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.

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.).

Factors associated with intern noncompliance with the 2003 Accreditation Council for Graduate Medical Education's 30-hour duty period requirement.

BACKGROUND: In 2003 the Accreditation Council for Graduate Medical Education mandated work hour restrictions. Violations can results in a residency program being cited or placed on probation. Recurrent violations could results in loss of accreditation. We wanted to determine specific intern and workload factors associated with violation of a specific mandate, the 30-hour duty period requirement. METHODS: Retrospective review of interns' performance against the 30-hour duty period requirement during inpatient ward rotations at a pediatric residency program between June 24, 2008 and June 23, 2009. The analytical plan included both univariate and multivariable logistic regression analyses. RESULTS: Twenty of the 26 (77%) interns had 80 self-reported episodes of continuous work hours greater than 30 hours. In multivariable analysis, noncompliance was inversely associated with the number of prior inpatient rotations (odds ratio: 0.49, 95% confidence interval (0.38, 0.64) per rotation) but directly associated with the total number of patients (odds ratio: 1.30 (1.10, 1.53) per additional patient). The number of admissions on-call, number of admissions after midnight and number of discharges post-call were not significantly associated with noncompliance. The level of noncompliance also varied significantly between interns after accounting for intern experience and workload factors. Subject to limitations in statistical power, we were unable to identify specific intern characteristics, such as demographic variables or examination scores, which account for the variation in noncompliance between interns. CONCLUSIONS: Both intern and workload factors were associated with pediatric intern noncompliance with the 30-hour duty period requirement during inpatient ward rotations. Residency programs must develop information systems to understand the individual and experience factors associated with noncompliance and implement appropriate interventions to ensure compliance with the duty hour regulations.

Patent foramen ovale in children with migraine headaches.

OBJECTIVE: To determine the prevalence of patent foramen ovale (PFO) in children with migraine. STUDY DESIGN: Children aged 6.0 to 18.0 years with migraine headache were evaluated for PFO and right-to-left shunting with color-flow Doppler scanning, saline solution contrast transthoracic echocardiography, and contrast transcranial Doppler scanning. RESULTS: The population consisted of 109 children with migraine; 38 (35%) with aura and 71 (65%) without aura. The overall PFO prevalence was 35%, similar to the general population (35% vs 25%; P = .13). However, compared with the general population (25%), the PFO prevalence was significantly greater in subjects with aura (50%, P = .0004) but similar in those without aura (27%, P = .73). Atrial shunt size was not associated with the presence or absence of aura. CONCLUSION: Children with migraine with aura have a significantly higher prevalence of PFO compared with those without aura or the general population. These data suggest that PFO may contribute to the pathogenesis of migraine with aura in children and have implications for clinical decision making.

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.

The Child Neurology Workforce Study: pediatrician access and satisfaction.

OBJECTIVE: To assess the opinions of pediatricians regarding the supply and utilization of child neurologists in the United States. STUDY DESIGN: A 32-item questionnaire was circulated by e-mail to a random sample of 5000 pediatricians with the assistance of the American Academy of Pediatrics. RESULTS: After 2 mailings, 422 responses were received. Respondents ranged in age from 30 to 75 years (median 50 years), 60.4% were male, 96% were board certified in pediatrics, and 76% had a 2 or more-week rotation in child neurology during pediatric training. Approximately 79% indicated that there were few or too few child neurologists in their area, and 90% indicated that there were few or too few child neurologists in the United States. Sixty-one percent indicated that they always or almost always seek consultation from a child neurologist for a child with new onset seizures; 7% and 21% seek consultations for children with migraine or tics. The delay for child neurology consultation was 5 or more weeks in 63% and >12 weeks in 15%. Satisfaction with child neurologists was linked to the level of inter-physician communication. Neither satisfaction nor wait time influenced the frequency of consultations. Increasing level of patient complexity and parental expectations were cited as reasons for increasing numbers of consultations with child neurologists. CONCLUSIONS: Pediatricians perceive that a work force shortage exists in child neurology. Satisfaction with child neurology consultations is linked to communication with pediatricians.

Congenital cytomegalovirus infection: progressive postnatal chorioretinitis.

Immunocompetent children with congenital cytomegalovirus rarely have postnatal progression of chorioretinitis. Optimal treatment of this disease is not well established. The authors describe an infant who had congenital cytomegalovirus infection with postnatal progression of chorioretinitis and required an extended course of ganciclovir therapy.

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.

Neglected zoonotic diseases in Nigeria: role of the public health veterinarian.

Zoonotic diseases accounts for about 75% of emerging infectious disease and can be devastating to both human and animal health globally. A subset of zoonotic diseases is referred to as "neglected zoonotic diseases - NZDs" as they mainly affect poor populations who live in close proximity to domestic or wild animals often in areas where access to health and adequate sanitary facilities are not available. Furthermore, underestimation of the burden of NZD has continually led to its further neglect in least developed countries such as Nigeria. Controlling zoonotic infections including NZDs in animals is crucial in reducing human infections. Veterinarians provides an understanding of the epidemiology of infectious diseases in animal population and are therefore integral for the overall reduction in global burden of NZDs worldwide. Due to the current lack of and in some cases weak involvement of Veterinarians in policy issues related to zoonotic diseases, there is need to elucidate their importance in NZDs control in Nigeria. This review therefore summarises the neglected zoonotic diseases so far documented in Nigeria and also highlight the important role of the Veterinarian in their prevention and control within both human and animal population. Important recommendations to strengthen the role of the public health Veterinarian for sustainable control of NZDs were made.

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.

Rheumatic chorea: relationship to systemic manifestations and response to corticosteroids.

OBJECTIVE: To describe Sydenham chorea among children in a cohort of patients with rheumatic fever (RF). STUDY DESIGN: An existing database was used to identify demographic characteristics, clinical manifestations, and therapy in persons with RF identified in Salt Lake City, Utah, from 1985 through January 2002. RESULTS: Of 584 cases in the database, 537 (91%) were new-onset RF (median age of 10 years) and 177 (33%) had chorea. Patients with chorea were more often female (OR = 0.37, 95% CI = 0.25-0.55, P < .0001) and were less likely to have carditis or arthritis. Prednisone treatment may lead to a shortened course of chorea (4.0 weeks in prednisone-treated [n = 32] vs 9.0 weeks in untreated [n = 14]; P < .0001). Among 33 patients seen at a median of 10.3 years (range 6.3-14.9 years) after their initial bout of chorea, 20% reported residual tremor or mood swings. Ten of the 33 (30%) had one or more recurrences of chorea. CONCLUSIONS: Chorea affected one-third of the children with RF. Patients with chorea were less likely to have severe cardiac or rheumatologic complications of RF. Therapy with prednisone shortened the duration of rheumatic chorea; some reported recurrences of chorea and had minor neurologic sequelae.

Intra-arterial thrombolysis in a 2-year-old with cardioembolic stroke.

Recombinant tissue plasminogen activator, although the standard of care for the management of acute ischemic stroke in adults, is used infrequently in children. The authors describe the use of intra-arterial recombinant tissue plasminogen activator in a young child with embolic stroke. Thrombolysis restored flow to the affected middle cerebral artery and appeared to limit the extent of the infarction and the severity of the subsequent neurologic deficits.

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.

Shift Schedules and Intern Work Hours, Patient Numbers, Conference Attendance, and Sleep at a Single Pediatric Residency Program.

OBJECTIVE: The effects of 2011 Accreditation Council on Graduate Medical Education (ACGME) duty hour standards on intern work hours, patient load, conference attendance, and sleep have not been fully determined. We prospectively compared intern work hours, patient numbers, conference attendance, sleep duration, pattern, and quality in a 2011 ACGME duty hour-compliant shift schedule with a 2003 ACGME duty hour-compliant call schedule at a single pediatric residency program. METHODS: Interns were assigned to shift or call schedules during 4 alternate months in the winter of 2010-2011. Work hours, patient numbers, conference attendance, sleep duration, pattern, and quality were tracked. RESULTS: Interns worked significantly fewer hours per week on day (73.2 hours) or night (71.6 hours) shifts than during q4 call (79.6 hours; P < .01). During high census months, shift schedule interns cared for significantly more patients/day (8.1/day shift vs 6.2/call; P < .001) and attended significantly fewer conferences than call schedule interns. Night shift interns slept more hours per 24-hour period than call schedule interns (7.2 ± 0.5 vs 6.3 ± 0.9 hours; P < .05) and had more consistent sleep patterns. CONCLUSIONS: A shift schedule resulted in reduced intern work hours and improved sleep duration and pattern. Although intern didactic conference attendance declined significantly during high census months, opportunities for experiential learning remained robust with unchanged or increased intern patient numbers.

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.