brief periods of low oxygen saturation are common in infants while restrained in car safety seats. There is some evidence that an insert that allows the infant head to rest in a neutral position in sleep may reduce hypoxic episodes.

This randomized controlled study shows that the insert reduced numbers of obstructive apneas and the severity of desaturation events but did not significantly reduce the overall rate of moderate desaturations. (Read the full article)

Despite the existence of authoritative guidelines to assist primary care physicians in identifying and managing attention-deficit/hyperactivity disorder (ADHD), ample evidence demonstrates that they continue to diagnose and treat this disorder suboptimally.

The introduction of a clinical decision support module resulted in higher quality of care with respect to ADHD diagnosis including a prospect for higher quality of ADHD management in children. (Read the full article)

Over the past 10 years, children’s hospitals increasingly have established pediatric palliative care programs, but little is known about the prevalence of these programs or their geographic distribution, range of services offered, staff composition, or funding.

Among the 162 hospitals that responded to this survey (71.7% response rate), 69% have a pediatric palliative care program, with substantial variation across programs in terms of how they are staffed and funded and what services they provide. (Read the full article)

Although appendicitis is the most common surgical cause of abdominal pain in pediatrics, its diagnosis remains elusive. When evaluated independently, clinical scoring systems and ultrasonography have been shown to have low to moderate sensitivity in the diagnosis of appendicitis.

Our study evaluated the accuracy of a clinical practice guideline combining the Samuel’s pediatric appendicitis score and selective ultrasonography as the primary imaging modality for children with suspected appendicitis. Our clinical pathway demonstrated high sensitivity and specificity. (Read the full article)

Integrated or collaborative care intervention models have revealed gains in provider care processes and outcomes in adult, child, and adolescent populations with mental health disorders. However optimistic, conclusions are not definitive due to methodologic limitations and a dearth of studies.

This randomized trial provides further evidence for the efficacy of an on-site intervention (Doctor Office Collaborative Care) coordinated by care managers for children's behavior problems. The findings provide support for integrated behavioral health care using novel provider and caregiver outcomes. (Read the full article)

Children with attention-deficit/hyperactivity disorder (ADHD) have poorer academic and social functioning and more language problems than typically developing peers. However, it is unknown how language problems impact the academic and social functioning of these children.

Language problems are common in children with ADHD and are associated with markedly poorer academic functioning independent of ADHD symptom severity and comorbidities. There was little evidence that language problems were associated with poorer social functioning for children with ADHD. (Read the full article)

Inadequate nutrient intake can compromise a child’s nutritional status, which may affect immune function. Improving dietary intake via a follow-up formula may support appropriate immune responses and improve a child’s ability to resist infection.

Children who consumed an experimental follow-up formula had fewer episodes and shorter duration of acute respiratory infections, as well as less antibiotic treatment, and fewer days missed of day care due to illness. (Read the full article)

Participation in youth ice hockey is increasing. Players are prone to injury because of the nature of the game. Injury patterns vary based on age, gender, and degree of contact permitted.

This study adds an updated description of injuries sustained by youth ice hockey players and associated demographic patterns, with emphasis on seriously injured children. It also evaluates health care utilization and outcomes related to youth ice hockey injuries. (Read the full article)

The traditional process-focused approach to quality improvement has not remedied NICUs’ inconsistency in quality of care delivery across clinically important measures. Global measurement of quality may induce broad, systems-based improvement, but must be formally studied.

We present a systematically developed and robust composite indicator, the Baby-MONITOR, to assess the quality of care delivered to very low birth weight infants in the NICU setting. (Read the full article)

Predicting high-risk populations in congenital diaphragmatic hernia (CDH) can help target care strategies. Prediction rules for infants with CDH often lack validation, are aimed at a prenatal population, and are of limited generalizability. We cannot currently discriminate the highest risk neonates during the crucial period shortly after birth.

This clinical prediction rule was developed and validated on an international database. It discriminates patients and high, intermediate, and low risk of mortality; is easy to apply; and is generalizable to most infants with CDH. (Read the full article)

Research has shown that HIV-affected children face considerable threats to health and mental health. Few studies have investigated the effects of HIV on the health and well-being of HIV-negative children living with HIV-positive caregivers.

By comparing the prevalence of mental health problems and protective and risk factors among HIV-positive, HIV-affected, and HIV-unaffected children in Rwanda, this study demonstrates that the mental health of HIV-affected children requires policy and programmatic responses comparable to HIV-positive children. (Read the full article)

Numerous studies have demonstrated clinical benefits of medical emergency team (MET) implementation, including reductions in mortality, cardiac arrests, and critical deterioration events. No studies have evaluated the financial costs and benefits of METs.

The costs of operating an MET can plausibly be recouped with a modest reduction in critical deterioration events. Hospitals reimbursed with bundled payments could see real financial savings by reducing critical deterioration events with a MET. (Read the full article)

Cardiovascular risk begins in childhood. New clinical guidelines established a care strategy for lowering risks. Incorporation of guidelines into routine practice lags due to barriers related to knowledge and attitudes about guidelines, as well as behaviors of practitioners, patients, and clinical systems.

This study demonstrated that a multifaceted approach including tools, education, and support for changes in practice systems can accelerate the adoption of guidelines during routine pediatric well-child visits, compared with dissemination of the guidelines alone. (Read the full article)

Parental reduced antigen diphtheria-tetanus-acellular pertussis (Tdap) vaccination is difficult to implement, and empirical data on its impact is limited to a single hospital-based study in Texas, which found no reduction in infant pertussis hospitalization.

In New South Wales, Australia, a case-control study found both parents receiving Tdap ≥4 weeks before disease onset was associated with a significant reduction in risk of early infant pertussis and suggestive of persistent protection in subsequent pregnancies. (Read the full article)

Children who have attention-deficit/hyperactivity disorder (ADHD) attending clinical services have poorer outcomes in adolescence on a range of measures. However, it is unknown how early in development these impairments appear, particularly for community-ascertained samples.

At age 6 to 8 years, children in the community with ADHD have significantly poorer mental health, academic performance and social function compared with control children. Children who have impairing ADHD symptoms should be referred early for assessment and intervention. (Read the full article)

Pediatric Brain Injury Research Network investigators recently derived a highly sensitive clinical prediction rule for pediatric abusive head trauma (AHT).

The performance of this AHT screening tool has been validated. Four clinical variables, readily available at the time of admission, detect pediatric AHT with high sensitivity in intensive care settings. (Read the full article)

IP-10 is a novel immunologic marker for tuberculosis (TB) infection. It has been suggested that IP-10 may perform better in children compared with the QuantiFERON test, but only a few studies have investigated IP-10 for diagnosing active TB in children.

This study is the first to investigate IP-10 and QuantiFERON for diagnosing TB in children by using consensus classifications. Both IP-10 and QuantiFERON exhibited poor performance in children from a high-burden setting, and performance was especially compromised in young children. (Read the full article)

Adolescent relationship abuse (ARA) is prevalent in confidential clinic settings such as school health centers (SHCs) and is associated with poor health outcomes. No evidence-based interventions target reduction of ARA in the SHC setting.

This study provides the first evidence of the potential benefits of a brief provider-delivered universal education and counseling intervention in SHCs to address and prevent a major public health problem: ARA. (Read the full article)

Frequency of influenza vaccination is low, partially because of missed opportunities to vaccinate. Barriers to implementing successful influenza vaccination reminders in the electronic health record include alert fatigue and incomplete vaccination information due to scattered records.

A noninterruptive, immunization information system–linked influenza vaccination reminder can increase vaccination late in the winter when fewer vaccine doses are usually administered. Tailoring the reminder to clinicians’ needs can increase its use. (Read the full article)

Although pediatric professional guidelines emphasize addressing a child’s social environment in the context of well child care, it remains unclear whether screening for unmet basic needs at visits increases low-income families’ receipt of community-based resources.

This study demonstrates that systematically screening and referring for social determinants of health during primary care can lead to the receipt of more community resources for families. (Read the full article)

Exclusive breastfeeding until 6 months of an infant’s age is described as the safest, most powerful and cost-effective intervention to reduce infant morbidity and mortality globally. In developing countries, only ~25% of infants are exclusively breastfed for 6 months.

We developed a psycho-educational intervention combining education with techniques of cognitive-behavioral therapy, integrated it into the routine work of community health workers, which increased the rate and duration of exclusive breastfeeding until 6 months of an infant’s age. (Read the full article)

Asthma is heterogeneous and 40% to 70% of patients fail to achieve control with current treatment strategies. To delineate relevant subphenotypes of asthma, identify key factors, and test novel interventions, comprehensive repositories linking clinical, environmental, and biologic data are required.

This is the first statewide repository for inpatient pediatric asthma. The data collected will better define asthma phenotypes, identify care practices associated with the best health outcomes, and inform personalized care plans to reduce reutilization and readmission for pediatric asthma. (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)

Medical home transformation is led by practice-level assessment, but much of the evidence supporting the medical home derives from individual-level assessment based on parental perception. The association between these 2 levels of assessment is unknown.

Among Boston-area community health centers, there was no association between the individual- and practice-level assessments of the medical home. This highlights the need for studies supporting the child health benefits of medical home practice transformation. (Read the full article)

Sleep deprivation is a worldwide problem in adolescents. The effectiveness of sleep education in enhancing sleep knowledge with consequent modification of sleep habits remains uncertain, in view of small sample sizes and lack of control groups in previous studies.

This large-scale, cluster randomized controlled study found that a school-based sleep education program was effective in enhancing sleep knowledge and improving behavioral and mental health, but it had no significant impact on sleep duration or pattern among adolescents. (Read the full article)

Pediatric patients suffer higher mortality due to the shortage of transplantable organs. Factors influencing families’ donation decisions are similar for pediatric and adult patients. However, the general perception that families of pediatric patients are less willing to donate persists.

Communication emerged as a critical factor of family authorization, reinforcing its importance in the organ donation process. Patient age (ie, adult versus pediatric) was not predictive of family authorization. (Read the full article)

More than 200 million children <5 years are not reaching their developmental potential. Lack of stimulating caregiving is a major cause, and effective scalable interventions are needed. Integrating parenting with health services has been recommended, but there are few evaluations.

An innovative parenting intervention can be delivered at routine visits for primary health care, with benefits to child cognitive development and parenting knowledge. This approach using films, discussion, and practice has the potential for delivery at scale. (Read the full article)

The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. A recent study suggested a link between antibiotics and JIA but did not examine the potential for confounding from infections or the role of antibiotic timing.

Antibiotics were associated with newly diagnosed JIA in a dose- and time-dependent manner after adjusting for infection and other confounders. Antibiotics may play a role in the pathogenesis of JIA. (Read the full article)

The developer, Ndemic Creations, wants to remind people that Plague Inc. is just a game, not a scientific model. The game's popularity has skyrocketed amid the ongoing coronavirus outbreak, which has managed to spread to the US.

All posts from the past seven years on race & gender challenges - in one place!

All Classroom Q&A posts on race and gender challenges from the past eight years are described and linked to in this compilation post.

We travel to Latvia to find out about one of the fastest-growing youth tournaments in Europe.

Authorities unable or unwilling to face up to a reality that might reveal their own shortcomings and ineptitude, usually resort to pinpointing a scapegoat. This year, Covid-19 fits that bill, says Terry Bell.

La rechute est le risque majeur des pays post-conflit et l'une des principales raisons de cette rechute s'appelle la corruption.

L’indifférence internationale est un facteur aggravant pour les conflits dans les petits pays. Cependant, en ce qui concerne la République centrafricaine (RCA), le contexte est paradoxalement différent.

Los conflictos en los países pequeños suelen agravarse debido a la indiferencia internacional. Sin embargo, en el caso de la República Centroafricana (RCA), el problema es ligeramente distinto. Hay una importante presencia internacional en este Estado, pero los actores principales han decidido mantenerse al margen y esperar en vez de intervenir activamente en la crisis.

En Centrafrique, la course aux élections qui prévoit des scrutins présidentiel et législatif avant la fin de l’année est aussi irréaliste que dangereuse. Alors que le plan initial de la transition a complètement déraillé, l’obstination des internationaux, et plus particulièrement de la France, à faire voter les Centrafricains à l’ombre des groupes armés, avec une administration territoriale squelettique et des haines inter-communautaires tenaces ressemble plus à une fuite en avant qu’à un processus de transition accompli.

The United States, France, and the United Nations are falling into an all too familiar trap in the Central African Republic (CAR) of financing transition elections before armed militias have been disarmed and their communal hold broken. Exclusionary and botched elections could trigger another wave of violence and deepen the crisis.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC₅₀ of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log₁₀. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the current study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1 in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

Background: Intensive care unit (ICU) patients may experience ceftriaxone underexposure but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes amongst ICU patients without central nervous system (CNS) infection.

Methods: A retrospective study of ICU patients receiving intravenous, empiric ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 grams of ceftriaxone daily for ≥72 hours were included and categorized as receiving ceftriaxone 1 gram or 2 grams daily. The primary, composite outcome was treatment failure: inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving ceftriaxone 2 grams daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort.

Results: A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 gram and 2 grams daily, respectively (p=0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 gram dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio=0.190; 95% confidence interval: 0.059 – 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR 1.440, 95% CI 1.254 – 1.653) and creatinine clearance at 72 hours from ceftriaxone initiation (aOR 0.980, 95% CI (0.971 – 0.999).

Conclusions: Ceftriaxone 2 grams daily when used as appropriate antimicrobial coverage may be appropriate for ICU patients with lower mortality risk.

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.

Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUC_ELF:AUC_plasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia.

Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens.