Joe DiMaggio Children's Hospital

Abstract Rationale The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively. Conclusions In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

In three infants awaiting orthotopic cardiac transplantation, transplantation was successfully performed with the use of organs from donors who had died from cardiocirculatory causes. The three recipients had blood group O and were in the highest-risk waiting-list category. The mean age of donors was 3.7 days, and the mean time to death after withdrawal from life support was 18.3 minutes. The 6-month survival rate was 100% for the 3 transplant recipients and 84% for 17 control infants who received transplants procured through standard organ donation. The mean number of rejection episodes among the three infants during the first 6 months after surgery was 0.3 per patient, as compared with 0.4 per patient among the controls. Echocardiographic measures of ventricular size and function at 6 months were similar among the three infants and the controls (left ventricular shortening fraction, 43.6% and 44.9%, respectively; P=0.73). No late deaths (within 3.5 years) have occurred in the three infants, and they have had functional and immunologic outcomes similar to those of controls. Mortality while awaiting a transplant is an order of magnitude higher in infants than in adults, and donors who died from cardiocirculatory causes offer an opportunity to decrease this waiting-list mortality.

Reanalysis of Clinical Exome Data and Diagnostic Yield As knowledge about genetic causes of disease improves, periodic reanalysis of clinical exome sequence could yield new genetic information. Thi...

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A

In Brief Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 ± 2.5 yr and 53 ± 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 μg · kg−1 · h−1 (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consump-tion (1.02 ± 0.41 mg · kg−1 · d−1 versus 1.28 ± 0.61 mg · kg−1 · d−1), pain scores at rest (4 ± 2 versus 3 ± 2), and pain scores with coughing (6 ± 2 versus 6 ± 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 μg · kg−1 · h−1) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion. IMPLICATIONS: In children and adolescents, a small dose naloxone infusion (0.25 μg · kg−1 · h−1) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe postoperative pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1β and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

Gain-of-function mutations of Na(V)1.7 have been shown to produce two distinct disorders: Na(V)1.7 mutations that enhance activation produce inherited erythromelalgia (IEM), characterized by burning pain in the extremities; Na(V)1.7 mutations that impair inactivation produce a different, nonoverlapping syndrome, paroxysmal extreme pain disorder (PEPD), characterized by rectal, periocular, and perimandibular pain. Here we report a novel Na(V)1.7 mutation associated with a mixed clinical phenotype with characteristics of IEM and PEPD, with an alanine 1632 substitution by glutamate (A1632E) in domain IV S4-S5 linker. Patch-clamp analysis shows that A1632E produces changes in channel function seen in both IEM and PEPD mutations: A1632E hyperpolarizes (-7 mV) the voltage dependence of activation, slows deactivation, and enhances ramp responses, as observed in Na(V)1.7 mutations that produce IEM. A1632E depolarizes (+17mV) the voltage dependence of fast inactivation, slows fast inactivation, and prevents full inactivation, resulting in persistent inward currents similar to PEPD mutations. Using current clamp, we show that A1632E renders dorsal root ganglion (DRG) and trigeminal ganglion neurons hyperexcitable. These results demonstrate a Na(V)1.7 mutant with biophysical characteristics common to PEPD (impaired fast inactivation) and IEM (hyperpolarized activation, slow deactivation, and enhanced ramp currents) associated with a clinical phenotype with characteristics of both IEM and PEPD and show that this mutation renders DRG and trigeminal ganglion neurons hyperexcitable. These observations indicate that IEM and PEPD mutants are part of a physiological continuum that can produce a continuum of clinical phenotypes.

Multiple endocrine neoplasia type 1 (MEN 1) is associated with parathyroid, enteropancreatic, pituitary, and other tumors. The MEN1 gene, a tumor suppressor, is located on chromosome 11. Affected individuals inherit a mutated MEN1 allele, and tumorigenesis in specific tissues follows inactivation of the remaining MEN1 allele. MEN 1-associated endocrine tumors usually become clinically evident in late adolescence or young adulthood, as high levels of PTH, gastrin, or PRL. Because each of these tumors can usually be controlled with medications and/or surgery, MEN 1 has been regarded mainly as a treatable endocrinopathy of adults. Unlike in MEN 2, early testing of children in MEN 1 families is not recommended. We report a 2.3-cm pituitary macroadenoma in a 5-yr-old boy with familial MEN 1. He presented with growth acceleration, acromegaloid features, and hyperprolactinemia. We tested systematically to see whether his pituitary tumor had causes similar to or different from a typical MEN 1 tumor. Germ line DNA of the propositus and his affected relatives revealed a heterozygous point mutation in the MEN1 gene, which leads to a His139Asp (H139D) amino acid substitution. The patient had no other detectable germ-line mutations on either MEN1 allele. DNA sequencing and fluorescent in situ hybridization with a MEN1 genomic DNA sequence probe each demonstrated one copy of the MEN1 gene to be deleted in the pituitary tumor and not in normal DNA, proving MEN1 "second hit" as a tumor cause. Gsalpha mutation, common in nonhereditary GH-producing tumors, was not detected in this tumor. We conclude that this pituitary macroadenoma showed molecular genetic features of a typical MEN 1-associated tumor. This patient represents the earliest presentation of any morbid endocrine tumor in MEN 1. A better understanding of early onset MEN 1 disease is needed to formulate recommendations for early MEN 1 genetic testing.

Neurocognitive functioning may be compromised in children with type 1 diabetes mellitus (T1DM). The factor most consistently implicated in the long-term neurocognitive functioning of children with T1DM is age of onset. The pediatric literature suggests that glycemic extremes may have an effect on the neurocognitive functioning of children, but findings are mixed. The purpose of this study was to compare the neurocognitive functioning of young children with T1DM diagnosed before 6 yr of age and healthy children (i.e., without chronic illness). Additionally, in the children with T1DM, we examined the relationship between their neurocognitive functioning and glycemic control. Sixty-eight (36 with T1DM and 32 without chronic illness) preschool-age children (M age = 4.4 yr ) were recruited and administered a battery of instruments to measure cognitive, language, and fine motor skills. Children with T1DM performed similar to the healthy controls and both groups' skills fell in the average range. Among children with diabetes, poor glycemic control [higher hemoglobin A1c (HbA1c)] was related to lower general cognitive abilities (r = -0.44,p < 0.04), slower fine motor speed (r = -0.64,p < 0.02), and lower receptive language scores (r = -0.39,p < 0.04). Such findings indicate that young children with T1DM already demonstrate some negative neurocognitive effects in association with chronic hyperglycemia.

An ideal material for repair of congenitally malformed hearts would encourage tissue regeneration with growth potential. Decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) promotes tissue regeneration in animal models and noncardiac human applications. This retrospective review evaluates SIS-ECM for reconstruction of congenital heart defects. From June 2007 to May 2009, SIS-ECM patches were used in 43 operations on 40 patients aged 2 days to 13 years. In 16 cases, the SIS-ECM was used for pericardial closure. The SIS-ECM was used for cardiac or great vessel repair in 37 cases: atrial septal defect repair in 11, pulmonary arterioplasty in 10, right ventricular outflow tract patch in 6, pulmonary monocusp valve creation in 5, superior vena cava patch in 2 and aortoplasty in 2, valve leaflet augmentation in 2, and repair of unroofed coronary sinus in 1. Follow-up was complete. There were 5 deaths, all unrelated to the SIS-ECM. Mean follow-up was 7.85 months (0.5-24 months). No pericardial effusions or intracardiac or intravascular thromboses occurred related to the SIS-ECM. The patches did not shrink or calcify. Four of 5 monocusp valves were competent and none were stenotic. One patient who underwent tricuspid valve anterior leaflet augmentation with SIS-ECM required tricuspid valve replacement 4 months later for severe regurgitation following a catheter-based procedure. Explanted tissue showed resorption of the SIS-ECM, replacement with organized collagen, and re-endothelialization. Repair of congenital heart defects using SIS-ECM is feasible and safe. In valve reconstruction, this procedure shows potential for replacement by autologous tissue. Longer-term follow-up is required to assess the potential for growth.

Genomic imbalance is a major cause of developmental disorders. Microarray-based comparative genomic hybridization (aCGH) has revealed frequent imbalances associated with clinical syndromes, but also a large number of copy number variations (CNVs), which have complicated the interpretation of results. We studied 100 consecutive patients with unexplained mental retardation and a normal karyotype using several platforms of CGH arrays. A genomewide array with 44,290 oligonucleotide probes (OaCGH44K) detected imbalances in 15% of cases studied with sizes ranged from 459 kb to 19 Mb while revealing a small number of CNVs (0.72/individual). Another platform with approximately 240,000 oligonucleotide probes (OaCGH244K) revealed a large number of CNVs (20/individual) in selected cases and their normal parents. We used a comprehensive approach for interpreting the results of aCGH, including consideration of the size, inheritance and gene content of CNVs, and consultation with an online Database of Genomic Variants (DGV) and Online Mendelian Inheritance in Men (OMIM) for information on the genes involved. Our study suggests that genomewide oligonucleotide arrays such as the OaCGH44K platform can be used as a powerful diagnostic tool for detection of genomic imbalances associated with unexplained mental retardation or syndromic autism spectrum disorders. It is interesting to note that a small number of common variants were revealed by OaCGH244K in some study subjects but not in their parents and that some inherited CNVs had altered breakpoints. Further investigations on these alterations may provide useful information for understanding the mechanism of CNVs.

Intrasubstance anterior cruciate ligament (ACL) injuries in children and adolescents were once considered rare occurrences, with tibial eminence avulsion fractures generally regarded as the pediatric ACL injury equivalent. However, with increased single-sport focus, less free play, and year-round training at younger ages, intrasubstance ACL injuries in children and adolescents are being diagnosed with increased frequency. As in the adult, a knee devoid of ligamentous stability predisposes the pediatric patient to meniscal and chondral injuries and early degenerative changes. Management of ACL injuries in skeletally immature patients includes physeal-sparing, partial transphyseal, and complete transphyseal ACL reconstruction. Complications include iatrogenic growth disturbance resulting from physeal violation.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Developmental dysplasia of the hip refers to a continuum of abnormalities in the immature hip that can range from subtle dysplasia to dislocation. The identification of risk factors, including breech presentation and family history, should heighten a physician's suspicion of developmental dysplasia of the hip. Diagnosis is made by physical examination. Palpable hip instability, unequal leg lengths, and asymmetric thigh skinfolds may be present in newborns with a hip dislocation, whereas gait abnormalities and limited hip abduction are more common in older children. The role of ultrasonography is controversial, but it generally is used to confirm diagnosis and assess hip development once treatment is initiated. Bracing is first-line treatment in children younger than six months. Surgery is an option for children in whom nonoperative treatment has failed and in children diagnosed after six months of age. It is important to diagnose developmental dysplasia of the hip early to improve treatment results and to decrease the risk of complications.

Polymyositis (PM) and dermatomyositis (DM) are different disease subtypes of idiopathic inflammatory myopathies (IIMs). The main clinical features of PM and DM include progressive symmetric, predominantly proximal muscle weakness. Laboratory findings include elevated creatine kinase (CK), autoantibodies in serum, and inflammatory infiltrates in muscle biopsy. Dermatomyositis can also involve a characteristic skin rash. Both polymyositis and dermatomyositis can present with extramuscular involvement. The causative factor is agnogenic activation of immune system, leading to immunologic attacks on muscle fibers and endomysial capillaries. The treatment of choice is immunosuppression. PM and DM can be distinguished from other IIMs and myopathies by thorough history, physical examinations and laboratory evaluation and adherence to specific and up-to-date diagnosis criteria and classification standards. Treatment is based on correct diagnosis of these conditions.

To the editor: Somatic, gain-of-function mutations in STAT3 and STAT5 have been described in leukemias and lymphomas[1][1][⇓][2][⇓][3][⇓][4][⇓][5]-[6][6] and, more recently, in CD3-CD4+ T cells from a patient with lymphocytic variant hypereosinophilic syndrome[7][7]; whereas germ line gain-

IMPORTANCE: The present study is the largest on the use and effect of intracranial pressure (ICP) monitoring in pediatric trauma patients. OBJECTIVE: To determine the effect of ICP monitoring on survival in pediatric patients with severe head injuries using the National Trauma Data Bank. DESIGN, SETTING, AND PARTICIPANTS: The National Trauma Data Bank was queried (version 6.2, 2001-2006) for information on patients younger than 17 years admitted to an intensive care unit with blunt traumatic brain injury (TBI), Injury Severity Score (ISS) greater than 9, and Glasgow Coma Scale (GCS) score less than 9. Patients with incomplete medical records and those with intensive care unit length of stay of less than 24 hours were excluded from the study. MAIN OUTCOMES AND MEASURES: Parametric comparisons (t tests and χ2 as appropriate) were performed to compare patients who received ICP monitoring with those who did not. Stepwise logistic regression methods were used to assess whether ICP monitoring in the presence of other variables (age, sex, ISS, Revised Trauma Score, and GCS score) was associated with survival. RESULTS: Monitoring of ICP was performed in only 7.7% of patients who met the monitoring criteria recommended by the Brain Trauma Foundation. There were no significant differences in age, sex, or GCS score. After adjustment for admission GCS score, age group, sex, Revised Trauma Score, and injury ISS, ICP monitoring was associated with a reduction in mortality only for patients with a GCS score of 3 (odds ratio, 0.64; 95% CI, 0.43-1.00). Comparison between the 2 groups showed that the ICP monitoring group had a longer hospital length of stay (21.0 days vs 10.4 days; P < .001), longer intensive care unit stay (12.6 vs 6.3 days; P < .001), and more ventilator days (9.2 vs 4.7; P < .001). CONCLUSIONS AND RELEVANCE: Despite current Brain Trauma Foundation guidelines, ICP monitoring is used infrequently in the pediatric population. The data suggest that there is a small, yet statistically significant, survival advantage in patients who have ICP monitors and a GCS score of 3. However, all patients with ICP monitors experienced longer hospital length of stay, longer intensive care unit stay, and more ventilator days compared with those without ICP monitors. A prospective observational study would be helpful to accurately define the population for whom ICP monitoring is advantageous.

OBJECTIVE: Family-centered care has become integral to the provision of quality neonatal intensive care. However, practices that reflect the core principles of family-centered care have not been described fully in the literature or implemented and evaluated consistently within newborn intensive care. The objective of this study was to create a family-centered care map that enhances the ability of the health care team to work with families to coordinate and deliver care in a holistic manner to meet the developmental, physical, and psychosocial needs of NICU patients and their families. METHODS: Potentially better practices were developed for sequential clinical phases by using standardized methods. These included focus groups with families, brainstorming sessions with staff, literature review, and input from established family advisory groups and family-centered care experts. Potentially better practices then were integrated into the family-centered care map that was configured in a Web-based format. Overall utility will be evaluated by determining the effect of the family-centered care map on length of stay, parental satisfaction, and family-centered care beliefs and practices among NICU staff. RESULTS: Sixty-three potentially better practices were identified for 7 clinical phases and 3 variations that were believed to characterize the clinical course of a typical NICU patient. A prototype of the Web-based family-centered care map that illustrates the clinical phases with links to the related potentially better practices, operational processes, and case studies was created. Baseline data from a care provider survey, from a family satisfaction survey, and on length of stay have been collected. CONCLUSIONS: Quality improvement methods and collaboration among 3 centers led to the development of an innovative Web-based resource to assist individual care providers and family advisors to provide comprehensive family-centered care to infants and families. Implementation of the family-centered care map has potential to affect positively the quality of newborn intensive care and lead to improved long-term outcomes.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.