Isotretinoin is the most effective acne therapy available, but has the potential for a number of adverse side effects, including transaminitis. The iPLEDGE isotretinoin program recommends avoiding some herbals and supplements due to potential side effects. However, little is known about the effects of protein supplements on the liver, particularly in patients taking isotretinoin. We designed a retrospective chart review to evaluate the symptoms, diagnosis, treatment, and outcome of patients on or preparing to take isotretinoin therapy who were concurrently ingesting protein or herbal supplementation and who developed transaminitis. In 100% (8/8) of cases, dietary supplementation was determined to be at least a possible cause of elevated liver transaminases. In 75% (6/8) of cases, dietary supplement appears to be the most likely cause at some point in their evaluation. Most of our patients’ elevations in aspartate aminotransferase and/or alanine aminotransferase were likely caused by supplementation with protein, creatine, or herbal extracts, rather than prescribed isotretinoin or tetracycline antibiotics for acne. Hence, dietary supplementation may cause liver function abnormalities. As supplement usage appears common in teenagers, clinicians should consider counseling their patients to avoid these products, particularly when prescribing known hepatotoxic drugs.
Neonatal clitoromegaly is mainly attributed to in utero androgen exposure secondary to congenital adrenal hyperplasia. We report on 2 extremely premature girls with clitoromegaly, increased androgen levels, no salt wasting syndrome, and ovarian cyst. In case 1, the cyst liquid was aspired during ovarian hernia surgery and revealed high androgen levels. After aspiration, serum androgen levels decreased, as did clitoral size. In case 2, an ovarian cyst was seen on pelvic ultrasound. Aspiration was not indicated. The cyst regressed spontaneously on iterative pelvic ultrasounds, and her clitoromegaly decreased. Case 1 demonstrates the ovarian origin of this transient virilization. Cyst formation seems to be linked to the physiologic maturation of the hypothalamic-pituitary-ovarian axis. Thirteen cases of clitoromegaly with hyperandrogenism, without salt wasting syndrome, have been reported in extremely premature infants. In the context of clitoromegaly, we recommend ruling out in utero androgen exposure, adrenal hyperandrogenism, and disorders of sex development. We further recommend affirming hyperandrogenism by androgen assay and confirming ovarian origin with gonadotrophin assays and pelvic ultrasound. Drug therapy abstention and clinical and ultrasound monitoring are recommended because spontaneous regression of clitoral hypertrophy seems to be the most common outcome in the literature, as it was in our 2 observations.
Etiologies for childhood-onset diffuse joint contractures encompass a large group of inherited disorders and acquired diseases, in particular a subtype of juvenile idiopathic arthritis called "dry polyarthritis," dermatomyositis, and systemic sclerosis. We report on 2 boys, aged 5 and 8 years, who developed acquired symmetric painless joint contractures preceding the development of superficial plaques of morphea by 7 to 13 months. There was no other clinical involvement, biological inflammation, or autoantibodies. No urinary mucopolysaccharidosis was seen. In both patients, wrist MRI showed no joint effusion, no bone erosion, and no or mild synovial thickening with slight enhancement after gadolinium infusion. One patient underwent a synovial biopsy, which showed dense fibrosis with a sparse inflammatory infiltrate, similar to the pathologic pattern observed in the skin biopsy. With methotrexate and systemic steroids, joint contractures slowly improved in the first patient and remained stable in the second. These 2 cases suggest that fibrous synovitis should be considered in children with acquired diffuse, symmetric, painless contractures and without elevation of acute-phase reactants, even in the absence of cutaneous manifestations. Articular MRI with gadolinium and careful cutaneous examination at onset and during follow-up should provide clues for diagnosing this entity.
Patients who are diagnosed with Brugada syndrome (BS) usually experience sudden cardiac arrest (SCA) and arrhythmia when they have a high fever, consume alcohol, and, more frequently, during their night sleep. In some rare cases, an SCA can be seen depending on a possible vagal stimulus, such as eating a large bite of food. We describe a 9-year-old patient who had a sudden cardiac attack while he was eating a large hot dog. After successful resuscitation, a suspicious ST elevation in V2 was seen in his electrocardiographic evaluation. He was diagnosed with BS after the ajmaline test and an implantable cardioverter defibrillator was implanted. Vagal stimulus–dependent SCA after eating a large bite of food may be the first symptom of BS. For this reason, the electrocardiographic results of the children who had a cardiac arrest after eating a large meal with big bites should be evaluated in detail.
Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in 57%, but patients were highly selected for known and likely Mendelian disorders. The aim of our prospective study was to assess the speed and yield of rapid targeted genomic diagnostics for clinical application.METHODS:
We included 23 critically ill children younger than 12 months in ICUs over a period of 2 years. A quick diagnosis could not be made after routine clinical evaluation and diagnostics. Targeted analysis of 3426 known disease genes was performed by using whole-genome sequencing data. We measured diagnostic yield, turnaround times, and clinical consequences.RESULTS:
A genetic diagnosis was obtained in 7 patients (30%), with a median turnaround time of 12 days (ranging from 5 to 23 days). We identified compound heterozygous mutations in the EPG5 gene (Vici syndrome), the RMND1 gene (combined oxidative phosphorylation deficiency-11), and the EIF2B5 gene (vanishing white matter), and homozygous mutations in the KLHL41 gene (nemaline myopathy), the GFER gene (progressive mitochondrial myopathy), and the GLB1 gene (GM1-gangliosidosis). In addition, a 1p36.33p36.32 microdeletion was detected in a child with cardiomyopathy.CONCLUSIONS:
Rapid targeted genomics combined with copy number variant detection adds important value in the neonatal and pediatric intensive care setting. It led to a fast diagnosis in 30% of critically ill children for whom the routine clinical workup was unsuccessful.
To evaluate the ability to sustain and further reduce central line–associated bloodstream infection (CLABSI) rates in NICUs participating in a multicenter CLABSI reduction collaborative and to assess the impact of the sterile tubing change (TC) technique as an important component in CLABSI reduction.METHODS:
A multi-institutional quality improvement collaborative lowered CLABSI rates in level IV NICUs over a 12-month period. During the 19-month sustain phase, centers were encouraged to monitor and report compliance measures but were only required to report the primary outcome measure of the CLABSI rate. Four participating centers adopted the sterile TC technique during the sustain phase as part of a local Plan-Do-Study-Act cycle.RESULTS:
The average aggregate baseline NICU CLABSI rate of 1.076 CLABSIs per 1000 line days was sustained for 19 months across 17 level IV NICUs from January 2013 to July 2014. Four centers transitioning from the clean to the sterile TC technique during the sustain phase had a 64% decrease in CLABSI rates from the baseline (1.59 CLABSIs per 1000 line days to 0.57 CLABSIs per 1000 line days).CONCLUSIONS:
Sustaining low CLABSI rates in a multicenter collaborative is feasible with team engagement and ongoing collaboration. With these results, we further demonstrate the positive impact of the sterile TC technique in CLABSI reduction efforts.
Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon -induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease.METHODS:
We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined.RESULTS:
Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]).CONCLUSIONS:
Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.
Tattoos, piercing, and scarification are now commonplace among adolescents and young adults. This first clinical report from the American Academy of Pediatrics on voluntary body modification will review the methods used to perform the modifications. Complications resulting from body modification methods, although not common, are discussed to provide the pediatrician with management information. Body modification will be contrasted with nonsuicidal self-injury. When available, information also is presented on societal perceptions of body modification.
To determine if injured children presenting to nondesignated trauma centers are more or less likely to be transferred relative to being admitted based on insurance status.METHODS:
We conducted a cross-sectional study by using the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Pediatric trauma patients receiving care in emergency departments (EDs) at nontrauma centers who were either admitted locally or transferred to another hospital were included. We performed logistic regression analysis adjusting for injury severity and other confounders and incorporated nationally representative weights to determine the association between insurance and transfer or admission.RESULTS:
Nine thousand four hundred and sixty-one ED pediatric trauma events at 386 nontrauma centers met inclusion criteria. EDs that treated a higher proportion of patients with Medicaid had higher odds of transfer relative to admission (odds ratio [OR]: 1.2 per 10% increase in Medicaid; 95% confidence interval [CI]: 1.1–1.4), resulting in overall higher odds of transfer among patients with Medicaid compared with patients with private insurance (OR: 1.3; 95% CI: 1.0–1.5). A patient’s insurance status was not associated with different odds of transfer relative to admission within individual EDs after adjusting for the ED’s proportion of patients with Medicaid (Medicaid OR: 1.0; 95% CI: 0.8–1.1).CONCLUSIONS:
Injured pediatric patients presenting to nondesignated trauma centers are slightly more likely to be transferred than admitted when the ED treats a higher proportion of Medicaid patients. In this study, ongoing concerns about inequities in the delivery of care among hospitals treating high proportions of children with Medicaid are reinforced.
Child mortality remains a global health challenge and has resulted in demand for expanding the global child health (GCH) workforce over the last 3 decades. Institutional partnerships are the cornerstone of sustainable education, research, clinical service, and advocacy for GCH. When successful, partnerships can become self-sustaining and support development of much-needed training programs in resource-constrained settings. Conversely, poorly conceptualized, constructed, or maintained partnerships may inadvertently contribute to the deterioration of health systems. In this comprehensive, literature-based, expert consensus review we present a definition of partnerships for GCH, review their genesis, evolution, and scope, describe participating organizations, and highlight benefits and challenges associated with GCH partnerships. Additionally, we suggest a framework for applying sound ethical and public health principles for GCH that includes 7 guiding principles and 4 core practices along with a structure for evaluating GCH partnerships. Finally, we highlight current knowledge gaps to stimulate further work in these areas. With awareness of the potential benefits and challenges of GCH partnerships, as well as shared dedication to guiding principles and core practices, GCH partnerships hold vast potential to positively impact child health.
Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion).METHODS:
Infants ≥34 weeks’ gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice.RESULTS:
A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38 girls) who were enrolled with SHB were evaluated for auditory toxicity. Of those, 12 infants (13%) had auditory toxicity. On regression analysis controlling for covariates, peak UB (but not peak TSB or peak BAMR), was associated with auditory toxicity (odds ratio 2.41; 95% confidence interval: 1.43–4.07; P = .001). There was significant difference in the area under the receiver operating characteristic curves between UB (0.866), TSB (0.775), and BAMR (0.724) for auditory toxicity (P = .03) after controlling for covariates.CONCLUSIONS:
Unconjugated hyperbilirubinemia indexed by UB (but not TSB or BAMR) is associated with chronic auditory toxicity in infants ≥34 weeks’ GA with SHB.
The increasing incidence of celiac disease (CD) suggests that common infections before the onset of autoimmune diseases could be an important factor in switching the immune response. We aimed to explore the relationship between early clinical events and the development of CD in genetically predisposed infants.METHODS:
In this study, 373 newborns from families with at least 1 relative with CD were recruited, and human leukocyte antigen DQ2- or DQ8-positive infants were followed up with clinical and serological evaluations. Cross tabulation and odds ratios were used to explore the risk associated with single variables, and logistic regression analysis was performed to determine the variables that contributed to the risk of developing CD. Stepwise discriminant analysis was used to determine which variables could distinguish case patients from controls before diagnosis.RESULTS:
The cumulative incidence of CD in this cohort was 6% at 3 years and 13.5% at 5 years of age, and l34 children (14%) developed CD before the sixth year of life. An analysis of adverse events showed a higher frequency of respiratory tract infections among CD patients during the first 24 months of life. In a stepwise discriminant analysis, which included sex and human leukocyte antigen risk class, only respiratory infections in the second and first years of life significantly contributed to discrimination of case patients versus controls.CONCLUSIONS:
A multivariate model of discriminant analysis showed that the frequency of respiratory infections in the first 2 years of life could distinguish children who developed CD from those who did not.
Despite widespread use of the rotavirus vaccine in the last decade, dehydrating illnesses impact almost 2 billion children worldwide annually. Evidence supports oral rehydration therapy as a first-line treatment of mild to moderate dehydration. Ondansetron has proven to be a safe and effective adjunct in children with vomiting. We implemented a clinical pathway in our pediatric emergency department (ED) in January 2005 to improve care for this common condition. Our objective in this study was to determine the long-term impact of the pathway for acute gastroenteritis (AGE) on the proportion of patients receiving intravenous (IV) fluids and ED length of stay (LOS) for discharged patients.METHODS:
Cases were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. We used statistical process control to analyze process and outcome measures for 2 years before and 10 years after pathway implementation.RESULTS:
We included 30 519 patients. We found special cause variation with a downward shift in patients receiving IV fluids after initiation of the pathway and later with addition of ondansetron to the pathway from 48% to 26%. Mean ED LOS for discharged patients with AGE decreased from 247 to 172 minutes. These improvements were sustained over time.CONCLUSIONS:
Implementation of a clinical pathway emphasizing oral rehydration therapy and ondansetron for children with AGE led to decreased IV fluid use and LOS in a pediatric ED. Improvements were sustained over a 10-year period. Our results suggest that quality-improvement interventions for AGE can have long-term impacts on care delivery.
Postpartum depression often remains unaddressed. Screening in well-child care (WCC) may improve early detection, promote maternal recovery, and reduce effects on child development. We assessed the effectiveness of screening for postpartum depression in WCC compared with care as usual (CAU) on outcomes at mother and child levels.METHODS:
In a prospective, quasiexperimental, comparative design, mothers visiting Dutch WCC centers were exposed either to screening at 1, 3, and 6 months postpartum (n = 1843) or to CAU (n = 1246). Assessments were at 3 weeks (baseline), 9 months (the Mini International Neuropsychiatric Interview), and 12 months (the Spielberger State-Trait Anxiety Inventory, the Short-Form 12-Item Health Survey, the Maternal Self-Efficacy in the Nurturing Role questionnaire, and the Ages and Stages Questionnaire–Social Emotional) postpartum.RESULTS:
Significantly fewer mothers in the intervention group were depressed at 9 months postpartum compared with the CAU group (0.6% vs 2.5% for major depression). The adjusted odds ratio was 0.28 (95% confidence interval, 0.12 to 0.63; Cohen’s d, 0.70). For minor and major depression, figures were 3.0% vs 8.4%, and the adjusted odds ratio was 0.40 (95% confidence interval, 0.27 to 0.58; Cohen’s d, 0.51). For parenting, anxiety symptoms, and mental health functioning, the intervention resulted in effect sizes ranging from 0.23 to 0.27. The effect on the child's socioemotional development was negligible.CONCLUSIONS:
Implementation of screening for postpartum depression in WCC should be seriously considered given its positive effects on maternal mental health. The benefits of optimizing the trajectory after screening on maternal and child outcomes need further attention.
In the primary care setting, there are racial and ethnic differences in antibiotic prescribing for acute respiratory tract infections (ARTIs). Viral ARTIs are commonly diagnosed in the pediatric emergency department (PED), in which racial and ethnic differences in antibiotic prescribing have not been previously reported. We sought to investigate whether patient race and ethnicity was associated with differences in antibiotic prescribing for viral ARTIs in the PED.METHODS:
This is a retrospective cohort study of encounters at 7 PEDs in 2013, in which we used electronic health data from the Pediatric Emergency Care Applied Research Network Registry. Multivariable logistic regression was used to examine the association between patient race and ethnicity and antibiotics administered or prescribed among children discharged from the hospital with viral ARTI. Children with bacterial codiagnoses, chronic disease, or who were immunocompromised were excluded. Covariates included age, sex, insurance, triage level, provider type, emergency department type, and emergency department site.RESULTS:
Of 39 445 PED encounters for viral ARTIs that met inclusion criteria, 2.6% (95% confidence interval [CI] 2.4%–2.8%) received antibiotics, including 4.3% of non-Hispanic (NH) white, 1.9% of NH black, 2.6% of Hispanic, and 2.9% of other NH children. In multivariable analyses, NH black (adjusted odds ratio [aOR] 0.44; CI 0.36–0.53), Hispanic (aOR 0.65; CI 0.53–0.81), and other NH (aOR 0.68; CI 0.52–0.87) children remained less likely to receive antibiotics for viral ARTIs.CONCLUSIONS:
Compared with NH white children, NH black and Hispanic children were less likely to receive antibiotics for viral ARTIs in the PED. Future research should seek to understand why racial and ethnic differences in overprescribing exist, including parental expectations, provider perceptions of parental expectations, and implicit provider bias.
Lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth experience significant bullying that undermines their mental and physical health. National health organizations have called for the development of innovative strategies to address LGBTQ bullying. Pediatricians and other clinicians, medical and public health students, interdisciplinary researchers, government officials, school leaders, community members, parents, and youth from around the country came together at a national symposium entitled "LGBTQ Bullying: Translating Research to Action to Improve the Health of All Youth" in May 2016 to generate strategies to prevent LGBTQ bullying and meet the needs of LGBTQ youth experiencing bullying. This article describes key scientific findings on bullying, LGBTQ stigma, and LGBTQ bullying interventions that were shared at the symposium and provides recommendations for pediatricians to address LGBTQ bullying via clinical care, research, interventions, and policy. Symposium participants recommended that pediatricians engage in efforts to foster inclusive and affirming health care environments wherein LGBTQ youth feel comfortable discussing their identities and experiences, identify youth experiencing LGBTQ bullying, and prevent the negative health consequences of bullying among youth. Moreover, pediatricians can attend to how multiple identities (eg, sexual orientation, gender identity, race and/or ethnicity, disability, and others) shape youth experiences of bullying and expand intervention efforts to address LGBTQ bullying in health care settings. Pediatricians can further advocate for evidence-based, antibullying policies prohibiting bullying on the basis of sexual orientation and gender identity. Collaboration between pediatricians and diverse stakeholders can contribute to the development and implementation of lasting change in all forms of bullying, including LGBTQ bullying.