Using Unique Abilities to Capitalize on a Failed Clinical Informationist Project

PowerPoint slides from a presentation given at SCC/MLA 2010.

Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?

BACKGROUND: Virtual reality testing of everyday activities is a novel type of computerized assessment that measures cognitive, executive, and motor performance as a screening tool for early dementia. This study used a virtual reality day-out task (VR-DOT) environment to evaluate its predictive value in patients with mild cognitive impairment (MCI). METHODS: One hundred thirty-four patients with MCI were selected and compared with 75 healthy control subjects. Participants received an initial assessment that included VR-DOT, a neuropsychological evaluation, magnetic resonance imaging (MRI) scan, and event-related potentials (ERPs). After 12 months, participants were assessed again with MRI, ERP, VR-DOT, and neuropsychological tests. RESULTS: At the end of the study, we differentiated two subgroups of patients with MCI according to their clinical evolution from baseline to follow-up: 56 MCI progressors and 78 MCI nonprogressors. VR-DOT performance profiles correlated strongly with existing predictive biomarkers, especially the ERP and MRI biomarkers of cortical thickness. CONCLUSIONS: Compared with ERP, MRI, or neuropsychological tests alone, the VR-DOT could provide additional predictive information in a low-cost, computerized, and noninvasive way.

Emergency stabilization of the pelvic ring: Clinical comparison between three different techniques

Background: Emergency devices for pelvic ring stabilization include circumferential sheets, pelvic binders, and c-clamps. Our knowledge of the outcome of these techniques is currently based on limited information. Methods: Using the dataset of the German Pelvic Trauma Registry, demographic and injury-associated characteristics as well as the outcome of pelvic fracture patients after sheet, binder, and c-clamp treatment was compared. Outcome parameters included transfusion requirement of packed red blood cells, length of hospital stay, mortality, and incidence of lethal pelvic bleeding. Results: Two hundred seven of 6137 (3.4%) patients documented in the German Pelvic Trauma Registry between April 30th 2004 and January 19th 2012 were treated by sheets, binders, or c-clamps. In most cases, c-clamps (69%) were used, followed by sheets (16%), and binders (15%). The median age was significantly lower in patients treated with binders than in patients treated with sheets or c-clamps (26 vs. 47 vs. 42 years, p = 0.01). Sheet wrapping was associated with a significantly higher incidence of lethal pelvic bleeding compared to binder or c-clamp stabilization (23% vs. 4% vs. 8%). No significant differences between the study groups were found in sex, fracture type, blood haemoglobin concentration, arterial blood pressure, Injury Severity Score, the incidence of additional pelvic packing and arterial embolization, need of red blood cell transfusion, length of hospitalisation, and mortality. Conclusions: The data suggest that emergency stabilization of the pelvic ring by binders and c-clamps is associated with a lower incidence of lethal pelvic bleeding compared to sheet wrapping.

Potentials and pitfalls of clinical peptidomics and metabolomics

Clinical peptidomics and metabolomics are two emerging "-omics" technologies with the potential not only to detect disease-specific markers, but also to give insight into the disease dependency of degradation processes and metabolic pathway alterations. However, despite their rapid evolution and major investments, a clinical breakthrough, such as the approval of a major cancer biomarker, is still out of sight. What are the reasons for this failure? In this review we focus on three important factors: sensitivity, specificity and the avoidance of bias. The way to clinical implementation of peptidomics and metabolomics is still hampered by many of the problems that had to be solved for genomics and proteomics in the past, as well as new ones that require the creation of new analytic, computational and interpretative techniques. The greatest challenge, however, will be the integration of information from different "-omics" subdisciplines into straightforward answers to clinical questions, for example, in the form of new, superior "meta-markers".

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications.

Owner-reported coughing and nasal discharge are associated with clinical findings, arterial oxygen tension, mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting.

REASONS FOR PERFORMING STUDY In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). OBJECTIVES To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. STUDY DESIGN Cross-sectional study comparing healthy and RAO-affected horses. METHODS Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing frequency' and 'nasal discharge'. Differences between these groups were examined using clinical examination, blood gas analyses, endoscopic mucus scores, cytology of tracheobronchial secretion and bronchoalveolar lavage fluid, and airway hyperresponsiveness determined by plethysmography with histamine bronchoprovocation. RESULTS Frequently coughing horses differed most markedly from healthy control animals. Histamine bronchoprovocation-derived parameters were significantly different between the healthy control group and all RAO groups. Mucus grades and tracheobronchial secretion and bronchoalveolar lavage fluid neutrophil percentages had particularly high variability, with overlap of findings between groups. Owner satisfaction with the clinical status of the horse was high, even in severely affected horses. CONCLUSIONS Owner-reported coughing and nasal discharge are associated with specific clinical and diagnostic findings in RAO-affected horses in field settings. While airway hyperresponsiveness differentiates best between healthy horses and asymptomatic RAO-affected horses, the absence of coughing and nasal discharge does not rule out significant neutrophilic airway inflammation. Owner satisfaction with the clinical status of the horse was uninformative.

Spatial cognition, body representation and affective processes: the role of vestibular information beyond ocular reflexes and control of posture

A growing number of studies in humans demonstrate the involvement of vestibular information in tasks that are seemingly remote from well-known functions such as space constancy or postural control. In this review article we point out three emerging streams of research highlighting the importance of vestibular input: (1) Spatial Cognition: Modulation of vestibular signals can induce specific changes in spatial cognitive tasks like mental imagery and the processing of numbers. This has been shown in studies manipulating body orientation (changing the input from the otoliths), body rotation (changing the input from the semicircular canals), in clinical findings with vestibular patients, and in studies carried out in microgravity. There is also an effect in the reverse direction; top-down processes can affect perception of vestibular stimuli. (2) Body Representation: Numerous studies demonstrate that vestibular stimulation changes the representation of body parts, and sensitivity to tactile input or pain. Thus, the vestibular system plays an integral role in multisensory coordination of body representation. (3) Affective Processes and Disorders: Studies in psychiatric patients and patients with a vestibular disorder report a high comorbidity of vestibular dysfunctions and psychiatric symptoms. Recent studies investigated the beneficial effect of vestibular stimulation on psychiatric disorders, and how vestibular input can change mood and affect. These three emerging streams of research in vestibular science are—at least in part—associated with different neuronal core mechanisms. Spatial transformations draw on parietal areas, body representation is associated with somatosensory areas, and affective processes involve insular and cingulate cortices, all of which receive vestibular input. Even though a wide range of different vestibular cortical projection areas has been ascertained, their functionality still is scarcely understood.

Mindfulness-based cognitive therapie for depression (MBCT) in clinical practice - baseline patient characteristics, process and outcome

Introduction: Mindfulness based cognitive therapy for depression (MBCT) has shown to be effective for the reduction of depressive relapse. However, additional information regarding baseline patient characteristics and process features related to positive response could be helpful both for the provision of MBCT in clinical practice, as well as for its further development. Method: Baseline characteristics, process data, and immediate outcome (symptom change, change in attitudes and trait mindfulness) of 108 patients receiving MBCT in routine care were recorded. A newly developed self-report measure (Daily Mindfulness Scale, DMS) was applied daily during the MBCT program. Additionally, patients filed daily reports on their mindfulness practice. There was no control group available. Results: Patients with more severe initial symptoms indicated greater amounts of symptom improvement, but did not show great rates of dropout from the MBCT intervention. Younger age was related to higher rates of dropout. Contradictory to some previous data, patients with lower levels of initial trait mindfulness showed greater improvement in symptoms, even after controlling for initial levels of symptoms. Adherence to daily mindfulness practice was high. Consistent with this result, the duration of daily mindfulness practice was not related to immediate outcome. Process studies using multivariate time series analysis revealed a specific role of daily mindfulness in reducing subsequent negative mood. Conclusions: Within the range of patient present in this study and the given study design, results support the use of MBCT in more heterogeneous groups. This demanding intervention was well tolerated by patients with higher levels of symptoms, and resulted in significant improvements regarding residual symptoms. Process-outcome analyses of initial trait mindfulness and daily mindfulness both support the crucial role of changes in mindfulness for the effects of MBCT.

Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment

Mast cells (MCs) are well known for their neoplastic transformation in solitary and multiple cutaneous mast cell tumours (MCTs), as well as visceral and systemic mastocytosis. Dogs have a unique risk of developing cutaneous MCTs, and they account for 7% to 21% of all canine skin tumours. The aetiology of canine MCTs is unknown but is probably multifactorial. This article reviews up-to-date knowledge on the pathogenesis, the clinical presentation, the clinical prognostic factors, the diagnostic workup including clinical staging, cytological findings, histological findings and the various grading systems which have been evaluated based on morphology, the assessment of proliferation markers and other factors such as vessel density. Furthermore, detailed information about current treatment protocols for canine cutaneous MCTs is provided.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

BackgroundHepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.MethodsVia questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.ResultsEarly treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 ¿M) and NTBC-levels in the therapeutic range (20¿40 ¿M). Side effects of NTBC are mild and often transient.Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).ConclusionBased on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Associations between the decrease in bovine clinical mastitis and changes in dairy farmers' attitude, knowledge, and behavior in the Netherlands.

The aim of this study was to associate changes in dairy farmers' self-reported attitude, knowledge, and behavior with the decrease in incidence rate of clinical mastitis (IRCM). Farmer-diagnosed clinical mastitis cases were obtained from two surveys conducted before (July 2004-June 2005) and at the end (2009) of a mastitis control program in the Netherlands. Information on farmers' attitude, knowledge, and behavior was also obtained by sending the farmers the same questionnaire during both surveys. Multivariable linear regression models identified that the herd level 2004 IRCM explained 28% of the variation in the decrease of IRCM. Changes in farmers' attitude and knowledge, and changes in farmers' behavior additionally explained 24% and 5%, respectively. These results suggest that the way management measures are executed may be at least as important as the fact that they are executed. No control group was available for this study because the intervention was applied at the national level. We therefore do not claim any causal relationships.

Exploring the validity and reliability of a questionnaire for evaluating virtual patient design with a special emphasis on fostering clinical reasoning

Background: Virtual patients (VPs) are increasingly used to train clinical reasoning. So far, no validated evaluation instruments for VP design are available. Aims: We examined the validity of an instrument for assessing the perception of VP design by learners. Methods: Three sources of validity evidence were examined: (i) Content was examined based on theory of clinical reasoning and an international VP expert team. (ii) The response process was explored in think-aloud pilot studies with medical students and in content analyses of free text questions accompanying each item of the instrument. (iii) Internal structure was assessed by exploratory factor analysis (EFA) and inter-rater reliability by generalizability analysis. Results: Content analysis was reasonably supported by the theoretical foundation and the VP expert team. The think-aloud studies and analysis of free text comments supported the validity of the instrument. In the EFA, using 2547 student evaluations of a total of 78 VPs, a three-factor model showed a reasonable fit with the data. At least 200 student responses are needed to obtain a reliable evaluation of a VP on all three factors. Conclusion: The instrument has the potential to provide valid information about VP design, provided that many responses per VP are available.

A clinical prediction model to identify patients at high risk of death in the emergency department.

PURPOSE Rapid assessment and intervention is important for the prognosis of acutely ill patients admitted to the emergency department (ED). The aim of this study was to prospectively develop and validate a model predicting the risk of in-hospital death based on all available information available at the time of ED admission and to compare its discriminative performance with a non-systematic risk estimate by the triaging first health-care provider. METHODS Prospective cohort analysis based on a multivariable logistic regression for the probability of death. RESULTS A total of 8,607 consecutive admissions of 7,680 patients admitted to the ED of a tertiary care hospital were analysed. Most frequent APACHE II diagnostic categories at the time of admission were neurological (2,052, 24 %), trauma (1,522, 18 %), infection categories [1,328, 15 %; including sepsis (357, 4.1 %), severe sepsis (249, 2.9 %), septic shock (27, 0.3 %)], cardiovascular (1,022, 12 %), gastrointestinal (848, 10 %) and respiratory (449, 5 %). The predictors of the final model were age, prolonged capillary refill time, blood pressure, mechanical ventilation, oxygen saturation index, Glasgow coma score and APACHE II diagnostic category. The model showed good discriminative ability, with an area under the receiver operating characteristic curve of 0.92 and good internal validity. The model performed significantly better than non-systematic triaging of the patient. CONCLUSIONS The use of the prediction model can facilitate the identification of ED patients with higher mortality risk. The model performs better than a non-systematic assessment and may facilitate more rapid identification and commencement of treatment of patients at risk of an unfavourable outcome.

Mycoplasma bovis infections in Swiss dairy cattle: a clinical investigation

Mycoplasma bovis causes mastitis in dairy cows and is associated with pneumonia and polyarthritis in cattle. The present investigation included a retrospective case–control study to identify potential herd-level risk factors for M. bovis associated disease, and a prospective cohort study to evaluate the course of clinical disease in M. bovis infected dairy cattle herds in Switzerland. Eighteen herds with confirmed M. bovis cases were visited twice within an average interval of 75 d. One control herd with no history of clinical mycoplasmosis, matched for herd size, was randomly selected within a 10 km range for each case herd. Animal health data, production data, information on milking and feeding-management, housing and presence of potential stress- factors were collected. Composite quarter milk samples were aseptically collected from all lactating cows and 5% of all animals within each herd were sampled by nasal swabs. Organ samples of culled diseased cows were collected when logistically possible. All samples were analyzed by real-time polymerase chain reaction (PCR). In case herds, incidence risk of pneumonia, arthritis and clinical mastitis prior to the first visit and incidence rates of clinical mastitis and clinical pneumonia between the two visits was estimated. Logistic regression was used to identify potential herd-level risk factors for M. bovis infection. In case herds, incidence risk of M. bovis mastitis prior to the first visit ranged from 2 to 15%, whereas 2 to 35% of the cows suffered from clinical pneumonia within the 12 months prior to the first herd visit. The incidence rates of mycoplasmal mastitis and clinical pneumonia between the two herd visits were low in case herds (0–0.1 per animal year at risk and 0.1-0.6 per animal year at risk, respectively). In the retrospective-case-control study high mean milk production, appropriate stimulation until milk-let-down, fore-stripping, animal movements (cattle shows and trade), presence of stress-factors, and use of a specific brand of milking equipment, were identified as potential herd-level risk factors. The prospective cohort study revealed a decreased incidence of clinical disease within three months and prolonged colonization of the nasal cavity by M. bovis in young stock.