Interrater Reliability of the Wolf Motor Function Test–Functional Ability Scale: Why It Matters

Background. One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. Objective. This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)–Functional Ability Scale (FAS). Methods. The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. Results. After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). Conclusions and Implications. A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone

Spontaneous Eosinophilic Nasal Inflammation in a Genetically-Mutant Mouse: Comparative Study with an Allergic Inflammation Model

Background: Eosinophilic inflammation is a hallmark of chronic rhinosinusitis with nasal polyps. To model this disease process experimentally, nasal sensitization of mice with ovalbumin or aspergillus has been described. Here, we describe a genetically mutant mouse that develops robust spontaneous nasal eosinophilic inflammation. These mice lack the enzyme SHP-1 that down-regulates the IL-4Ra/stat6 signaling pathway. We compared nasal inflammation and inflammatory mediators in SHP-1 deficient mice (mev) and an ovalbumin-induced nasal allergy model. Methods: A novel technique of trans-pharyngeal nasal lavage was developed to obtain samples of inflammatory cells from the nasal passages of allergic and mev mice. Total and differential cell counts were performed on cytospin preparations. Expression of tissue mRNA for IL-4, IL-13, and mouse beta-defensin-1 (MBD-1) was determined by quantitative PCR. Eotaxin in the lavage fluid was assessed by ELISA. Results: Allergic and mev mice had increased total cells and eosinophils compared with controls. Expression of IL-4 was similarly increased in both allergic and mev mice, but expression of IL-13 and eotaxin was significantly greater in the allergic mice than mev mice. Eotaxin was significantly up-regulated in both allergic rhinitis and mev mice. In both models of eosinophilic inflammation, down-regulation of the innate immune marker MBD-1 was observed. Conclusions: The mev mice display spontaneous chronic nasal eosinophilic inflammation with potential utility for chroni

Reduced Upper Limb Recovery in Subcortical Stroke Patients With Small Prior Radiographic Stroke

Background: Research imaging costs limit lesion-based analyses in already expensive large stroke rehabilitation trials. Despite the belief that lesion characteristics influence recovery and treatment response, prior studies have not sufficiently addressed whether lesion features are an important consideration in motor rehabilitation trial design.Objective: Using clinically-obtained neuroimaging, evaluate how lesion characteristics relate to upper extremity (UE) recovery and response to therapy in a large UE rehabilitation trial.Methods: We reviewed lesions from 297 participants with mild-moderate motor impairment in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study and their association with motor recovery, measured by the UE Fugl-Meyer (UE-FM). Significant lesion features identified on correlational and bivariate analysis were further analyzed for associations with recovery and therapy response using longitudinal mixed models.Results: Prior radiographic stroke was associated with less recovery on UE-FM in participants with motor impairment from subsequent subcortical stroke (−5.8 points) and in the overall sample (−3.6 points), but not in participants with cortical or mixed lesions. Lesion volume was also associated with less recovery, particularly after subcortical stroke. Every decade increase in age was associated with 1 less point of recovery on UE-FM. Response to specific treatment regimens varied based on lesion characteristics. Subcortical stroke patients experienced slightly less recovery with higher doses of upper extremity task-oriented training. Participants with cortical or mixed lesions experienced more recovery with higher doses of usual and customary therapy. Other imaging features (leukoaraiosis, ischemic vs. hemorrhagic stroke) were not significant.Conclusions: ICARE clinical imaging revealed information useful for UE motor trial design: stratification of persons with and without prior radiographic stroke may be required in participants with subcortical stroke, the majority of motor rehabilitation trial participants. Most of the prior radiographic strokes were small and cortically-based, suggesting even minor prior brain injury remote to the acute stroke lesion may limit spontaneous and therapy-related recovery. Lesion location may be associated with response to different therapy regimens, but the effects are variable and of unclear significance

Late maxillary protraction in patients with unilateral cleft lip and palate : a retrospective study

Objectives: This retrospective study assessed the dentoskeletal effect of late maxillary protraction (LMP; reverse-pull headgear, Class III elastics, and maxillary sutural loosening) in unilateral cleft lip and palate (UCLP) patients versus a control group of untreated UCLP patients. Materials and Methods: Cephalograms taken at age 13 to 14 years (T1) and 17 to 18 years (T2) were used for this study. The study group comprised 18 patients (10 male and 8 female, mean age at start of LMP therapy = 13.4 [0.45] years). A control groups of 17 patients (8 male and 9 female, mean age = 13.5 [0.44] years) was used for comparison. Results: The repeated-measures analysis of variance showed statistically significant changes across time between groups for the following variables (mean difference [T2-T1] in the study group, 95% confidence interval): SNA (°) (1.95, 0.75 to 3.15), A ⊥ Na Perp (mm) (1.82, 0.86 to 2.77), CoA (mm) (2.92, 1.53 to 4.31), ANB (°) (3.13, 2.02 to 4.24), Wits (mm) (7.82, 5.01 to 10.54), Mx-Md Diff (mm) (0.62, -1.58 to 2.83), Occl P-SN (°) (-3.98, -5.99 to -1.98), overjet (mm) (8.82, 5.90 to 11.74), FMIA (°) (4.05, -0.05 to 8.15), and IMPA (°) (-5.77, -9.74 to -1.80). Late maxillary protraction created a slight open bite (0.66 mm). Trends for overeruption of mandibular incisors and an increase in lower face height (P = .07 for both) were noted in the study group. Conclusions: Late maxillary protraction produced a combination of skeletal changes (protraction of maxilla, improvement in the maxillo-mandibular skeletal relationship) and dental compensations (counterclockwise rotation of occlusal plane, retroclination of mandibular incisors) in patients with UCLP. Late maxillary protraction was also associated with some unwanted tooth movements (open bite tendency, mandibular incisors overeruption)

Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction.

Etiology is unknown in the majority of individuals with autism spectrum disorder (ASD). One strategy to investigate pathogenesis is to stratify this heterogeneous disorder based on a prominent phenotypic feature that enriches for homogeneity within population strata. Co-occurring gastrointestinal dysfunction (GID) characterizes a subset of children with ASD. Our current objective was to investigate a potential pathophysiological measure to test the hypothesis that children with both ASD and GID have a more severe metabolic dysfunction than children with ASD-only, given that the highly metabolically active brain and gastrointestinal system may additively contribute measurable impairment. Plasma levels of F2t-Isoprostanes (F2-IsoPs), a gold standard biomarker of oxidative stress, were measured in 87 children in four groups: ASD-GID, ASD-only, GID-only and Unaffected. F2-IsoP levels were elevated in all 3 clinical groups compared to the Unaffected group, with the ASD-GID group significantly elevated above the ASD-only group (mean, SD in pg/mg: ASD-GID 53.6, 24.4; ASD-only 36.5, 13.3; p = 0.007). Adjusting for age, sex, and triglyceride levels, F2-IsoP levels remained significantly different between study groups, with a moderate effect size of η(p)(2) = 0.187 (p = 0.001). Elevation in peripheral oxidative stress is consistent with, and may contribute to, the more severe functional impairments in the ASD-GID group. With unique medical, metabolic, and behavioral features in children with ASD-GID, the present findings serve as a compelling rationale for both individualized approaches to clinical care and integrated studies of biomarker enrichment in ASD subgroups that may better address the complex etiology of ASD

Long-term endoscopic management for primary recurrent pyogenic cholangitis

Background: Primary recurrent pyogenic cholangitis (RPC) is characterized by relentless suppurative cholangitis in those with a suspected parasitic injury of the biliary tree. Prior work has demonstrated that the infections recur following “definitive” biliary surgery and long-term percutaneous biliary catheters are poorly tolerated. The aim of this study was to assess whether scheduled surveillance endoscopic retrograde cholangiopancreatography (ERCP) prevents cholangitis in those with RPC. Materials and Methods: Following initial biliary decompression and stone clearance, patients with RPC were offered serial ERCP every 3-6 months to remove accumulating stony debris and to dilate incipient strictures. Review of a large series managed using this approach at the University of California, San Francisco Medical Center was performed. The principle outcome was the development of acute cholangitis requiring hospitalization and whether the episode occurred, while the RPC patient was in compliance with endoscopic surveillance recommendations. Results: Over a period of 10 years, 66 patients with primary RPC were managed for RPC at the University of California, San Francisco. The patients were comprised primarily of first-generation immigrants from Asia though one-quarter had migrated from Latin America and Russia. Episodes of cholangitis were significantly less likely to occur in those undergoing surveillance biliary endoscopy than in those who were not (odds ratio 5.3; P = 0.005). The mean follow-up was 36.1 months. Conclusions: Serial endoscopic treatment of RPC may be used to systematically clear biliary debris and decreases the risk of cholangitis requiring hospitalization. It represents a reasonable initial management strategy for these patients. Surgery and percutaneous management may also be required, but are best performed as part of a multidisciplinary approach

A Novel Mechanism of Increased Infections in Contact Lens Wearers

The authors have identified a molecular mechanism that may be the underlying cause of the increase in corneal damage and infection observed in contact lens wearers. The data highlight the biological and financial potential for better contact lens solutions