Brain Magnetic Resonance Imaging in Congenital Cytomegalovirus With Failed Newborn Hearing Screen.

BACKGROUND: In 2013, Utah enacted legislation requiring that infants failing newborn hearing screening be tested for cytomegalovirus infection. As a result, cytomegalovirus-infected infants are being identified because of hearing deficits. The neuroimaging findings in this population have not been characterized. METHODS: Retrospective medical record review was used to identify patients seen at the University of Utah and Primary Children's Hospitals in Salt Lake City, Utah, who failed newborn hearing screening. A cohort of patients with congenital cytomegalovirus infection, brain magnetic resonance imaging (MRI), and sedated auditory brainstem response testing was studied. RESULTS: Seventeen patients were identified; 11 (65%) were female. Confirmatory auditory brainstem response testing, performed at a median age 29 days, showed profound hearing loss in 8 (47%) subjects, severe loss in two (12%), moderate loss in two (12%), and mild loss in three (18%); two (12%) subjects had normal hearing. The diagnosis of cytomegalovirus infection was made at a median age 23 days. Brain imaging was performed at a median age 65 days. Ten (59%) subjects had one or more neuroimaging abnormality. White matter lesions were found in eight (47%) subjects, cysts in three (18%), and stroke in two (12%). Polymicrogyria was identified in two (12%) subjects. Seven (41%) subjects had normal brain MRIs. CONCLUSIONS: These results indicate that most infants whose cytomegalovirus infections were identified after failing newborn hearing screening had abnormal brain MRIs. Our results suggest that brain MRIs should be considered in infants with congenital cytomegalovirus infections who are identified through hearing screening programs.

Pediatric Career Choice: Insights From a Novel, Medical School Pathway Program.

OBJECTIVE: Research on how medical students choose a career in pediatrics is either dated or conflated with primary care career choice. Capitalizing on student participation in an innovative, time-variable, competency based pathway program, Education in Pediatrics Across the Continuum (EPAC), the authors explored the process of career decision-making in students at 5 medical schools (including 4 EPAC sites) who begin medical school with an interest in pediatrics. METHODS: Individual, semistructured interviews were conducted with students in 5 groups: Group 1: accepted into EPAC, n = 8; Group 2: accepted into EPAC, opted-out, n = 4; Group 3 applied to EPAC, not accepted, pursued pediatrics, n = 4; Group 4: applied to EPAC, not accepted, did not pursue pediatrics, n = 3; Group 5: pursued pediatrics at a non-EPAC site, n = 6. Data collection and analysis occurred iteratively, with inductive coding of data revealing patterns in data explored in subsequent interviews and refined in the final analysis. RESULTS: All students described intrinsic guiding principles, that is, "doing what you love," that attracted them to pediatrics. They described extrinsic, phase-specific experiences before medical school, before clerkship, and in clerkship that shaped their perceptions of a career in pediatrics and shed light on collective values of different specialties. Student's assessment of how their guiding principles aligned with the collective values of pediatrics, which students encountered in the clerkship phase, was a key to making career decisions. CONCLUSIONS: Intrinsic and extrinsic factors do not act alone but interact in clerkships, and influence career choice of students who enter medical school with an interest in pediatrics.

Congenital and perinatal infections.

Congenital and perinatal infections represent major causes of permanent disability among children worldwide. Linked together by the acronym TORCH, denoting Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus, congenital infections can result from only a modest number of human pathogens that cross the placenta and infect the fetus. Although congenital rubella syndrome has been eliminated in the Americas by immunization, several pathogens discussed in this chapter cannot currently be prevented by vaccines or effectively treated with the available antimicrobial drugs. Due to the immaturity of the immune system, newborn infants are at risk for postnatally acquired infections with certain viruses and several bacteria. This chapter summarizes the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of selected pathogens that can damage the developing nervous system. As emphasized by the persisting challenges of preventing congenital cytomegalovirus infection and the emergence of severe brain damage associated with congenital Zika syndrome, these pathogens remain important causes of cerebral palsy, epilepsy, and intellectual disability.

Expanding the genetic and clinical spectrum of the NONO-associated X-linked intellectual disability syndrome.

The NONO gene encodes a nuclear protein involved in RNA metabolism. Hemizygous loss-of-function NONO variants have been associated with syndromic intellectual disability and with left ventricular noncompaction (LVNC). A two-year-old boy presented to the University of Utah's Penelope Undiagnosed Disease Program with developmental delay, nonfamilial features, relative macrocephaly, and dilated cardiomyopathy with LVNC and Ebstein anomaly. Brain MRI showed a thick corpus callosum, mild Chiari I malformation, and a flattened pituitary. Exome sequencing identified a novel intronic deletion (c.154+5_154+6delGT) in the NONO gene. Splicing studies demonstrated intron 4 read-through and the use of an alternative donor causing the frameshift p.Asn52Serfs*6. Family segregation analysis showed that the variant occurred de novo in the boy's unaffected mother. MRI and endocrine findings suggest that hypopituitarism may contribute to growth failure, abnormal thyroid hormone levels, cryptorchidism, or delayed puberty in patients with NONO-associated disease. Also, including this case LVNC has been observed in five out of eight patients, and this report also confirms an association between loss of NONO and Ebstein anomaly. In some cases, unrelated individuals share the same pathogenic NONO variants but do not all have clinically significant LVNC, suggesting that additional modifiers may contribute to cardiac phenotypes.

Intracranial Calcifications in Young Children.

Intracranial calcifications in young infants, while suggesting intrauterine infections, can also be due to numerous other conditions, including rare genetic disorders. We describe 2 children in whom the presence and pattern of intracranial calcifications led to the diagnosis of uncommon genetic disorders, Adams-Oliver syndrome and Aicardi-Goutieres syndrome. Differentiating genetic conditions from intrauterine infections or other causes of intracranial calcifications enables practitioners to provide accurate counseling regarding prognosis and recurrence risk.

Education in Pediatrics Across the Continuum (EPAC): First Steps Toward Realizing the Dream of Competency-Based Education.

The Education in Pediatrics Across the Continuum (EPAC) Study Group is developing the first competency-based, time-variable progression from undergraduate medical education (UME) to graduate medical education (GME) in the history of medical education in the United States. EPAC, an innovation project sponsored by the Association of American Medical Colleges and supported by the Josiah Macy Jr. Foundation, was developed through a collaboration between five medical schools and multiple professional organizations with an interest in undergraduate and graduate medical education. The planning and implementation process demanded cooperatively addressing practical barriers such as education requirements for licensure and developing approaches to learner assessment that provided meaningful information about competency. Each participating school now has at least three cohorts of learners participating, and the program is transitioning its first cohort of students from UME to GME based on achievement of predetermined competencies that allow this transition. Members of the first cohort of learners in this program have begun their pediatric residency training at different times beginning in late 2016, confirming the feasibility of competency-based advancement from UME to GME in pediatrics. Although there is still much to learn about the outcomes of EPAC learners' professional development in residency training and beyond, EPAC has defined an operational approach to a different path through medical school and into residency training, based on the attainment of competence.

Families as Partners in Hospital Error and Adverse Event Surveillance.

Importance: Medical errors and adverse events (AEs) are common among hospitalized children. While clinician reports are the foundation of operational hospital safety surveillance and a key component of multifaceted research surveillance, patient and family reports are not routinely gathered. We hypothesized that a novel family-reporting mechanism would improve incident detection. Objective: To compare error and AE rates (1) gathered systematically with vs without family reporting, (2) reported by families vs clinicians, and (3) reported by families vs hospital incident reports. Design, Setting, and Participants: We conducted a prospective cohort study including the parents/caregivers of 989 hospitalized patients 17 years and younger (total 3902 patient-days) and their clinicians from December 2014 to July 2015 in 4 US pediatric centers. Clinician abstractors identified potential errors and AEs by reviewing medical records, hospital incident reports, and clinician reports as well as weekly and discharge Family Safety Interviews (FSIs). Two physicians reviewed and independently categorized all incidents, rating severity and preventability (agreement, 68%-90%; κ, 0.50-0.68). Discordant categorizations were reconciled. Rates were generated using Poisson regression estimated via generalized estimating equations to account for repeated measures on the same patient. Main Outcomes and Measures: Error and AE rates. Results: Overall, 746 parents/caregivers consented for the study. Of these, 717 completed FSIs. Their median (interquartile range) age was 32.5 (26-40) years; 380 (53.0%) were nonwhite, 566 (78.9%) were female, 603 (84.1%) were English speaking, and 380 (53.0%) had attended college. Of 717 parents/caregivers completing FSIs, 185 (25.8%) reported a total of 255 incidents, which were classified as 132 safety concerns (51.8%), 102 nonsafety-related quality concerns (40.0%), and 21 other concerns (8.2%). These included 22 preventable AEs (8.6%), 17 nonharmful medical errors (6.7%), and 11 nonpreventable AEs (4.3%) on the study unit. In total, 179 errors and 113 AEs were identified from all sources. Family reports included 8 otherwise unidentified AEs, including 7 preventable AEs. Error rates with family reporting (45.9 per 1000 patient-days) were 1.2-fold (95% CI, 1.1-1.2) higher than rates without family reporting (39.7 per 1000 patient-days). Adverse event rates with family reporting (28.7 per 1000 patient-days) were 1.1-fold (95% CI, 1.0-1.2; P = .006) higher than rates without (26.1 per 1000 patient-days). Families and clinicians reported similar rates of errors (10.0 vs 12.8 per 1000 patient-days; relative rate, 0.8; 95% CI, .5-1.2) and AEs (8.5 vs 6.2 per 1000 patient-days; relative rate, 1.4; 95% CI, 0.8-2.2). Family-reported error rates were 5.0-fold (95% CI, 1.9-13.0) higher and AE rates 2.9-fold (95% CI, 1.2-6.7) higher than hospital incident report rates. Conclusions and Relevance: Families provide unique information about hospital safety and should be included in hospital safety surveillance in order to facilitate better design and assessment of interventions to improve safety.

Child Neurology Recruitment and Training: Views of Residents and Child Neurologists From the 2015 AAP/CNS Workforce Survey.

BACKGROUND: To assess and compare resident and practicing child neurologists' attitudes regarding recruitment and residency training in child neurology. METHODS: A joint task force of the American Academy of Pediatrics and the Child Neurology Society conducted an electronic survey of child neurology residents (n = 305), practicing child neurologists (n = 1290), and neurodevelopmental disabilities specialists (n = 30) in 2015. Descriptive and multivariate analyses were performed. RESULTS: Response rates were 32% for residents (n = 97; 36% male; 65% Caucasian) and 40% for practitioners (n = 523; 63% male; 80% Caucasian; 30% lifetime certification). Regarding recruitment, 70% (n = 372) attributed difficulties recruiting medical students to insufficient early exposure. Although 68% (n = 364) reported that their medical school required a neurology clerkship, just 28% (n = 152) reported a child neurology component. Regarding residency curriculum, respondents supported increased training emphasis for genetics, neurodevelopmental disabilities, and multiple other subspecialty areas. Major changes in board certification requirements were supported, with 73% (n = 363) favoring reduced adult neurology training (strongest predictors: fewer years since medical school P = 0.003; and among practicing child neurologists, working more half-day clinics per week P = 0.005). Furthermore, 58% (n = 289) favored an option to reduce total training to 4 years, with 1 year of general pediatrics. Eighty-two percent (n = 448) would definitely or probably choose child neurology again. CONCLUSIONS: These findings provide support for recruitment efforts emphasizing early exposure of medical students to child neurology. Increased subspecialty exposure and an option for major changes in board certification requirements are favored by a significant number of respondents.

Outcome and Cost of Inpatient Hospitalization for Intravenous Dihydroergotamine Treatment of Refractory Pediatric Headache.

BACKGROUND: To determine the cost and efficacy of admitting patients for intravenous dihydroergotamine treatment and to identify factors associated with a higher likelihood of response to treatment. METHODS: We performed a retrospective review of all pediatric hospitalizations from 2001 to 2010 for intravenous dihydroergotamine therapy for headache. Data were collected using the REDcap database and consisted of multiple variables, including preadmission demographics, headache duration, use of prophylactic medications, inpatient therapies including dihydroergotamine dosing, procedures, consultations, total hospital cost, and headache severity at discharge and at follow-up. RESULTS: Seventy-four percent of the 145 individuals who were hospitalized were female. Mean age was 14.9 years. Headache was described as chronic or daily in almost all patients and 28 (19%) had status migrainosus. Sixty-six percent had a first-degree relative with migraine. The average length of stay was 3.7 days, and the average cost was $7569 per hospitalization. Patients received an average of eight doses of dihydroergotamine. At the time of discharge, 63% of patients reported improvement. Follow-up information was available for 68% of the cohort at a median of 42 days after discharge, and 21 of 99 patients (21%) experienced sustained relief of headache. Response to dihydroergotamine was correlated with a lower rate of comorbid diagnoses, lumbar puncture, and outpatient neuroimaging. Response also correlated to less expensive hospitalizations with an average cost of $5379 per hospitalization versus $7105 per hospitalization without positive response. Response was also correlated with a patient receiving more doses of intravenous dihydroergotamine. CONCLUSIONS: Although intravenous dihydroergotamine is an effective abortive medication for intractable migraine, it may provide only short-term headache relief in many pediatric patients. Hospitalization is relatively costly with only modest long-term benefit, especially in patients with chronic migraine or chronic daily headache.

The child neurology clinical workforce in 2015: Report of the AAP/CNS Joint Taskforce.

OBJECTIVES: More than a decade has passed since the last major workforce survey of child neurologists in the United States; thus, a reassessment of the child neurology workforce is needed, along with an inaugural assessment of a new related field, neurodevelopmental disabilities. METHODS: The American Academy of Pediatrics and the Child Neurology Society conducted an electronic survey in 2015 of child neurologists and neurodevelopmental disabilities specialists. RESULTS: The majority of respondents participate in maintenance of certification, practice in academic medical centers, and offer subspecialty care. EEG reading and epilepsy care are common subspecialty practice areas, although many child neurologists have not had formal training in this field. In keeping with broader trends, medical school debts are substantially higher than in the past and will often take many years to pay off. Although a broad majority would choose these fields again, there are widespread dissatisfactions with compensation and benefits given the length of training and the complexity of care provided, and frustrations with mounting regulatory and administrative stresses that interfere with clinical practice. CONCLUSIONS: Although not unique to child neurology and neurodevelopmental disabilities, such issues may present barriers for the recruitment of trainees into these fields. Creative approaches to enhance the recruitment of the next generation of child neurologists and neurodevelopmental disabilities specialists will benefit society, especially in light of all the exciting new treatments under development for an array of chronic childhood neurologic disorders.

Recognition and Management of Acute Flaccid Myelitis in Children.

BACKGROUND: In 2014-2015, several regions of the United States experienced an outbreak of acute flaccid myelitis in pediatric patients. A common, unique feature was disease localization to the gray matter of the spinal cord. METHODS: We report 11 children, ages 13 months to 14 years (median 9 years), in the Intermountain West who presented with extremity weakness (n = 10) or cranial neuropathy (n = 1) of varying severity without an apparent etiology. RESULTS: All children experienced acute paralysis, and 10 had symptoms or signs that localized to the spinal cord. Maximum paralysis occurred within 4 days of onset in all patients. All had spinal gray matter lesions consistent with acute myelitis detected by magnetic resonance imaging; no single infectious cause was identified. Despite therapy with intravenous immunoglobulin, corticosteroids, or plasma exchange, nine of 10 (90%) children had motor deficits at follow-up. CONCLUSIONS: Recognition of this disorder enables clinicians to obtain appropriate imaging and laboratory testing, initiate treatment, and provide families with accurate prognostic information. In contrast to other causes of acute flaccid paralysis in childhood, most children with acute flaccid myelitis have residual neurological deficits.

Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention.

Virus encephalitis remains a major cause of acute neurological dysfunction and permanent disability among children worldwide. Although some disorders, such as measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella-zoster virus-associated neurological conditions, have largely disappeared in resource-rich regions because of widespread immunization programs, other disorders, such as herpes simplex virus encephalitis, West Nile virus-associated neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous system, cannot be prevented. Moreover, emerging viral disorders pose new, potential threats to the child's nervous system. This review summarizes current information regarding the epidemiology of virus encephalitis, the diagnostic methods available to detect central nervous system infection and identify viral pathogens, and the available treatments. The review also describes immune-mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D-aspartate receptor antibody encephalitis, conditions that mimic virus encephalitis and account for a substantial proportion of childhood encephalitis.

Variation in printed handoff documents: Results and recommendations from a multicenter needs assessment.

BACKGROUND: Handoffs of patient care are a leading root cause of medical errors. Standardized techniques exist to minimize miscommunications during verbal handoffs, but studies to guide standardization of printed handoff documents are lacking. OBJECTIVE: To determine whether variability exists in the content of printed handoff documents and to identify key data elements that should be uniformly included in these documents. SETTING: Pediatric hospitalist services at 9 institutions in the United States and Canada. METHODS: Sample handoff documents from each institution were reviewed, and structured group interviews were conducted to understand each institution's priorities for written handoffs. An expert panel reviewed all handoff documents and structured group-interview findings, and subsequently made consensus-based recommendations for data elements that were either essential or recommended, including best overall printed handoff practices. RESULTS: Nine sites completed structured group interviews and submitted data. We identified substantial variation in both the structure and content of printed handoff documents. Only 4 of 23 possible data elements (17%) were uniformly present in all sites' handoff documents. The expert panel recommended the following as essential for all printed handoffs: assessment of illness severity, patient summary, action items, situation awareness and contingency plans, allergies, medications, age, weight, date of admission, and patient and hospital service identifiers. Code status and several other elements were also recommended. CONCLUSIONS: Wide variation exists in the content of printed handoff documents. Standardizing printed handoff documents has the potential to decrease omissions of key data during patient care transitions, which may decrease the risk of downstream medical errors.

Changes in medical errors after implementation of a handoff program.

BACKGROUND: Miscommunications are a leading cause of serious medical errors. Data from multicenter studies assessing programs designed to improve handoff of information about patient care are lacking. METHODS: We conducted a prospective intervention study of a resident handoff-improvement program in nine hospitals, measuring rates of medical errors, preventable adverse events, and miscommunications, as well as resident workflow. The intervention included a mnemonic to standardize oral and written handoffs, handoff and communication training, a faculty development and observation program, and a sustainability campaign. Error rates were measured through active surveillance. Handoffs were assessed by means of evaluation of printed handoff documents and audio recordings. Workflow was assessed through time-motion observations. The primary outcome had two components: medical errors and preventable adverse events. RESULTS: In 10,740 patient admissions, the medical-error rate decreased by 23% from the preintervention period to the postintervention period (24.5 vs. 18.8 per 100 admissions, P<0.001), and the rate of preventable adverse events decreased by 30% (4.7 vs. 3.3 events per 100 admissions, P<0.001). The rate of nonpreventable adverse events did not change significantly (3.0 and 2.8 events per 100 admissions, P=0.79). Site-level analyses showed significant error reductions at six of nine sites. Across sites, significant increases were observed in the inclusion of all prespecified key elements in written documents and oral communication during handoff (nine written and five oral elements; P<0.001 for all 14 comparisons). There were no significant changes from the preintervention period to the postintervention period in the duration of oral handoffs (2.4 and 2.5 minutes per patient, respectively; P=0.55) or in resident workflow, including patient-family contact and computer time. CONCLUSIONS: Implementation of the handoff program was associated with reductions in medical errors and in preventable adverse events and with improvements in communication, without a negative effect on workflow. (Funded by the Office of the Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services, and others.).

A diagnostic paradigm including cytomegalovirus testing for idiopathic pediatric sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: To determine the feasibility and cost effectiveness of incorporating cytomegalovirus (CMV) testing to determine the etiology of pediatric hearing loss. STUDY DESIGN: Retrospective study of children presenting with sensorineural hearing loss (SNHL) at one institution from 2008 to 2013. METHODS: Children aged 3 years or younger who presented to the senior author (A.P.) between May 2008 and September 2013 with confirmed SNHL were evaluated. These children underwent a sequential diagnostic paradigm that incorporated CMV testing if no obvious etiology could be determined from the history or physical examination. RESULTS: One hundred eleven children with SNHL were evaluated between 2008 and 2013. Eighty-three children underwent CMV testing, imaging, and a genetic evaluation. Those with confirmed or probable CMV-induced SNHL made up 30% of all children tested (n = 25), the largest group identified. CMV screening had the lowest cost compared to genetic testing or imaging for all types of hearing loss, except for those with auditory neuropathy spectrum disorder. CONCLUSION: We present the first sequential diagnostic paradigm utilizing CMV testing for children presenting with SNHL. The relatively high incidence of CMV-induced SNHL, the low cost for this assay, and the indirect benefits from early diagnosis support the role of early CMV testing for these patients. LEVEL OF EVIDENCE: 4.