Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams.

OBJECTIVES: To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. STUDY DESIGN: Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age. RESULTS: Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). CONCLUSIONS: Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01525316.

Pediatric liver transplantation in Latin America: Where do we stand?

LT started in LA in 1968, and pediatric LT records are available starting in the 1990s. Currently, eight countries perform pediatric LT in LA. Registries by national organizations fail to report robust data on pediatric LT. The aim of this paper was to report on the pediatric LT activity in LA. Data were gathered retrospectively through information available in the national registries websites and from local centers. Of the eight countries that report pediatric LT activity, Brazil, Argentina, Mexico, and Colombia have adequate registries of the numbers of LT performed. These countries concentrate most of the activity for pediatric LT. A total of 4593 pediatric LT were reported in LA. Websites for national organizations do not provide open data on post-transplant survival rates or waiting list mortality. The information herein is based on reports by local centers. Overall, survival from select centers is similar to that reported on North American and European registries, between 80 and 90% in the first year post-transplant. In conclusion, pediatric LT activity is growing in LA, especially in Brazil and Argentina. However, the lack of an appropriate LA registry restricts the assessment of quality and therefore restricts interventions aimed at quality improvements in different regions.

Challenges in the diagnosis and management of neonatal sepsis.

Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.

Lactoferrin for prevention of neonatal sepsis.

Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6,000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF's role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide.

Worldwide Survey on Approach to Thrombolysis in Acute Ischemic Stroke With Large Vessel Occlusion.

Background and Objectives: With recent trials suggesting that endovascular thrombectomy (EVT) alone may be noninferior to combined intravenous thrombolysis (IVT) with alteplase and EVT and that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke, we sought to understand current practices around the world for treating acute ischemic stroke with large vessel occlusion (LVO) depending on the center of practice (IVT-capable vs IVT and EVT-capable stroke center). Methods: The electronic survey launched by the Practice Current section of Neurology: Clinical Practice included 6 clinical and 8 demographic questions. A single-case scenario was presented of a 65-year-old man presenting with right hemiplegia with aphasia with a duration of 1 hour. Imaging showed left M1-MCA occlusion with no early ischemic changes. The respondents were asked about their treatment approach in 2 settings: the patient presented to (1) the IVT-only capable center and (2) the IVT and EVT-capable center. They were also asked about the thrombolytic agent of choice in current and ideal circumstances for these settings. Results: A total of 203 physicians (42.9% vascular neurologists) from 44 countries completed the survey. Most participants (55.2%) spent ≥50% of their time delivering stroke care. The survey results showed that in current practice, more than 90% of respondents would offer IVT + EVT to patients with LVO stroke presenting to either an EVT-capable (91.1%) or IVT-only-capable center (93.6%). Although nearly 80% currently use alteplase for thrombolysis, around 60% would ideally like to switch to tenecteplase independent of the practice setting. These results were similar between stroke and non-stroke neurologists. Discussion: Most physicians prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion independent of the practice setting.

Emerging Subspecialties: Pediatric Movement Disorders Neurology.

Pediatric movement disorders (PMD) neurologists care for infants, children, and adolescents with conditions that disrupt typical movement; serving as important subspecialist child neurologists in both academic and private practice settings. In contrast to adult movement disorders neurologists whose "bread and butter" is hypokinetic Parkinson disease, PMD subspecialty practice is often dominated by hyperkinetic movement disorders including tics, dystonia, chorea, tremor, and myoclonus. PMD neurology practice intersects with a variety of subspecialties, including neonatology, developmental pediatrics, rehabilitation medicine, epilepsy, child & adolescent psychiatry, psychology, orthopedics, genetics & metabolism, and neurosurgery. Over the past several decades, significant advancements in the PMD field have included operationalizing definitions for distinct movement disorders, recognizing the spectrum of clinical phenotypes, expanding research on genetic and neuroimmunologic causes of movement disorders, and advancing available treatments. Subspecialty training in PMD provides trainees with advanced clinical, diagnostic, procedural, and management skills that reflect the complexities of contemporary practice. The child neurologist who is fascinated by the intricacies of child motor development, appreciates the power of observation skills coupled with a thoughtful physical examination, and is excited by the challenge of the unknown may be well-suited to a career as a PMD specialist.

Parasite antigen in serum predicts the presence of viable brain parasites in patients with apparently calcified cysticercosis only.

BACKGROUND: Computed tomography (CT) remains the standard neuroimaging screening exam for neurocysticercosis, and residual brain calcifications are the commonest finding. Magnetic resonance imaging (MRI) is more sensitive than CT but is rarely available in endemic regions. Enzyme-linked immunoelectrotransfer blot (EITB) assay uses antibody detection for diagnosis confirmation; by contrast, enzyme-linked immunosorbent assay (ELISA) antigen detection (Ag-ELISA) detects circulating parasite antigen. This study evaluated whether these assays predict undetected viable cysts in patients with only calcified lesions on brain CT. METHODS: Serum samples from 39 patients with calcified neurocysticercosis and no viable parasites on CT were processed by Ag-ELISA and EITB. MRI was performed for each patient within 2 months of serologic testing. Conservatively high ELISA and EITB cutoffs were used to predict the finding of viable brain cysts on MRI. RESULTS: Using receiver operating characteristic-optimized cutoffs, 7 patients were Ag-ELISA positive, and 8 had strong antibody reactions on EITB. MRI showed viable brain cysts in 7 (18.0%) patients. Patients with positive Ag-ELISA were more likely to have viable cysts than Ag-ELISA negatives (6/7 vs 1/32; odds ratio, 186 [95% confidence interval, 1-34 470.0], P < .001; sensitivity 85.7%, specificity 96.9%, positive likelihood ratio of 27 to detect viable cysts). Similar but weaker associations were also found between a strong antibody reaction on EITB and undetected viable brain cysts. CONCLUSIONS: Antigen detection, and in a lesser degree strong antibody reactions, can predict viable neurocysticercosis. Serological diagnostic methods could identify viable lesions missed by CT in patients with apparently only calcified cysticercosis and could be considered for diagnosis workup and further therapy.

Surgical treatment of movement disorders in neurometabolic conditions.

Refractory movement disorders are a common feature of inborn errors of metabolism (IEMs), significantly impacting quality of life and potentially leading to life-threatening complications such as status dystonicus. Surgical techniques, including deep brain stimulation (DBS) and lesioning techniques, represent an additional treatment option. However, the application and benefits of these procedures in neurometabolic conditions is not well understood. This results in challenges selecting surgical candidates and counseling patients preoperatively. In this review, we explore the literature of surgical techniques for the treatment of movement disorders in IEMs. Globus pallidus internus DBS has emerged as a beneficial treatment option for dystonia in Panthotate-Kinase-associated Neurodegeneration. Additionally, several patients with Lesch-Nyhan Disease have shown improvement following pallidal stimulation, with more robust effects on self-injurious behavior than dystonia. Although there are numerous reports describing benefits of DBS for movement disorders in other IEMs, the sample sizes have generally been small, limiting meaningful conclusions. Currently, DBS is preferred to lesioning techniques. However, successful use of pallidotomy and thalamotomy in neurometabolic conditions has been reported and may have a role in selected patients. Surgical techniques have also been used successfully in patients with IEMs to treat status dystonicus. Advancing our knowledge of these treatment options could significantly improve the care for patients with neurometabolic conditions.

Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders.

Background: POLR3A pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders. Cases: We describe the range of movement disorders seen in six patients (four female, two male) with POLR3A variants [three novel (c.2214del, c.3775G>A, c.3905G>T) and six previously reported (c.760C>T, c.1771-7C>G, c.1909+22G>A, c.2005C>T, c.2422C>T, c.3337-11T>C)]. Patient 1 presented with a neonatal progeroid syndrome and developed parkinsonism, dystonia, ataxia, and spasticity. Patient 2 presented with infant-onset rapidly progressive chorea, and dystonia. Three patients (patients 3, 5, 6) presented predominantly with ataxia in combination with spasticity and dystonia. Patient 4 developed segmental dystonia during adolescence and ataxia in early adulthood. Four patients had vertical gaze impairment. The most common brain MRI abnormality was T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain. Conclusion: POLR3A-related disorders exhibit significant phenotypic pleomorphism. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.

The Phenomenology of Tics and Tic-Like Behavior in TikTok.

BACKGROUND: Pediatricians and pediatric subspecialists worldwide have reported a marked increase in functional (conversion) disorders with tic-like behaviors during the COVID-19 pandemic. These patients often report frequent viewing of Tourette syndrome (TS) TikTok videos, suggesting disease modeling. We aimed to evaluate tic phenomenology in videos posted on TikTok. METHODS: The 100 most-viewed videos under #tourettes in TikTok were randomly assigned to two of three primary reviewers (<2 years independent practice), all pediatric neurologists specializing in movement disorders, for extraction and classification of tic phenomenology. Initial disagreements were solved by consensus. If not resolved, one of five senior reviewers (>2 years independent pediatric movement disorder practice) served as a tiebreaker. In addition, two primary and one senior reviewer rated each video on a Likert scale from 1 = "All the tics are typical of TS" to 5 = "None of the tics are typical of TS". Median scores and Spearman correlation between primary and senior reviewers were calculated. RESULTS: Six videos without tic-like behaviors were excluded. Most videos depicted coprophenomena (coprolalia: 53.2%; copropraxia: 20.2%), often with unusual characteristics. Frequently, videos demonstrated atypical phenomenology such as very strong influence by the environment (motor: 54.3%; phonic: 54.3%), aggression (19.1%), throwing objects (22.3%), self-injurious behaviors (27.7%), and long phrases (>3 words; 45.7%). Most videos portrayed atypical, nontic behaviors (median [IQR] Likert ratings: 5 [4-5]). Primary vs. senior rater scores demonstrated moderate agreement (r = 0.46; P < 0.001). CONCLUSIONS: TS symptom portrayals on highly viewed TikTok videos are predominantly not representative or typical of TS.

EEG Correlates of Active Stopping and Preparation for Stopping in Chronic Tic Disorder.

Motor inhibition is an important cognitive process involved in tic suppression. As the right frontal lobe contains important inhibitory network nodes, we characterized right superior, middle, and inferior frontal gyral (RSFG, RMFG, RIFG) event-related oscillations during motor inhibition in youth with chronic tic disorders (CTD) versus controls. Fourteen children with CTD and 13 controls (10-17 years old) completed an anticipated-response stop signal task while dense-array electroencephalography was recorded. Between-group differences in spectral power changes (3-50 Hz) were explored after source localization and multiple comparisons correction. Two epochs within the stop signal task were studied: (1) preparatory phase early in the trial before motor execution/inhibition and (2) active inhibition phase after stop signal presentation. Correlation analyses between electrophysiologic data and clinical rating scales for tic, obsessive-compulsive symptoms, and inattention/hyperactivity were performed. There were no behavioral or electrophysiological differences during active stopping. During stop preparation, CTD participants showed greater event-related desynchronization (ERD) in the RSFG (γ-band), RMFG (ß, γ-bands), and RIFG (θ, α, ß, γ-bands). Higher RSFG γ-ERD correlated with lower tic severity (r = 0.66, p = 0.04). Our findings suggest RSFG γ-ERD may represent a mechanism that allows CTD patients to keep tics under control and achieve behavioral performance similar to peers.

Deep Brain Stimulation for Pediatric Dystonia: A Review of the Literature and Suggested Programming Algorithm.

Deep brain stimulation (DBS) is an established intervention for use in pediatric movement disorders, especially dystonia. Although multiple publications have provided guidelines for deep brain stimulation patient selection and programming in adults, there are no evidence-based or consensus statements published for pediatrics. The result is lack of standardized care and underutilization of this effective treatment. To this end, we assembled a focus group of 13 pediatric movement disorder specialists and 1 neurosurgeon experienced in pediatric deep brain stimulation to review recent literature and current practices and propose a standardized approach to candidate selection, implantation target site selection, and programming algorithms. For pediatric dystonia, we provide algorithms for (1) programming for initial session and follow-up sessions, and (2) troubleshooting side effects encountered during programming. We discuss common side effects, how they present, and recommendations for management. This topical review serves as a resource for movement disorders specialists interested in using deep brain stimulation for pediatric dystonia.

Clinical RNA sequencing confirms compound heterozygous intronic variants in RYR1 in a patient with congenital myopathy, respiratory failure, neonatal brain hemorrhage, and d-transposition of the great arteries.

BACKGROUND: Defects in the RYR1 (OMIM#180901) gene lead to Ryanodine receptor type 1-related myopathies (RYR1-RM); the most common subgroup of congenital myopathies. METHODS: Congenital myopathy presents a diagnostic challenge due to the need for multiple testing modalities to identify the many different genetic etiologies. In this case, the patient remained undiagnosed after whole-exome sequencing (WES), chromosomal microarray, methylation analysis, targeted deletion and duplication studies, and targeted repeat expansion studies. Clinical whole-genome sequencing (WGS) was then pursued as part of a research study to identify a diagnosis. RESULTS: WGS identified compound heterozygous RYR1 intronic variants, RNA sequencing confirmed both variants to be pathogenic causing RYR1-RM in a phenotype of severe congenital hypotonia with respiratory failure from birth, neonatal brain hemorrhage, and congenital heart disease involving transposition of the great arteries. CONCLUSION: While there is an ongoing debate about the clinical superiority of WGS versus WES for patients with a suspected genetic condition, this scenario highlights a weakness of WES as well as the added cost and delay in diagnosis timing with having WGS follow WES or even ending further genetic testing with a negative WES. While knowledge gaps still exist for many intronic variants, transcriptome analysis provides a way of validating the resulting dysfunction caused by these variants and thus allowing for appropriate pathogenicity classification. This is the second published case report of a patient with pathogenic intronic variants in RYR1-RM, with clinical RNA testing confirming variant pathogenicity and therefore the diagnosis suggesting that for some patients careful analysis of a patient's genome and transcriptome are required for a complete genetic evaluation. The diagnostic odyssey experienced by this patient highlights the importance of early, rapid WGS.

Post-transplant lymphoproliferative disorders in a cohort of adult patients with a liver transplant from a reference hospital in Bogotá, Colombia / Trastornos linfoproliferativos en una cohorte de pacientes adultos con trasplante hepático atendidos en un hospital de referencia en Bogotá, Colombia.

Introduction: The post-transplant lymphoproliferative disorders (PTLD) are characterized by an uncontrolled pathological lymphoid proliferation as a consequence of transplant immunosuppression therapy. Objective: To characterize the clinical and pathological characteristics of PTLD in a cohort of adult patients with liver transplant during a 15 year period at the Hospital Universitario Fundación Santa Fe de Bogota. Materials and methods: We conducted an observational retrospective study by searching for the PTLD cases diagnosed during the study period in the databases of the Liver Transplantation Unit and the Pathology Department. We collected the epidemiological, clinical, and pathological information and performed the corresponding statistics analyses. Results: During the research period, 572 patients were transplanted; the incidence of PTDL was 2.44%; 79% of them were man and the average age at the time of diagnosis was 62.5 years; 71% of the cases were diagnosed during the first year after the transplant and the same percentage EBV-seropositive patients. The most frequent pathological phenotype was monomorphic and the majority of tumors was detected in the hepatic hilum. The one-year survival was 50%. Conclusion: The high proportion of early cases and the high frequency of Epstein-Barr virus seropositivity both in donors and receptors drewour attention. More studies are necessary to have a better understanding of this condition in Colombia. This is the first PTLD clinical and pathological analysis in liver-transplant patients from Colombia to date.

Introducción. Los trastornos linfoproliferativos después de un trasplante se caracterizan por la proliferación descontrolada de linfocitos como consecuencia del tratamiento inmunosupresor posterior a este. Objetivo. Caracterizar clínica y patológicamente los casos de trastornos linfoproliferativos después de trasplante (Post-Transplant Lymphoproliferative Disorders, PTLD) en una cohorte de pacientes adultos con trasplante de hígado atendidos a lo largo de 15 años en el Hospital Universitario Fundación Santa Fe de Bogotá. Materiales y métodos. Se hizo un estudio observacional retrospectivo a partir de la revisión de las bases de datos de la Unidad de Trasplante Hepático y del Departamento de Patología del Hospital en busca de los casos de PTLD diagnosticados durante el periodo de estudio. Se recolectó la información epidemiológica, clínica y patológica, y se adelantaron los análisis estadísticos. Resultados. Durante el periodo de estudio, hubo 572 pacientes con trasplante de hígado, la incidencia de trastornos linfoproliferativos fue de 2,44 %, el 79 % en hombres, y la edad promedio en el momento del diagnóstico fue de 62,5 años. El 71 % de los casos se presentó durante los primeros 12 meses después del trasplante y el mismo porcentaje fue seropositivo para el virus de Epstein-Barr (EBV). El fenotipo patológico más frecuente fue el monomorfo y la mayoría de los tumores se detectaron en el hilio hepático. La supervivencia al año fue del 50 %. Conclusiones. Llamó la atención el alto porcentaje de casos de presentación temprana, así como la gran frecuencia de seropositividad para el EBV tanto en los donantes como en los receptores. Deben adelantarse estudios más detallados para una mejor comprensión de esta enfermedad en el país. Este es el primer análisis clínico y patológico de PTLD en pacientes con trasplante de hígado adelantado en Colombia hasta la fecha.

Rational adaptation under task and processing constraints: implications for testing theories of cognition and action.

The authors assume that individuals adapt rationally to a utility function given constraints imposed by their cognitive architecture and the local task environment. This assumption underlies a new approach to modeling and understanding cognition-cognitively bounded rational analysis-that sharpens the predictive acuity of general, integrated theories of cognition and action. Such theories provide the necessary computational means to explain the flexible nature of human behavior but in doing so introduce extreme degrees of freedom in accounting for data. The new approach narrows the space of predicted behaviors through analysis of the payoff achieved by alternative strategies, rather than through fitting strategies and theoretical parameters to data. It extends and complements established approaches, including computational cognitive architectures, rational analysis, optimal motor control, bounded rationality, and signal detection theory. The authors illustrate the approach with a reanalysis of an existing account of psychological refractory period (PRP) dual-task performance and the development and analysis of a new theory of ordered dual-task responses. These analyses yield several novel results, including a new understanding of the role of strategic variation in existing accounts of PRP and the first predictive, quantitative account showing how the details of ordered dual-task phenomena emerge from the rational control of a cognitive system subject to the combined constraints of internal variance, motor interference, and a response selection bottleneck.

[Intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru]. / Hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso al nacer en tres hospitales de Lima, Perú.

To describe the frequency and severity of intraventricular hemorrhage and periventricular leukomalacia in low birth-weight neonates in three hospitals in Lima, Peru, 385 newborn babies weighing under 2,000 g at birth were evaluated between May 2012 and July 2014. Brain ultrasounds were obtained at 40 weeks' gestation, 3-5 days of life, and 3-4 weeks of life. Intraventricular hemorrhage occurred in 19.2% of neonates weighing under 1,500 g and was severe (grade III or with periventricular hemorrhagic infarction) in 9.6% of neonates under 1,500 g. Mortality in infants with intraventricular hemorrhage was 47.1%, while periventricular leukomalacia was found in 5.4% of neonates 1,500 g and under; both diagnoses were more frequent in lower-weight babies. The frequency of intraventricular hemorrhage is similar to that reported in other countries; however, severity and mortality are greater.

Con el objetivo de describir la frecuencia y severidad de la hemorragia intraventricular y leucomalacia periventricular en neonatos de bajo peso en tres hospitales de Lima, Perú se evaluaron 385 neonatos menores de 2000 g de peso al nacer durante mayo del 2012 a julio del 2014. Se obtuvo ultrasonidos cerebrales a las 40 semanas de gestación, 3-5 días de vida y 3-4 semanas de vida. Hemorragia intraventricular se presentó en 19,2% neonatos con menos de 1500 g y fue severa (grado III o con infarto hemorrágico periventricular) en 9,6% neonatos menores de 1500 g. La mortalidad en neonatos con hemorragia intraventricular fue de 47,1%, se encontró leucomalacia periventricular en 5,4% de los neonatos menores de 1500 g. Ambos diagnósticos fueron más frecuentes en neonatos con menor peso. La frecuencia de hemorragia intraventricular es similar a lo reportado en otros países; sin embargo, la severidad y mortalidad es mayor.

Antibiotic Overuse in Premature Low Birth Weight Infants in a Developing Country.

BACKGROUND: Neonatal sepsis is a leading cause of child morbidity and mortality, especially in premature and low birth weight infants. Prompt antibiotic therapy is warranted, but its inappropriate use leads to bacterial resistance and adverse outcomes. Our objective is to describe the antibiotic use for late-onset sepsis in Peruvian premature infants. METHODS: This study is a prospective study as a secondary analysis of a clinical trial in 3 neonatal care units in Peru. We included infants in the first 72 hours of life, with birth weight (BW) <2000 g. We described the antibiotic use as length of therapy (LOT) per 1000 patient days (PD) and antibiotic courses. RESULTS: We included 408 neonates, with 12,204 PD of follow-up; 253 infants (62%) had a BW ≤1500 g. Total antibiotic use for late-onset sepsis was 2395 LOT (196 LOT/1000 PD). Two-hundred and seventy-one patients (66.4%) did not receive antibiotics for late-onset sepsis during their hospitalization. In total, 204 antibiotic courses were administered; 92 infants (22.5%) received 1 course, and 45 (11.0%) received 2-5 antibiotic courses. Mean duration of antibiotic course was 10.8 days (standard deviation: ±7.3). We found a significant association between a lower BW and increased antibiotic use per day (P < 0.001). The most commonly used antibiotics were vancomycin (143 LOT/1000 PD), carbapenems (115 LOT/1000 PD), aminoglycosides (72 LOT/1000 PD) and ampicillin (41 LOT/1000 PD). CONCLUSIONS: Premature infants receive antibiotics for longer than recommended periods of time. Antibiotic overuse is greater in neonates with lower BW. Vancomycin is the most used antibiotic. There is an urgent need to develop antimicrobial stewardship programs in our setting.

Combined predictors of neurodevelopment in very low birth weight preterm infants.

OBJECTIVE: To evaluate the combined prognostic value of neurological examination, head circumference and cranial ultrasound for neurodevelopmental delay (NDD) in very low birth weight (VLBW, <1500 g) preterm infants. METHODS: Prospective follow-up study. Preterm infants with VLWB were assessed for NDD using the Mullen Scales of Early Learning test at 24 months of corrected age. Abnormal neurological examination (≥2 deviant items of Hammersmith neurological examination), microcephaly and major ultrasound abnormalities, each performed at term age, were evaluated as predictors of NDD in a multivariable Poisson model. RESULTS: 35/132 infants (26.5%) had NDD. In the multivariable analysis, microcephaly (RR, 3.2; 95% CI, 1.6-6.7) and major ultrasound abnormalities (RR, 2.7; 95% CI, 1.3-5.7) were associated to NDD. The combination of the two tests showed the highest positive predictive value (100%; 95% CI, 51%-100%), while the combination of normal neurological examination, no major US findings and normal head size at term showed the highest negative predictive value (89%; 95% CI, 78%-95%). The maximum under receiver operating characteristic curve area was for microcephaly or major ultrasound abnormalities (AUC 0.74 (0.65-0.83)). CONCLUSION: The combination of head circumference, cranial ultrasound and neurological examination at term age is useful to predict NDD in VLBW preterm infants.

Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation brain mapping.

PURPOSE: We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). METHODS: As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses. RESULTS: Before ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM. Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897). CONCLUSIONS: This study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships.