Identifying perianal fistula complications in pediatric patients with Crohn's disease using administrative claims.

BACKGROUND: Although perianal fistulas occur commonly in pediatric Crohn's disease (CD), evaluations of health services have been limited since no validated claims-based methods exist for identifying cases. OBJECTIVE: To develop and validate accurate case definitions for perianal fistulas among pediatric patients with CD from administrative claims. METHODS: Retrospective cohort study in which we developed and tested candidate case definitions for perianal fistula. Patients (age 5-21 years between 2005-2012) with CD enrolled in Michigan Medicaid with healthcare at University of Michigan were identified via claims. Medical records were obtained from all identified patients, whose entire records were abstracted. Medical record evidence for perianal fistula was considered the "gold standard" against which candidate case definitions were compared. The reference case definition of perianal fistula (ICD9 565.1) and candidate case definitions were evaluated. RESULTS: Of 843 patients identified via claims, 274 (33%) met CD criteria for inclusion. The true perianal fistula rate among CD patients was 18% (n = 49). The top-performing candidate case definition identified 15% (n = 42), had sensitivity of 77.6%, specificity of 98.2%, positive predictive value (PPV) 90.5%, negative predictive value (NPV) 95.3%, and area under receiver operator characteristic curve (ROC) of 0.88. In contrast, the reference case definition identified 9% (n = 26), sensitivity 51.0%, specificity 99.6%, PPV 96.2%, NPV 90.3%, and had an area under ROC of 0.75. CONCLUSIONS: We demonstrated that it is feasible to use administrative claims data to accurately identify pediatric patients with perianal fistula complications. Claims-based case definitions were found to be highly accurate through medical record review, providing a high degree of confidence for future studies where chart review is not feasible. These claims-based methods can be applied to claims data in other settings for the evaluation of health services utilization as well as to assess the comparative effectiveness of prevention and treatment strategies.

ERP adaptation provides direct evidence for early mirror neuron activation in the inferior parietal lobule.

Mirror neuron systems are frequently investigated by assessing overlapping brain activity during observation and execution of actions; however, distinct neuronal subpopulations may be activated that fall below the spatial resolution of magnetic resonance techniques. This shortfall can be resolved using repetition suppression paradigms that identify physiological adaptation processes caused by repeated activation of identical neuronal circuits. Here, event-related potentials were used to investigate the time course of mirror neuron circuit activation using repetition suppression within and across action observation and action execution modalities. In a lip-reading and speech production paradigm, the N170 component indexed stimulus repetition by adapting to both cross-modal and intra-modal repetitions in the left hemisphere. Neuronal source localization revealed activation of the left inferior parietal lobule during cross-modal relative to intra-modal trials. These results provide support for the position that the same neuronal circuits are activated in perceiving and performing articulatory actions. Moreover, our data strongly suggest that inferior parietal lobule mirror neurons are activated relatively early in time, which indicates partly automatic processes of linguistic perception and mirroring. Repetition suppression paradigms therefore help to elucidate neuronal correlates of different cognitive processes and may serve as a starting point for advanced electrophysiological research on mirror neurons.

Evidence for impaired visual prediction error in schizophrenia.

BACKGROUND: Mismatch negativity (MMN) is regarded a prediction error signal that is deficient in schizophrenia in the auditory modality. If, however, MMN reflects a general computational signal of the cortex, then MMN should be also deficient in the visual modality in schizophrenia patients. METHODS: Twenty-two schizophrenia patients and 24 matched healthy controls finished a visual oddball task while high-density electroencephalogram was recorded. Visual mismatch negativity was computed as a surrogate marker of prediction error. RESULTS: Visual MMN, as measured over posterior extra-striate cortical areas, was significantly reduced in schizophrenia at about 300 ms post stimulus. Standardized mean difference was -.98, corresponding to a large effect size. CONCLUSIONS: A posterior visual MMN deficit in schizophrenia is demonstrated for the first time. Our results tentatively suggest a supra-modal MMN deficit in schizophrenia and thus argue in favor of reduced prediction error estimation in schizophrenia.

Effects of intranasal oxytocin prior to encoding and retrieval on recognition memory.

RATIONALE: The neuropeptide oxytocin (OXT) has been shown to modulate a variety of human social behaviors. However, little is known about its impact on emotional memory processing. Previous research demonstrated both memory-enhancing and memory-impairing oxytocinergic effects. METHODS: We investigated the influence of a single (prior to encoding) and a repeated (prior to encoding and retrieval) intranasal administration of OXT on recognition memory for stimuli taken from the International Affective Picture System. In addition, we assessed the interaction of emotion regulation during encoding and OXT-induced memory effects. In a double-blind, placebo-controlled design, 80 healthy young males performed an emotion regulation task followed by a surprising recognition memory task after 60 min. RESULTS: Results show that repeated OXT administration significantly improved memory certainty for negative social stimuli. Regarding the influence of emotion regulation, the promnestic effect of OXT was more pronounced when participants had been instructed to increase their negative emotions during encoding. CONCLUSIONS: Our findings indicate that OXT facilitates the processing of negative social stimuli during memory encoding and retrieval, possibly by enhancing the perception of aversive aspects in social situations.

Exploring the time course of N170 repetition suppression: a preliminary study.

Several studies employed the repetition suppression paradigm to investigate the face-specific N170 component of the event-related potential (ERP), but yielded highly inconsistent results. Varying inter-stimulus intervals (ISIs) may account for inconsistencies between studies. This study aimed at exploring the time course of repetition suppression by systematically investigating the association between ISI and ERP adaptation. Fourteen healthy subjects were investigated with a passive face recognition paradigm using paired stimuli. Stimuli were presented for 500ms and ISIs parametrically varied between 400 and 2000ms. N170 was constructed to investigate adaptation effects on the level of perceptual face processing. We found an evidence for an asymptotic decay of repetition suppression over time with significant N170 adaptation effects only after the shortest ISI. Our results robustly demonstrate that N170 adaptation in a paired stimulus protocol critically depends on short ISIs, thereby explaining the inconsistencies observed in the previous studies. For future social cognition studies using neuronal adaptation to face stimuli, the current results provide a well defined ISI associated with a large N170 adaptation effect.

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes.

A series of di-, tri- and tetravalent axles and wheels for the synthesis of pseudorotaxanes bearing the tetralactam macrocycle/diamide axle binding motif was prepared. Starting from iodinated monovalent precursors, Sonogashira cross-coupling reactions were utilized to couple the binding sites to appropriate spacer groups. Through this "Lego" or "toolbox" approach, the convergent synthesis of host and guests with a well-defined number of the binding sites is possible. In addition, the spatial arrangement of the binding sites can be controlled through the quite rigid connections between linker and binding sites. Although a quantitative assessment of binding strengths was not possible by NMR titration experiments, typical and significant shifts of the signals of the diamide moiety indicate qualitatively the formation of pseudorotaxanes from the axle and wheel precursors.