Early diagnosis of persons with von Willebrand disease using a machine learning algorithm and real-world data.

BACKGROUND: Von Willebrand disease (VWD) is underdiagnosed, often delaying treatment. VWD claims coding is limited and includes no severity qualifiers; improved identification methods for VWD are needed. The aim of this study is to identify and characterize undiagnosed symptomatic persons with VWD in the US from medical insurance claims using predictive machine learning (ML) models. RESEARCH DESIGN AND METHODS: Diagnosed and potentially undiagnosed VWD cohorts were defined using Komodo longitudinal US claims data (January 2015-March 2020). ML models were built using key characteristics predictive of VWD diagnosis from the diagnosed cohort. Two ML models predicted VWD diagnosis with the highest accuracy in females (random forest; 84%) and males (gradient boosting machine; 85%). Undiagnosed persons suspected to have VWD were identified using an 80% cutoff probability; profiles of key characteristics were constructed. RESULTS: The trained ML models were applied to the undiagnosed cohort (28,463 females; 20,439 males) with suspected VWD. Fifty-two percent of undiagnosed females had heavy menstrual bleeding, a key pre-diagnosis symptom. Undiagnosed males tended to have more frequent medical procedures, hospitalizations, and emergency room visits compared with undiagnosed females. CONCLUSIONS: ML algorithms successfully identified potentially undiagnosed symptomatic people with VWD, although many may remain undiagnosed and undertreated. External validation of the algorithms is recommended.

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.

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.

Broad Coverage Precoding for 3D Massive MIMO with Huge Uniform Planar Arrays.

In this paper, we propose a novel broad coverage precoder design for three-dimensional (3D) massive multi-input multi-output (MIMO) equipped with huge uniform planar arrays (UPAs). The desired two-dimensional (2D) angle power spectrum is assumed to be separable. We use the per-antenna constant power constraint and the semi-unitary constraint which are widely used in the literature. For normal broad coverage precoder design, the dimension of the optimization space is the product of the number of antennas at the base station (BS) and the number of transmit streams. With the proposed method, the design of the high-dimensional precoding matrices is reduced to that of a set of low-dimensional orthonormal vectors, and of a pair of low-dimensional vectors. The dimensions of the vectors in the set and the pair are the number of antennas per column and per row of the UPA, respectively. We then use optimization methods to generate the set of orthonormal vectors and the pair of vectors, respectively. Finally, simulation results show that the proposed broad coverage precoding matrices achieve nearly the same performance as the normal broad coverage precoder with much lower computational complexity.

The cellular and circuit basis for evolutionary change in sensory perception in mormyrid fishes.

Species differences in perception have been linked to divergence in gross neuroanatomical features of sensory pathways. The anatomical and physiological basis of evolutionary change in sensory processing at cellular and circuit levels, however, is poorly understood. Here, we show how specific changes to a sensory microcircuit are associated with the evolution of a novel perceptual ability. In mormyrid fishes, the ability to detect variation in electric communication signals is correlated with an enlargement of the midbrain exterolateral nucleus (EL), and a differentiation into separate anterior (ELa) and posterior (ELp) regions. We show that the same cell types and connectivity are found in both EL and ELa/ELp. The evolution of ELa/ELp, and the concomitant ability to detect signal variation, is associated with a lengthening of incoming hindbrain axons to form delay lines, allowing for fine temporal analysis of signals. The enlargement of this brain region is also likely due to an overall increase in cell numbers, which would allow for processing of a wider range of timing information.