Reliability and Confidence of Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Rating Among Research and Clinical Speech Pathologists Before and After Implementation of a Training Manual: A Multi-site Study.

DIGEST is a validated, open-source method to grade the severity of pharyngeal dysphagia from the modified barium swallow (MBS) study. Dissemination and implementation of DIGEST is rising, making it critical to understand reliability and facilitators of accurate implementation among users. The aim was to assess reliability of the tool among speech-language pathology (SLP) raters practicing at multiple sites before and after review of a DIGEST training manual and evaluate confidence of DIGEST use pre-and post-training. Thirty-two SLPs from 5 sites participated in a blinded longitudinal DIGEST rating study. Raters were provided a standardized training set of MBS (n = 19). Initial SLP ratings (round 1, R1) were followed by a 2-4 week break before raters rated a re-keyed MBS set (round 2, R2). A minimum 4-8 week wash-out period then preceded self-study of the DIGEST training manual which was followed by a final rating (round 3, R3) and a post-manual survey afterwards. Baseline reliability (R1) of overall DIGEST was on average k = 0.70, reflecting agreement in the substantial range. Seventy-five percent of raters (24/32) demonstrated reliability ≥ 0.61 in the substantial to almost perfect range prior to training. Inter-rater reliability significantly improved from R1 to R3 after review of the DIGEST manual, with the largest change in DIGEST-Efficiency (mean change: DIGEST k = .04, p = .009, DIGEST-Safety k = .07, p = 0.03, and DIGEST-Efficiency k = .14, p = 0.009). Although DIGEST reliability at baseline was adequate in the majority of raters, self-study of the DIGEST training manual significantly improved inter-rater reliability and rater confidence using the DIGEST method, particularly when assigning DIGEST-Efficiency grade. These early data show promise that provider training may be useful to aid in fidelity of DIGEST implementation among SLP clinical users with varying DIGEST experience.

HIV and viral hepatitis coinfection analysis using surveillance data from 15 US states and two cities.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

A two phased study on health care professionals' perceptions of single or multi-use of intermittent catheters.

AIMS: This two phase study aimed to explore health care professionals' teaching and prescribing practice related to intermittent catheterisation and to identify their perceptions about the possible implementation of a mixed (single and multi-use) package for intermittent catheterization. INTRODUCTION: Single-use intermittent catheters are the norm in the UK although multi-use is common in some other countries. A recent Cochrane review found no difference in complications, including urinary tract infection rates, between those using single or multi-use catheters. A flexible option of both multi-use and single use intermittent catheters could provide users with more flexible choices in self-care. However, understanding health care professionals' perspectives is one of the keys to developing a multi-use intervention. DESIGN: A qualitative research framework using in-depth interviews to inform an on line survey. METHOD: In-depth interviews were conducted with health care professionals based in the UK who prescribe catheters, teach intermittent catheterisation or manage an intermittent catheterisation service. The interviewees were selected to represent a range of clinical areas, experience and professions - continence advisors, urology, multiple sclerosis (MS) and spinal cord injury specialist nurses, and General Practitioners. Following framework analysis the themes and factors identified were used to develop an on-line survey which was disseminated through health care professional networks whose members saw patients who use intermittent catheters. RESULTS: Nineteen health care professionals participated in the telephone interviews; 206 completed the survey. A wide range of professionals in terms of experience and specialty afforded rich information regarding the contextual issues around the teaching and prescribing of intermittent catheters. The primary finding was that health care professionals were concerned about 'minimising health risk' and maximising 'normalcy' for those using intermittent self-catheterisation. Health care professionals who worked in the acute setting or had no experience of re-use were most resistant to the re-use of catheters. Professionals requested evidence that a multi-use package would not increase the risk of developing a urinary tract infection or increase the burden of use to a patient before a mixed package would be considered. CONCLUSIONS: For multi-use to be acceptable, evidence based guidelines must be available for healthcare professionals and cleaning methods must be acceptable and safe for intermittent catheter users. Further evidence may be required to establish that a mixed catheter package is equivalent to single use only, particularly for outcomes such as urinary tract infection, urethral injury and quality of life. RELEVANCE TO CLINICAL PRACTICE: This paper highlights that if multi-use catheters are to be successfully introduced into clinical practice, the ease of use, safety and effectiveness of the cleaning technique will need to be convincingly demonstrated by a range of well-defined users.

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.

My Life in Clinical Neuroscience: The Beginning.

This chapter recounts the author's life from childhood until he opened his research laboratory as an Assistant Professor in the Department of Pharmacology and Experimental Therapeutics at Johns Hopkins School of Medicine in 1976. It emphasizes the importance of chance opportunities and generous mentoring in the initiation of his career in neuroscience and psychiatric research.

UT-B Urea Transporter Localization in the Bovine Gastrointestinal Tract.

Facilitative UT-B urea transporters play an important role in the urea nitrogen salvaging process that occurs in the gastrointestinal tract of mammals, particularly ruminants. Gastrointestinal UT-B transporters have previously been reported in various ruminant species-including cow, sheep and goat. In this present study, UT-B transporter localization was investigated in tissues throughout the bovine gastrointestinal tract. RT-PCR analysis showed that UT-B2 was the predominant UT-B mRNA transcript expressed in dorsal, ventral and cranial ruminal sacs, while alternative UT-B transcripts were present in other gastrointestinal tissues. Immunoblotting analysis detected a strong, glycosylated ~50 kDa UT-B2 protein in all three ruminal sacs. Immunolocalization studies showed that UT-B2 protein was predominantly localized to the plasma membrane of cells in the stratum basale layer of all ruminal sac papillae. In contrast, other UT-B protein staining was detected in the basolateral membranes of the surface epithelial cells lining the abomasum, colon and rectum. Overall, these findings confirm that UT-B2 cellular localization is similar in all ruminal sacs and that other UT-B proteins are located in epithelial cells lining various tissues in the bovine gastrointestinal tract.

Harmonization of detailed clinical models with clinical study data standards.

INTRODUCTION: This article is part of the Focus Theme of METHODS of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: Data sharing and integration between the clinical research data management system and the electronic health record system remains a challenging issue. To approach the issue, there is emerging interest in utilizing the Detailed Clinical Model (DCM) approach across a variety of contexts. The Intermountain Healthcare Clinical Element Models (CEMs) have been adopted by the Office of the National Coordinator awarded Strategic Health IT Advanced Research Projects for normalization (SHARPn) project for normalizing patient data from the electronic health records (EHR). OBJECTIVE: The objective of the present study is to describe our preliminary efforts toward harmonization of the SHARPn CEMs with CDISC (Clinical Data Interchange Standards Consortium) clinical study data standards. METHODS: We were focused on three generic domains: demographics, lab tests, and medications. We performed a panel review on each data element extracted from the CDISC templates and SHARPn CEMs. RESULTS: We have identified a set of data elements that are common to the context of both clinical study and broad secondary use of EHR data and discussed outstanding harmonization issues. CONCLUSIONS: We consider that the outcomes would be useful for defining new requirements for the DCM modeling community and ultimately facilitating the semantic interoperability between systems for both clinical study and broad secondary use domains.

Impact of reducing the threshold for acetylcysteine treatment in acute paracetamol poisoning: the recent United Kingdom experience.

BACKGROUND: On 3 September 2012, the licensed indication for acetylcysteine was changed in the United Kingdom (UK) so that all patients with a plasma paracetamol concentration above a "100 mg/L" (4 h post ingestion) nomogram treatment line after an acute paracetamol (acetaminophen) overdose should be treated. This is a lower threshold than that used in the United States, Canada, Australia, and New Zealand. Here we report the impact of this change in the UK on the management of patients with acute overdose in different paracetamol concentration ranges. METHODS: This is a cohort study, consisting of a retrospective analysis conducted on prospectively collected audit data in three UK hospitals. Following appropriate ethical and data protection authority approval, data for patients presenting within 24 h of an acute timed single paracetamol overdose were extracted. Numbers of admissions and use of antidote in relation to different paracetamol concentration bands (< 100 mg/L; 100-149 mg/L; 150-199 mg/L; and ≥ 200 mg/L at 4 h) were analyzed for one-year periods before and after the change. RESULTS: Comparing the year before with the year after the change, there was no change in the numbers of patients presenting to hospital within 24 h of acute timed paracetamol overdose (1246 before and 1251 after), but more patients were admitted (759 before and 849 after) and treated with acetylcysteine (389 before and 539 after). Of the 150 additional patients treated with acetylcysteine in the year following the change, 114 (76%, 95% CI: 68.4-82.6) were in the 100-149 group and 9 (6.0%, 95% CI: 2.8-11.1) in the 150-199 group. CONCLUSIONS: Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100-149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions.

The effects of increased fluid viscosity on stationary characteristics of EEG signal in healthy adults.

Electroencephalography (EEG) systems can enable us to study cerebral activation patterns during performance of swallowing tasks and possibly infer about the nature of abnormal neurological conditions causing swallowing difficulties. While it is well known that EEG signals are non-stationary, there are still open questions regarding the stationarity of EEG during swallowing activities and how the EEG stationarity is affected by different viscosities of the fluids that are swallowed by subjects during these swallowing activities. In the present study, we investigated the EEG signal collected during swallowing tasks by collecting data from 55 healthy adults (ages 18-65). Each task involved the deliberate swallowing of boluses of fluids of different viscosities. Using time-frequency tests with surrogates, we showed that the EEG during swallowing tasks could be considered non-stationary. Furthermore, the statistical tests and linear regression showed that the parameters of fluid viscosity, sex, and different brain regions significantly influenced the index of non-stationarity values. Therefore, these parameters should be considered in future investigations which use EEG during swallowing activities.

Excessive gestational weight gain over multiple pregnancies and the prevalence of obesity at age 40.

OBJECTIVE: Although several studies have found an association between excessive gestational weight gain (GWG) and obesity later in life, to the best of our knowledge, no studies have explored the role of GWG events across the life course. DESIGN AND METHODS: We describe how the prevalence of midlife obesity (BMI⩾30 at age 40 or 41) among women varies by life course patterns of GWG (using 2009 IOM guidelines) in the USA's National Longitudinal Survey of Youth 1979 cohort. RESULTS: Among women who reported 1-3 births before age 40, the prevalence of midlife obesity increased with a rising number of excessive GWG events: from none (23.4%, n=875) to one (37.6%, n=707), from none (23.4%, n=875) to two (46.8%, n=427) and from none (23.4%, n=875) to three (54.6%, n=108), P<0.00005 for trend. Obesity prevalence was similar for the same number of excessive GWG events, regardless of parity. No clear pattern emerged for the sequencing of excessive GWG event(s) and later obesity. CONCLUSIONS: In our descriptive exploratory study, excessive GWG events appear to be associated with increased prevalence of obesity for parous women, suggesting the importance of preventive interventions regardless of timing of pregnancy-related weight changes over the life course.

Baseline characteristics of cervical auscultation signals during various head maneuvers.

Cervical auscultation (CA) is an emerging method of assessing swallowing disorders that is both non-invasive and inexpensive. This technique utilizes microphones to detect acoustic sounds produced by swallowing activity and characterize its behavior. Though some properties of swallowing sounds are known, there is still a need for a complete understanding of the baseline characteristics of cervical auscultation signals as well as how they change due to the patient's head motion, age, and sex. In order to examine these parameters, data was collected from 56 healthy adult participants that performed six different head movement tasks without swallowing. After preprocessing the signal, features were extracted. Dependent variables were time domain, frequency domain and time-frequency domain features. Statistical tests showed that only the skewness and peak frequency were not statistically different for all tasks. The peak frequency results indicate that head movement does not significantly affect the microphone signal, and that it is unnecessary to filter out the lowest frequency components. No sex differences were observed in the extracted features, but several features exhibited age dependence.

MRI characteristics of nodular fasciitis of the musculoskeletal system.

OBJECTIVE: To evaluate MRI imaging appearances of nodular fasciitis in a pathologic-proven series of 29 patients. MATERIALS AND METHODS: Review of the orthopedic oncology and pathology databases yielded 51 cases of histologically proven nodular fasciitis. MR imaging was available in 29 patients. Three musculoskeletal radiologists retrospectively reviewed all cases in consensus. Imaging features evaluated included location in the body, size, compartmental localization, relationship to fascia, signal characteristics, enhancement pattern, transcompartmental extension, and osseous and intra-articular involvement. RESULTS: There were 15 male and 14 female patients. Mean age was 33 years (range, 16-59 years). Lesions ranged in size from 1.6 to 9 cm with 84 % of lesions measuring less than 4 cm. Twenty-three lesions were located in the upper arm or shoulder girdle. Nine lesions were subcutaneous in location, nine were intra-muscular, and 11 were inter-muscular. Lesions were consistently ovoid in shape with broad fascial contact. They exhibited internal homogenous low T1 and heterogeneous intermediate T2 signal with surrounding edema and slightly inhomogeneous enhancement. Twelve lesions exhibited central non-enhancing areas. Trans-compartmental spread was demonstrated in nine lesions. Osseous changes were seen in five cases and included extrinsic cortical saucerization, medullary edema, and transcortical osseous invasion. Two lesions demonstrated intra-articular extension. CONCLUSIONS: MR imaging features of nodular fasciitis are generally non-specific and can be mistaken for a soft tissue sarcoma. This series, the largest MRI series of musculoskeletal cases in the literature, confirms the predilection of nodular fasciitis for the upper extremity in young adults but also demonstrates that aggressive imaging features such as transcompartmental spread, and osseous and intra-articular involvement may be seen in association with this benign soft tissue lesion.

Enhanced local processing of dynamic visual information in autism: evidence from speed discrimination.

An important issue for understanding visual perception in autism concerns whether individuals with this neurodevelopmental disorder possess an advantage in processing local visual information, and if so, what is the nature of this advantage. Perception of movement speed is a visual process that relies on computation of local spatiotemporal signals but requires the comparison of information from more than a single spatial location or temporal point. This study examined speed discrimination in adolescents (ages 13-18 years old) with autism spectrum disorders (ASD). Compared to healthy controls (n=17), individuals with ASD (n=19) showed similarly precise speed discrimination when two comparison motion stimuli (random dot patterns) were presented closely in time (0.5s). With a longer temporal interval (3s) between the motion stimuli, individuals with ASD outperformed healthy controls on speed discrimination. On a second task--global motion perception--in which individuals were asked to detect coherent motion, individuals with ASD exhibited slightly degraded performance levels. The observed temporally selective enhancement in speed discrimination indicates that a local processing advantage in autism develops over a longer temporal range and is not limited to the spatial domain. These results suggest a dynamic perceptual mechanism for understanding, and therapeutically addressing, atypical visual processing in this neurodevelopmental disorder.

Abnormal visual experiences in individuals with histories of hallucinogen use: a Web-based questionnaire.

Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study.

Serine racemase deletion disrupts memory for order and alters cortical dendritic morphology.

There is substantial evidence implicating N-methyl-D-aspartate receptors (NMDARs) in memory and cognition. It has also been suggested that NMDAR hypofunction might underlie the cognitive deficits observed in schizophrenia as morphological changes, including alterations in the dendritic architecture of pyramidal neurons in the prefrontal cortex (PFC), have been reported in the schizophrenic brain post mortem. Here, we used a genetic model of NMDAR hypofunction, a serine racemase knockout (SR-/-) mouse in which the first coding exon of the mouse SR gene has been deleted, to explore the role of D-serine in regulating cognitive functions as well as dendritic architecture. SR-/- mice exhibited a significantly disrupted representation of the order of events in distinct experiences as showed by object recognition and odor sequence tests; however, SR-/- animals were unimpaired in the detection of novel objects and in spatial displacement, and showed intact relational memory in a test of transitive inference. In addition, SR-/- mice exhibited normal sociability and preference for social novelty. Neurons in the medial PFC of SR-/- mice displayed reductions in the complexity, total length and spine density of apical dendrites. These findings show that D-serine is important for specific aspects of cognition, as well as in regulating dendritic morphology of pyramidal neurons in the medial PFC (mPFC). Moreover, they suggest that NMDAR hypofunction might, in part, be responsible for the cognitive deficits and synaptic changes associated with schizophrenia, and highlight this signaling pathway as a potential target for therapeutic intervention.

A randomized, placebo-controlled trial of sustained-release dextroamphetamine for treatment of methamphetamine addiction.

Sixty treatment-seeking individuals with methamphetamine (MA) dependence entered a randomized, placebo-controlled, double-blind clinical trial of oral dextroamphetamine (d-AMP) as a replacement therapy for MA dependence. The subjects took 60 mg sustained-release d-AMP for 8 weeks, during which time they received eight 50-min sessions of individual psychotherapy. Adverse events and urine toxicology for MA were assessed two times a week. There were no serious adverse events. Urine samples containing <1,000 ng/ml of MA were classified as negative for MA. The MA-negative scores in the d-AMP group (3.1 ± SD 4.6) were no higher than those in the placebo group (3.3 ± SD 5.3; P > 0.05). However, withdrawal and craving scores were significantly lower in the d-AMP group (P < 0.05 for both). Although subjects taking d-AMP did not reduce their use of MA, the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d-AMP as a pharmacologic intervention for MA dependence, possibly at higher doses.

Tracheo-oesophageal fistula diagnosed with multidetector computed tomography.

This case highlights important issues in investigation of patients with suspected tracheo-oesophageal fistula including the value of multidetector computed tomography, the importance of thorough imaging evaluation when high clinical suspicion of tracheo-oesophageal fistula exists and the value of close interaction between radiologists and intensive care physicians in the investigation of these patients.

Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.

Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior.

A subset of glutamate receptors that are specifically sensitive to the glutamate analog N-methyl-D-aspartate (NMDA) are molecular coincidence detectors, necessary for activity-dependent processes of neurodevelopment and in sensory and cognitive functions. The activity of these receptors is modulated by the endogenous amino acid D-serine, but the extent to which D-serine is necessary for the normal development and function of the mammalian nervous system was previously unknown. Decreased signaling at NMDA receptors has been implicated in the pathophysiology of schizophrenia based on pharmacological evidence, and several human genes related to D-serine metabolism and glutamatergic neurotransmission have been implicated in the etiology of schizophrenia. Here we show that genetically modified mice lacking the ability to produce D-serine endogenously have profoundly altered glutamatergic neurotransmission, and relatively subtle but significant behavioral abnormalities that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety.