Rehabilitation Outcomes in Children With Acute Flaccid Myelitis From 2014 to 2019: A Multicenter Retrospective Review.

BACKGROUND: Acute flaccid myelitis (AFM) is a childhood illness characterized by sudden-onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who were discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, and neurogenic bowel and bladder in both cohorts. METHODS: Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1, 2014, and October 1, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits. RESULTS: Medical records of 109 children met inclusion criteria; 67 children required inpatient rehabilitation, whereas 42 children were discharged directly home. The median age was 5 years (range 4 months to 17 years), and the median time observed was 417 days (interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (P < 0.001), nutritional support (P < 0.001), and neurogenic bowel (P = 0.004) and bladder (P = 0.002). At follow-up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, P = 0.043); however, the nutritional status and bowel/bladder function were no longer statistically different. CONCLUSIONS: All children made improvements in strength. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow-up; however, recovery of nutritional status and bowel/bladder were similar.

Rehabilitation Care of the Child with an Acute Severe Traumatic Brain Injury.

Children with traumatic brain injury (TBI) represent a unique and evolving population. Recovery and long-term prognosis are variable given the heterogeneity of ages, developmental stages, and types of injuries. This article summarizes important information regarding severe TBI epidemiology, pathophysiology, classification, and acute management. Early and longitudinal involvement of rehabilitation experts, such as pediatric physiatrists, is critical in managing complications and optimizing outcomes.

Botulinum toxin type A outcomes in infants with refractory congenital muscular torticollis.

PURPOSE: The aim of this study was to determine the effectiveness of botulinum toxin type A (BoNT-A) injections in infants with congenital muscular torticollis (CMT) who were refractory to conservative management. METHODS: This was a retrospective study in which all subjects included were seen between 2004 and 2013 and were deemed appropriate for BoNT-A injections. A total of 291 patients were reviewed for inclusion in the study, and 134 patients met the inclusion criteria. Each child was injected with 15-30 units of BoNT-A into each of the following muscles: ipsilateral sternocleidomastoid, upper trapezius, and scalene muscles. The key outcome and variable measurements analyzed included age at time of diagnosis, age at time of initiation of physical therapy, age at time of injection, total number of injection series utilized, muscles injected, and degrees of active and passive cervical rotation and lateral flexion pre- and post-injection. A successful outcome was documented if a child could achieve 45° of active lateral flexion and 80° of active cervical rotation post-injection. Secondary variables including sex, age at time of injection, number of injection series utilized, surgery required, adverse effects of botulinum toxin, presence of plagiocephaly, side of torticollis, orthosis used, presence of hip dysplasia, skeletal anomalies, complications during pregnancy or birth, and any other pertinent information regarding the delivery were also measured. RESULTS: Based on this criteria, 82 children (61%) had successful outcomes. However, only four of the 134 patients required surgical correction. CONCLUSION: BoNT-A may be an effective and safe method for treatment in refractory cases of congenital muscular torticollis.

Remedies for the housewife's nervousness: Life advice in Abraham Myerson's popular self-help texts, 1920-1930.

In 1920, the psychiatrist Abraham Myerson published a self-help book titled The Nervous Housewife. In his book, he argued that the living conditions in urban-industrial America were responsible for a significant increase in the number of housewives who suffered from nervous symptoms. He also warned that women were consequently becoming increasingly discontent with the role and were beginning to desire a life outside motherhood and housewifery. Accordingly, The Nervous Housewife offered housewives and their husbands directions on how to improve her living conditions. This would allow readers to manage and prevent the emergence of nervous symptoms so that women would continue to desire a life as housewife and mother. Throughout the 1920s, Myerson would continue to publish health advice for housewives on how they could manage and eliminate their nervous symptoms. This article analyzes how Myerson connected the everyday experiences and conditions of the housewife's life to her nervousness in his texts and reveals how his motivation was to keep women satisfied with what he deemed was their proper societal role, that of housewife and mother. In doing so, it will also compare his work to other self-help texts on nervousness to illuminate how his how-to guide was innovative, while examining both scholarly and popular reviews of his book to reveal what his peers and readers perceived as the benefits of his advice.

Dosing Variability and Clinical Outcomes of Oxybutynin: A Pediatric Cohort of Patients With Neurogenic Bladder.

Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.

Human papillomavirus vaccination rates in adolescents with cerebral palsy compared to the general population.

PURPOSE: To determine whether adolescents with cerebral palsy (CP) initiate and are up-to-date with the human papillomavirus (HPV) immunization series compared to adolescents in the general population. METHODS: Data on initiation and up-to-date status of the HPV series were collected on adolescents with CP aged 13-17 years old (n = 74) via retrospective medical record review and compared to 616 age-matched peers from the National Immunization Survey, Teen 2019. Analysis by gender, Gross Motor Functional Classification System (GMFCS) level, and ambulatory status was performed in the CP group. RESULTS: Adolescents with CP were three times less likely to start (p < 0.001) and two times less likely to be up-to-date (p = 0.004) with the HPV immunization series compared to age-matched peers. When the HPV immunization series was initiated in adolescents with CP, these adolescents were as likely to complete the series (p = 0.400), with 83.3% being up-to-date. In those with CP, there was no statistical difference in status of the HPV immunization series when comparing gender, GMFCS level, or ambulatory status. CONCLUSION: Adolescents with CP were less likely to start the HPV immunization series; however, they were as likely to be up-to-date with the series if it was initiated. This presents an opportunity for pediatric physiatrists to help reduce the disparity.

Prescribing Patterns of Amantadine During Pediatric Inpatient Rehabilitation After Traumatic Brain Injury: A Multicentered Retrospective Review From the Pediatric Brain Injury Consortium.

OBJECTIVES: To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units. SETTING: Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium. PARTICIPANTS: Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI. DESIGN: Retrospective data revie. MAIN OUTCOME MEASURES: Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects. RESULTS: Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d. CONCLUSION: During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.

A consensus statement on the use of botulinum toxin in pediatric patients.

Botulinum toxin has been used in medicine for the past 30 years. However, there continues to be controversy about the appropriate uses and dosing, especially in the pediatric population. A panel of nine pediatric physiatrists from different regions and previous training programs in the United States were nominated based on institutional reputation and botulinum toxin (BoNT) experience. Based on a review of the current literature, the goal was to provide the rationale for recommendations on the administration of BoNT in the pediatric population. The goal was not only to review safety, dosing, and injection techniques but also to develop a consensus on the appropriate uses in the pediatric population. In addition to upper and lower limb spasticity, the consensus also provides recommendations for congenital muscular torticollis, cervical dystonia, sialorrhea, and brachial plexus palsies.

Determining the impact of a clinic coordinator on patient access and clinic efficiency in a pediatric multidisciplinary spina bifida clinic using medical informatics.

PURPOSE: The objective of this study was to analyze the effects on patient access by decreasing missed appointments after hiring a clinic coordinator using medical informatics. METHODS: A single-center retrospective analysis of the rates of missed appointments before and after hiring a clinic coordinator in a multidisciplinary spinal differences clinic were analyzed using a commercially available business software system (SAP® Business Objects). The total number of clinic visits was collected for each month to determine the access available for patients. RESULTS: The median number of missed appointments per clinic by month before employing the clinic coordinator was higher than in the two years following implementation (p < 0.0005). No differences were seen in the number of available appointment slots per month indicating no new clinics were needed to improve patient access (p = 0.551). Projected billing amounts prior to hiring the clinic coordinator indicated that $91,520 was lost in the 2 years prior to hiring this coordinator compared to $30,160 lost during the 2 years following the creation of this position (p = 0.0009). CONCLUSION: Hiring a clinic coordinator decreased the rate of missed appointments and was a cost-efficient intervention to improve patient access and provide effective patient care in a multidisciplinary setting.

Quantifying Sexual Constitution: Abraham Myerson's Endocrine Study of Male Homosexuality, 1938-1942.

Using the new medical science of endocrinology, scientific sex researchers in the 1920s and 1930s began studying sex hormone excretion as a means to search for the biological basis of human sexuality. One of these researchers was Abraham Myerson, a leading psychiatrist and researcher from Boston who conducted a series of innovative endocrine experiments between 1938 and 1942 in an effort to establish a relationship between sex hormone excretion patterns and homosexuality in men. While prevailing cultural models of heteronormativity identified male homosexuality as an abnormal case of biological femininity in men, Myerson's framework and experimental research transcended this limiting duality of sexual biology. Adopting the theory of bisexuality, he argued that all men possessed a natural variability of masculine and feminine traits in their biological, social, and sexual characteristics, and that the disparity among these traits could be quantified and understood using sex hormones. In reconstructing Myerson's research methods and data analysis, this paper uncovers how he established a distinctive diagnostic method and classification system for male homosexuality and illuminates how he conceptualized and categorized male sexuality as quantifiable and independent of personality.

Cognitive Recovery During Inpatient Rehabilitation Following Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

OBJECTIVES: To characterize the demographics, clinical course, and predictors of cognitive recovery among children and young adults receiving inpatient rehabilitation following pediatric traumatic brain injury (TBI). DESIGN: Retrospective observational, multicenter study. SETTING: Eight acute pediatric inpatient rehabilitation facilities in the United States with specialized programs for treating patients with TBI. PARTICIPANTS: Children and young adults (0-21 years) with TBI (n = 234) receiving inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission and discharge status assessed by the WeeFIM Cognitive Developmental Functional Quotient (DFQ) and Cognitive and Linguistic Scale (CALS). RESULTS: Patients admitted to pediatric inpatient rehabilitation are diverse in cognitive functioning. While the majority of patients make improvements, cognitive recovery is constrained for those admitted with the most severe cognitive impairments. Age, time since injury to rehabilitation admission, and admission WeeFIM Cognitive DFQ are significant predictors of cognitive functioning at discharge from inpatient rehabilitation. CONCLUSIONS: This work establishes a multicenter Pediatric Brain Injury Consortium and characterized the demographics and clinical course of cognitive recovery during inpatient rehabilitation of pediatric patients with TBI to aid in prospective study design.

A risk-stratified approach toward safely resuming OnabotulinumtoxinA injections based on dosing and ambulatory status in pediatric patients with cerebral palsy during the Coronavirus pandemic of 2019 (COVID-19).

PURPOSE: After the onset of the Coronavirus pandemic of 2019-2020 (COVID-19), physicians who inject OnabotulinumtoxinA (BoNT-A) were left with determining risks and benefits in pediatric patients with cerebral palsy. Many of these patients have pre-existing conditions that make them more prone to COVID-19 symptoms, and this susceptibility potentially increases after BoNT-A injections. METHODS: A retrospective chart review of 500 patients identified 256 pediatric patients with cerebral palsy who received an intramuscular BoNT-A injection to determine relative doses used for each Gross Motor Functional Classification Score (GMFCS). Data regarding age, weight, GMFCS, BoNT-A total body dosage, and inpatient hospitalizations for 6 months post-injection were collected. Differences between GMFCS levels were analyzed using one-way analysis of variance testing. Inpatient hospitalizations were recorded and assessed using relative risk to determine the population risk of hospitalization in the setting of initiating injections during the COVID-19 pandemic. RESULTS: Based on GMFCS level, patients who were GMFCS I or II received fewer units of BoNT-A medication per kilogram of body weight compared to GMFCS III-V (p< 0.0005, F= 25.38). There was no statistically significant difference in frequency or time to hospitalization when comparing patients receiving BoNT-A compared to a control group. CONCLUSIONS: Resumption of BoNT-A injections during the time of COVID-19 requires a systematic approach based on risks and potential benefits. Data from this analysis does not show increased risk for patients who received injections historically; however, recommendations for resumption of injections has not previously been proposed in the setting of a pandemic. In this manuscript, a tiered approach to considerations for injections was proposed. Botulinum toxin type A injections have a history of improving spasticity in the pediatric patient with cerebral palsy. Ensuring appropriate selection of patients for injection with BoNT-A during this pandemic is increasingly important.

Simultaneous Quantitation of S(+)- and R(-)-Baclofen and Its Metabolite in Human Plasma and Cerebrospinal Fluid using LC-APCI-MS/MS: An Application for Clinical Studies.

Baclofen is a racemic mixture that is commonly used for the treatment for spasticity. However, the optimal dose and dosing interval to achieve effective cerebral spinal fluid (CSF) concentrations of baclofen are not known. Moreover, it is unclear if there are differences in the ability of R- or S-baclofen to cross the blood-brain barrier and achieve effective CSF concentrations. We have validated a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method with improved selectivity and sensitivity for the simultaneous quantitation of R- and S-baclofen and metabolites in plasma and CSF. Protein precipitation by acetonitrile was utilized to obtain an acceptable recovery of the analytes. The detection and separation of analytes was achieved on a 48 °C-heated Crownpak CR(+) column (150 mm × 4.0 mm, 5µ) with elution using 0.4% formic acid (FA) in water and 0.4% FA in acetonitrile as the mobile phase running at a flow rate of 1.0 mL/min. Accurate quantitation was assured by using this MS/MS method with atmospheric pressure chemical ionization in multiple reaction monitoring (MRM) mode. Therefore, this method is enantioselective, accurate, precise, sensitive, reliable, and linear from 1 to 1500 ng/mL for baclofen and 2 to 4000 ng/mL for the metabolites. An additional method was developed to separate racemic baclofen 3-(4-chlorophenyl)-4 hydroxybutyric acid metabolites for individual concentration determination. Both validated methods were successfully applied to a clinical pharmacokinetic human plasma and CSF study evaluating the disposition of baclofen and metabolites.

Variability of Steady State Oral Baclofen Prescribing Practices in Pediatric Patients With Cerebral Palsy.

The aim of the study was to identify oral baclofen dosing variability at steady state based on weight and Gross Motor Function Classification System level using a retrospective cross-sectional study design. The medical records of 500 pediatric aged patients (age 1-21 yrs) were reviewed to obtain 144 pediatric patients who met inclusion criteria. One-way analysis of variance tests revealed increasing mean doses in baclofen (in milligram per kilogram) with higher Gross Motor Function Classification System levels (P = 0.001). Post hoc Tukey analysis showed patients with higher ambulatory ability (Gross Motor Function Classification System I-II) received a lower total daily dosage than did patients with less ambulatory ability (Gross Motor Function Classification System III-V). A moderate correlation was observed with increasing oral baclofen dose as weight increased (r = 0.43, P < 0.0001). Because of the variability in dosing between Gross Motor Function Classification System levels, prescribing oral baclofen for pediatric patients with cerebral palsy may not follow the traditional model of weight-based dosing seen in other pediatric conditions.

Examining the role of precision medicine with oral baclofen in pediatric patients with cerebral palsy.

PURPOSE OF REVIEW: a)Despite its widespread use, oral baclofen requires a critical review of the pharmacology to determine potential precision medicine applications to improve medication administration. Discussing the dose→exposure→response relationship of oral baclofen allows a conceptual framework in which designing clinical trials would become more successful. This paper seeks to examine some of the areas where variability in exposures can exist lead to undesired clinical responses. RECENT FINDINGS: b)Several factors are at play to implement precision medicine with oral baclofen in the pediatric patient with cerebral palsy. Variations in intestinal absorption, oral baclofen clearance, pharmacogenomic variants, and distribution of this medication into the cerebrospinal fluid cause differences in the amount of baclofen available at the GABA-B receptor site to cause a clinical response. SUMMARY: c)Oral baclofen has significant variability in disposition and clinical response. Research to determine the causes for this variability and controlling for these factors would allow improvement in clinical outcomes.

Considerations for Implementing Precision Therapeutics for Children.

Improving the utilization of pharmacologic agents in the pediatric population yields significant, perhaps life-long, benefits. Genetic factors related to the disposition of a medication or an alteration at the target receptor site contributes to the observed variability of exposure and response between individuals. An additional source of this variability specific to the pediatric population is ontogeny, where age-specific changes during development may require dose adjustments to obtain the same levels of drug exposure and response. With significant improvements in characterizing both the ontogeny and genetic contributions of drug metabolizing enzymes, the time is right to begin placing more emphasis on response rather than only the dose-exposure relationship. The amount of drug target receptors and the relative affinity for binding at that target site may require different levels of systemic exposure to achieve a desired response. Concentration-controlled studies can identify the needed exposure for a response at the drug target, the level of expression of the target site in an individual patient, and the tools required to individualize response. Although pediatrics represents a large spectrum of growth and development, developing tools to improve drug delivery for each individual patient across the spectrum of the ages treated by clinicians remains valuable.

Synthesis of Surface-Analogue Square-Planar Tetranuclear Nickel Hydride Clusters and Bonding to µ4-NR, -O and -BH Ligands.

Tetranuclear Ni complexes were synthesized with bonding to BH, NR, and O in atypical surface-like geometries. The previously reported electron-deficient cluster [( iPr3P)Ni]5H6 (1) reacts with N-methylmorpholine oxide to give [( iPr3P)Ni]4H4(µ4-O) (2), which contains O coordinated in the center of a square-plane arrangement of Ni atoms. Reaction of 1 with benzonitrile gave the square-planar tetranuclear Ni cluster [( iPr3P)Ni]4H4(µ4-NCH2Ph) (3), which contains an imido donor in a square-based-pyramidal geometry. This reaction also gives [( iPr3P)Ni(N≡CPh)]3 (4), with bridging benzonitrile ligands. Trimer 4 was independently synthesized from the reaction of Ni(COD)2, iPr3P, and PhC≡N. The addition of dihydrogen to a 1:1 mixture of [( iPr3P)2Ni]2(N2) and ( iPr3P)2NiCl2 yielded [( iPr3P)Ni]4(µ3-H)4(µ2-Cl)2 (5), with a tetrahedral Ni core, in contrast to the square-planar geometries of 2 and 3. The solid-state structure of 5 was determined using both X-ray and neutron diffraction. Reaction of 5 with LiBH4 gave [( iPr3P)Ni]4H4(µ4-BH)2] (6) via loss of LiCl and H2.

Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy.

BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses. SETTING: Multicenter study based in academic pediatric cerebral palsy clinics. PARTICIPANTS: A total of 49 patients with cerebral palsy who had participated in an oral baclofen pharmacokinetic/pharmacodynamic study. METHODS OR INTERVENTIONS: Of 53 participants in a pharmacokinetic/pharmacodynamic trial, 49 underwent genetic analysis of 307 key genes and 4535 single-nucleotide polymorphisms involved in drug absorption, distribution, metabolism, and excretion. Associations between genotypes and phenotypes of baclofen disposition (weight-corrected and allometrically scaled clearance) and clinical endpoints (improvement from baseline in mean hamstring Modified Tardieu Scale scores from baseline for improvement of R1 spastic catch) were determined by univariate analysis with correction for multiple testing by false discovery rate. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were the genotypic and phenotypic variability of oral baclofen in allometrically scaled clearance and change in the Modified Tardieu Scale angle compared to baseline. RESULTS: After univariate analysis of the data, the SNP of ABCC9 (rs11046232, heterozygous AT versus the reference TT genotype) was associated with a 2-fold increase in oral baclofen clearance (mean 0.51 ± standard deviation 0.05 L/h/kg for the AT genotype versus 0.25 ± 0.07 L/h/kg for the TT genotype, adjusted P < .001). Clinical responses were associated with decreased spasticity by Modified Tardieu Scale in allelic variants with SNPs ABCC12, SLC28A1, and PPARD. CONCLUSIONS: Genetic variation in ABCC9 affecting oral baclofen clearance highlights the need for continued studies of genetic polymorphisms to better characterize variable drug response in children with cerebral palsy. Single-nucleotide polymorphisms in ABCC12, SLC28A1, and PPARD were associated with varied responses, which warrants further investigation to determine their effect on spasticity. LEVEL OF EVIDENCE: II.