Social Determinants of Health Are Associated with Failed Bowel Management for Children with Anorectal Malformations.

INTRODUCTION: Children with anorectal malformations (ARMs) benefit from bowel management programs (BMPs) to manage constipation or fecal incontinence. We aimed to understand the role of social determinants of health (SDOH) in outcomes following BMPs in this population. MATERIALS AND METHODS: A single-institution, institutional review board (IRB) approved, retrospective review was performed in children with ARM who underwent BMP from 2014 to 2021. Clinical, surgical, and SDOH data were collected. Children were stratified as clean or not clean per the Rome IV criteria at the completion of BMP. Descriptive statistics were computed. Categorical variables were analyzed via Fisher's exact tests and continuous variables with Mood's median tests. RESULTS: In total, 239 patients who underwent BMP were identified; their median age was 6.62 years (interquartile range [IQR]: 4.78-9.83). Of these, 81 (34%) were not clean after completing BMP. Children with prior history of antegrade enema procedures had a higher rate of failure. Children who held public insurance, lived within driving distance, had unmarried parents, lived with extended family, and lacked formal support systems had a significant association with BMP failure (p < 0.05 for all). Type of ARM, age at repair, type of repair, age at BMP, and type of BMP regimen were not significantly associated with failure. CONCLUSIONS: There is a significant correlation of failure of BMPs with several SDOH elements in patients with ARM. Attention to SDOH may help identify high-risk patients in whom additional care may lead improved outcomes following BMP.

Outcomes of children with constipation and autism spectrum disorder treated with antegrade continence enemas.

BACKGROUND: Treatment of functional constipation (FC) in children with autism spectrum disorder (ASD) is challenging due to sensory and behavioral issues. We aimed to understand whether antegrade continence enemas (ACEs) are successful in the treatment of FC in children with ASD. METHODS: A single-institution retrospective review was performed in children diagnosed with ASD and FC who underwent appendicostomy or cecostomy placement from 2007 to 2019. Descriptive statistics regarding soiling and complications were calculated. RESULTS: There were 33 patients included, with a median age of 9.7 years at the time of ACE initiation. The average intelligence quotient was 63.6 (SD = 18.0, n = 12), the average behavioral adaptive score was 59.9 (SD = 11.1, n = 13), and the average total Child Behavioral Checklist score was 72.5 (SD = 7.1, n = 10). Soiling rates were significantly lower following ACE initiation (42.3% vs. 14.8%, p = 0.04). Behavioral issues only prevented 1 patient (3.0%) from proper ACE use. Eleven patients (36.6%) were able to transition to laxatives. There were significant improvements in patient-reported outcomes measures and quality of life. CONCLUSION: Placement of an appendicostomy or cecostomy for management of FC in children with severe ASD was successful in treating constipation and improving quality of life.

Pilot study of an adult bowel management program for fecal incontinence.

OBJECTIVE: Bowel management programs are efficacious in pediatric patients with fecal incontinence or intractable constipation unresponsive to standard treatment. No studies have been done examining outcomes in adults. The objective of this study was to assess continence and quality of life outcomes in adults who have underwent bowel management program. METHODS: A retrospective review of patients 16 or older at the time they underwent a bowel management program for fecal incontinence or constipation was performed. Data collected included intake and follow-up stool and urinary continence, patient-reported outcomes measures (Cleveland Clinic Constipation Score, Baylor Continence Scale, Vancouver Symptom Score for Dysfunctional Elimination), and an age-adjusted health-related quality of life measure. RESULTS: The cohort included 38 patients with a median age of 19 years (range: 16-55) when they underwent our program. 50% of patients were female and the majority (33, 87%) were White. The most common diagnosis was anorectal malformation (16, 42%) followed by functional constipation (10, 27%). Stool continence rates improved after undergoing the program (52.7% prior to 87.6% at follow-up, p<0.01). There was significant improvement in the Baylor Continence Scale, Cleveland Clinic Constipation Score, and PedsQL (p<0.05). CONCLUSIONS: Adult patients who underwent a bowel management program for severe fecal incontinence or constipation show significant improvement in stool continence rates, patient-reported outcomes measures, and quality of life. A bowel management program (in-person or via telemedicine) is a feasible treatment strategy for adult patients who fail standard management of fecal incontinence or constipation and should be offered when appropriate. LEVEL OF EVIDENCE: III.

Antegrade continence enemas in children with functional constipation and dyssynergic defecation: Go or no go?

OBJECTIVE: To assess outcomes of children with functional constipation after antegrade continence enemas (ACEs) and determine if pre operative anorectal manometry (AMAN) findings, including dyssynergic defecation, are associated with outcomes. METHODS: A retrospective review of pediatric patients with functional constipation who received a Malone appendicostomy or cecostomy after failed medical management was conducted. Patients were included if they had AMAN data prior to their operation. Patients that underwent colonic resection were excluded. Demographics, clinical characteristics, manometry results, and post ACE outcomes were obtained. Descriptive statistics were performed. RESULTS: Thirty-nine patients were identified with median age at ACE of 8.9 years (IQR: 7.2-12.6) and median follow-up of 2.5 years (IQR: 1.8-3.2 years). Twenty patients (51%) were female and most (35, 92%) were White. All patients had severe constipation prior to ACE and 59% had fecal incontinence. Thirty-four patients (87%) received a Malone and 5 (13%) received a cecostomy. Post ACE, 35 (90%) were clean with daily flushes and 6 (15%) eventually successfully transitioned to laxatives only. Awake AMAN and balloon expulsion test were performed in 15 patients, with 14 (93%) displaying evidence of dyssynergic defecation. Twelve of 14 of patients (86%) with dyssynergia were clean with ACE at follow-up. because of the majority of patients being clean post ACE, there was limited power to detect predictors of poor outcomes. CONCLUSIONS: ACEs are successful treatment options for patients with severe constipation and fecal incontinence, including those with dyssynergic defecation. Larger studies are needed to identify factors predictive of poor outcomes. LEVEL OF EVIDENCE: III.

Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial.

BACKGROUND: Valproic acid, a histone deacetylase inhibitor, has beneficial effects in the setting of cancer, neurologic diseases, and traumatic injuries. In animal models of traumatic injury, a single dose of valproic acid has been shown to reduce mortality. The purpose of this trial was to determine the maximum tolerated single dose of intravenous valproic acid in healthy humans. METHODS: A double-blinded, placebo-controlled, dose-escalation trial design was used to identify dose-limiting toxicities in healthy subjects who received a single dose of intravenous valproic acid. Patients were monitored for adverse events and data were collected for pharmacokinetic, pharmacodynamic, and safety profiling of valproic acid. RESULTS: Fifty-nine healthy subjects (mean 30 ± 12 years) were enrolled. Forty-four subjects received valproic acid in doses from 15 to 150 mg/kg. The most common adverse events were hypoacusis (n = 19), chills (n = 18), and headache (n = 16). The maximum tolerated dose was 140 mg/kg. Dose-limiting toxicities included headache and nausea lasting longer than 12 h. No drug-related abnormalities were seen in other safety measures including laboratory tests, hemodynamic parameters, cardiac rhythm monitoring, and cognitive testing. A two-compartment model was predictive of valproic acid concentration-time profiles, with a strong correlation (R 2 = 0.56) observed between the number of reported adverse events and the dose level. CONCLUSIONS: The maximum tolerated dose of intravenous valproic acid in healthy subjects is 140 mg/kg. This is significantly higher than the previously established maximum tolerated dose of 60-75 mg/kg. Next, the safety and tolerability of high-dose valproic acid will be tested in trauma patients in hemorrhagic shock. ClinicalTrials.gov Identifier: NCT01951560.

Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock.

BACKGROUND: Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In a nonsurvival model of TBI + HS, addition of high-dose valproic acid (VPA) (300 mg/kg) to hetastarch reduced brain lesion size and associated swelling 6 hours after injury; whether this would have translated into better neurologic outcomes remains unknown. It is also unclear whether lower doses of VPA would be neuroprotective. We hypothesized that addition of low-dose VPA to normal saline (NS) resuscitation would result in improved long-term neurologic recovery and decreased brain lesion size. METHODS: TBI was created in anesthetized swine (40-43 kg) by controlled cortical impact, and volume-controlled hemorrhage (40% volume) was induced concurrently. After 2 hours of shock, animals were randomized (n = 5 per group) to NS (3× shed blood) or NS + VPA (150 mg/kg). Six hours after resuscitation, packed red blood cells were transfused, and animals were recovered. Peripheral blood mononuclear cells were analyzed for acetylated histone-H3 at lysine-9. A Neurological Severity Score (NSS) was assessed daily for 30 days. Brain magnetic resonance imaging was performed on Days 3 and 10. Cognitive performance was assessed by training animals to retrieve food from color-coded boxes. RESULTS: There was a significant increase in histone acetylation in the NS + VPA-treated animals compared with NS treatment. The NS + VPA group demonstrated significantly decreased neurologic impairment and faster speed of recovery as well as smaller brain lesion size compared with the NS group. Although the final cognitive function scores were similar between the groups, the VPA-treated animals reached the goal significantly faster than the NS controls. CONCLUSION: In this long-term survival model of TBI + HS, addition of low-dose VPA to saline resuscitation resulted in attenuated neurologic impairment, faster neurologic recovery, smaller brain lesion size, and a quicker normalization of cognitive functions.