Ageing reduces light touch and vibrotactile sensitivity on the anterior lower leg and foot dorsum.

Cutaneous mechanoreceptors in the anterior lower leg and foot dorsum provide important information about contact with objects and movement at the knee and ankle. This cutaneous feedback contributes to static and dynamic balance control. We conducted experiment 1 to determine the effects of ageing on anterior lower leg cutaneous feedback. We measured light touch (monofilament) perceptual thresholds (MPT) at seven skin sites across the anterior lower leg and foot dorsum in 12 young (5 male, aged 21-28) and 13 older adults (8 male, aged 73-92). Results showed that older adults had ~5.5× higher MPTs across these skin sites. We conducted experiment 2 to probe how different cutaneous mechanoreceptor subtypes are affected by ageing through measures of vibrotactile perceptual threshold (VPT) at 3, 15, and 40Hz at six skin sites across the anterior lower leg and foot dorsum in 10 young (5 male, aged 21-26) and 10 older adults (3 male, aged 75-85). In this group, we also assessed functional balance using the timed-up-and-go (TUG) and functional reach test (FRT). Older adults demonstrated significantly higher VPTs overall, and this effect was largest at 40Hz - a frequency primarily transmitted by fast adapting cutaneous afferents. Furthermore, higher thresholds at each frequency tended to correlate with poorer performance on the TUG within the older adult group (3Hz: r=0.550; 15Hz: r=0.689; 40Hz: r=0.663). These results suggest ageing influences cutaneous feedback from regions of the lower leg that provide important information about movement and contact.

Disparate metabolic response to fructose feeding between different mouse strains.

Diets enriched in fructose (FR) increase lipogenesis in the liver, leading to hepatic lipid accumulation and the development of insulin resistance. Previously, we have shown that in contrast to other mouse strains, BALB/c mice are resistant to high fat diet-induced metabolic deterioration, potentially due to a lack of ectopic lipid accumulation in the liver. In this study we have compared the metabolic response of BALB/c and C57BL/6 (BL6) mice to a fructose-enriched diet. Both strains of mice increased adiposity in response to FR-feeding, while only BL6 mice displayed elevated hepatic triglyceride (TAG) accumulation and glucose intolerance. The lack of hepatic TAG accumulation in BALB/c mice appeared to be linked to an altered balance between lipogenic and lipolytic pathways, while the protection from fructose-induced glucose intolerance in this strain was likely related to low levels of ER stress, a slight elevation in insulin levels and an altered profile of diacylglycerol species in the liver. Collectively these findings highlight the multifactorial nature of metabolic defects that develop in response to changes in the intake of specific nutrients and the divergent response of different mouse strains to dietary challenges.

Proprioceptively guided reaching movements in 3D space: effects of age, task complexity and handedness.

Aging is associated with impaired upper limb proprioceptive acuity, as reflected by decreased position matching accuracy with increasing task complexity and movement extent. Most studies have primarily used single-joint or planar paradigms to examine age-related changes in proprioception. It is unclear whether these changes can be generalized to more complex multi-joint movements, where additional sensory feedback may affect performance. Since age-related declines in cognitive function may impair the ability to integrate multiple sources of sensory feedback, deficits in position matching ability in older adults may persist when tasks are performed in three-dimensional space. The accuracy with which young and older participants reproduced remembered reference hand positions was assessed under different experimental conditions. Participants matched target locations located directly to the front or 45° to the side relative to the midline using the preferred and non-preferred arms. Either the same (i.e., ipsilateral matching) or the opposite (i.e., contralateral matching) arm was used to reproduce the target location. No differences in matching accuracy were found between young and older participants when matching ipsilaterally. When matching contralaterally, accuracy was worse in older participants for target locations located to the side, which may reflect age-related changes in the perception of peripersonal space. In contrast to previous studies, accuracy did not differ between the preferred and non-preferred arms in either group. These results extend previous findings demonstrating age-related impairments in proprioceptively guided arm movements when interhemispheric transfer is required.

Biomedical informatics: we are what we publish.

INTRODUCTION: This article is part of a For-Discussion-Section of Methods of Information in Medicine on "Biomedical Informatics: We are what we publish". It is introduced by an editorial and followed by a commentary paper with invited comments. In subsequent issues the discussion may continue through letters to the editor. OBJECTIVE: Informatics experts have attempted to define the field via consensus projects which has led to consensus statements by both AMIA. and by IMIA. We add to the output of this process the results of a study of the Pubmed publications with abstracts from the field of Biomedical Informatics. METHODS: We took the terms from the AMIA consensus document and the terms from the IMIA definitions of the field of Biomedical Informatics and combined them through human review to create the Health Informatics Ontology. We built a terminology server using the Intelligent Natural Language Processor (iNLP). Then we downloaded the entire set of articles in Medline identified by searching the literature by "Medical Informatics" OR "Bioinformatics". The articles were parsed by the joint AMIA / IMIA terminology and then again using SNOMED CT and for the Bioinformatics they were also parsed using HGNC Ontology. RESULTS: We identified 153,580 articles using "Medical Informatics" and 20,573 articles using "Bioinformatics". This resulted in 168,298 unique articles and an overlap of 5,855 articles. Of these 62,244 articles (37%) had titles and abstracts that contained at least one concept from the Health Informatics Ontology. SNOMED CT indexing showed that the field interacts with most all clinical fields of medicine. CONCLUSIONS: Further defining the field by what we publish can add value to the consensus driven processes that have been the mainstay of the efforts to date. Next steps should be to extract terms from the literature that are uncovered and create class hierarchies and relationships for this content. We should also examine the high occurring of MeSH terms as markers to define Biomedical Informatics. Greater understanding of the Biomedical Informatics Literature has the potential to lead to improved self-awareness for our field.

Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding.

AIMS/HYPOTHESIS: Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). METHODS: Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to measure markers of mitochondrial metabolism, inflammation, oxidative stress and lipid accumulation. RESULTS: BL6, 129X1, DBA/2 and FVB/N mice were all susceptible to varying degrees to HFD-induced obesity, glucose intolerance and insulin resistance, but BALB/c mice exhibited some protection from these detrimental effects. This protection could not be explained by differences in mitochondrial metabolism or oxidative stress in liver or muscle, or inflammation in adipose tissue. Interestingly, in contrast with the other strains, BALB/c mice did not accumulate excess lipid (triacylglycerols and diacylglycerols) in the liver; this is potentially related to lower fatty acid uptake rather than differences in lipogenesis or lipid oxidation. CONCLUSIONS/INTERPRETATION: Collectively, our findings indicate that most mouse strains develop metabolic defects on an HFD. However, there are inherent differences between strains, and thus the genetic background needs to be considered carefully in metabolic studies.

A review of medication reconciliation issues and experiences with clinical staff and information systems.

Medication reconciliation was developed to reduce medical mistakes and injuries through a process of creating and comparing a current medication list from independent patient information sources, and resolving discrepancies. The structure and clinician assignments of medication reconciliation varies between institutions, but usually includes physicians, nurses and pharmacists. The Joint Commission has recognized the value of medication reconciliation and mandated implementation in 2006; however, a variety of issues have prevented simple, easy, and universal implementation. This review references issues related to the development and the implementation of medication reconciliation including: - the need of a system or standard for accurate drug identification to create a definitive 'gold standard' patient medication list, - identifying stakeholders of medication reconciliation within the institution and contrasting staff interest and participation with institutional resources, - observations and opportunities of integrating medication reconciliation with the electronic patient health record, and - summarizing a series of institutions experiences developing and implementing medication reconciliation. Last, as medication reconciliation becomes a regular process within medical centers, key concepts for effective implementation are discussed.

Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle and narcoleptic episodes in Ox-/- mice.

BACKGROUND AND PURPOSE: Histamine H3 receptor antagonists are currently being evaluated in clinical trials for a number of central nervous system disorders including narcolepsy. These agents can increase wakefulness (W) in cats and rodents following acute administration, but their effects after repeat dosing have not been reported previously. EXPERIMENTAL APPROACH: EEG and EMG recordings were used to investigate the effects of acute and repeat administration of the novel H3 antagonist GSK189254 on the sleep-wake cycle in wild-type (Ox+/+) and orexin knockout (Ox-/-) mice, the latter being genetically susceptible to narcoleptic episodes. In addition, we investigated H3 and H1 receptor expression in this model using radioligand binding and autoradiography. KEY RESULTS: In Ox+/+ and Ox-/- mice, acute administration of GSK189254 (3 and 10 mg x kg(-1) p.o.) increased W and decreased slow wave and paradoxical sleep to a similar degree to modafinil (64 mg x kg(-1)), while it reduced narcoleptic episodes in Ox-/- mice. After twice daily dosing for 8 days, the effect of GSK189254 (10 mg x kg(-1)) on W in both Ox+/+ and Ox-/- mice was significantly reduced, while the effect on narcoleptic episodes in Ox-/- mice was significantly increased. Binding studies revealed no significant differences in H3 or H1 receptor expression between Ox+/+ and Ox-/- mice. CONCLUSIONS AND IMPLICATIONS: These studies provide further evidence to support the potential use of H3 antagonists in the treatment of narcolepsy and excessive daytime sleepiness. Moreover, the differential effects observed on W and narcoleptic episodes following repeat dosing could have important implications in clinical studies.

Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice.

BACKGROUND AND PURPOSE: Histamine H3 receptor antagonists are currently being evaluated for their potential use in a number of central nervous system disorders including Alzheimer's Disease (AD). To date, little is known about the state of H3 receptors in AD. EXPERIMENTAL APPROACH: In the present study we used the radiolabelled H3 receptor antagonist [3H]GSK189254 to investigate H3 receptor binding in the amyloid over-expressing double mutant APPswe x PSI.MI46V (TASTPM) transgenic mouse model of AD and in post-mortem human AD brain samples. KEY RESULTS: No significant differences in specific H3 receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [3H]GSK189254 binding was detected in sections of human medial frontal cortex from AD brains of varying disease severity (Braak stages I-VI). With more quantitative analysis in a larger cohort, we observed that H3 receptor densities were not significantly different between AD and age-matched control brains in both frontal and temporal cortical regions. However, within the AD group, [3H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death. CONCLUSIONS AND IMPLICATIONS: The maintenance of H3 receptor integrity observed in the various stages of AD in this study is important, given the potential use of H3 antagonists as a novel therapeutic approach for the symptomatic treatment of AD.

Less is more: high pass filtering, to remove up to 99% of the surface EMG signal power, improves EMG-based biceps brachii muscle force estimates.

It is generally assumed that raw surface EMG (sEMG) should be high pass filtered with cutoffs of 10-30 Hz to remove motion artifact before subsequent processing to estimate muscle force. The purpose of the current study was to explore the benefits of filtering out much of the raw sEMG signal when attempting to estimate accurate muscle forces. Twenty-five subjects were studied as they performed rapid static, anisotonic contractions of the biceps brachii. Biceps force was estimated (as a percentage of maximum) based on forces recorded at the wrist. An iterative approach was used to process the sEMG from the biceps brachii, using progressively greater high pass cutoff frequencies (20-440 Hz in steps of 30 Hz) with first and sixth order filters, as well as signal whitening, to determine the effects on the accuracy of EMG-based biceps force estimates. The results indicate that removing up to 99% of the raw sEMG signal power resulted in significant and substantial improvements in biceps force estimates. These findings challenge previous assumptions that the raw sEMG signal power between about 20 and 500 Hz should used when estimating muscle force. For the purposes of force prediction, it appears that a much smaller, high band of sEMG frequencies may be associated with force and the remainder of the spectrum has little relevance for force estimation.

The responses of leg and trunk muscles to sudden unloading of the hands: implications for balance and spine stability.

OBJECTIVE: To examine the anticipatory and responsive actions of leg and trunk muscles, and their role in whole-body and spine control in situations of sudden unloading of the hands in the sagittal plane. DESIGN: EMG and force plate measures were used to determine the baseline, anticipatory responses and post unloading responses of selected trunk and leg muscles under different conditions of unload timing knowledge. BACKGROUND: Postural muscles have been observed to increase activation in anticipation of a known loading situation to decrease the overall effect of an impulsive load delivered to the spine. It is thought that this increased activation places the spine in a more stable state, thereby reducing the likelihood of injury. Comparisons have not been made previously of the responses of postural muscles to unloading conditions where the certainty of unload timing is varied. METHODS: Eleven male subjects, holding a 6.8 kg load in the hands, were subjected to three different unloading conditions: (1) voluntary load drop; (2) known timing of load release; (3) unknown timing of load release. Anterior-posterior center of pressure data, as well as EMG activity on 8 right side muscles, were collected for 10 trials in each condition. RESULTS: Anterior-posterior center of pressure responses were significantly different (P<0.05) between each of the three conditions. Lumbar erector spinae and thoracic erector spinae significantly decreased anticipatory activity as knowledge of the unload timing increased. Five of the eight monitored muscles demonstrated significantly decreased response levels as knowledge of the timing of unloading increased. CONCLUSIONS: When an unload is self-triggered, preparatory adjustments can be made which reduce the overall postural perturbation to the body, and the spine in particular, while minimizing the responsive activity of trunk muscles. RELEVANCE: Spinal instability has been identified as a risk factor for low back injury during trunk loading. This study demonstrates that, in situations of sudden unloading, knowledge of the timing of the unloading may lead to anticipatory actions of postural muscles which actually decrease spinal stability, thereby increasing the risk of injury were an unexpected perturbation to occur.

Integrating pharmacokinetics knowledge into a drug ontology: as an extension to support pharmacogenomics.

The newly developed U.S. Common Medication Information Infrastructure was used as a basis to capture and formally express the properties of drugs relevant to research and the clinical application of pharmacogenomics. Two associated taxonomies within the model, Mechanism of Action and Physiologic Effect, were enriched to accommodate pharmacogenomic use-cases; the 4,000 active ingredients in the VA NDF-RT drug file were related to the enhanced taxonomies. Pharmacokinetics were independently modeled for pharmacogenomics and tested against thirty-one high-profile drugs to demonstrate our approach.

Automated enhancement of description logic-defined terminologies to facilitate mapping to ICD9-CM.

Compositional (post-coordinated) terminologies are one potential solution to the problem of content completeness. However, they have the potential to render data incomparable. For computers to determine that compositional expressions are comparable, the relations between the composed components that are understood implicitly by human readers must be represented explicitly for computer manipulation. We discuss a technique for discovering and formalizing the implicit semantic relationships in two vocabularies: the International Classification of Disease Version 9 Clinical Modification (ICD9-CM), and SNOMED-Reference Terminology (SNOMED-RT). The results of this technique are used to augment the existing SNOMED-RT relation ontology, which is a necessary step in automated concept mapping between systems. The reference terminology must contain all the semantics implicit in the classification in order to map concepts between the two representations. We also provide an explicit representation of the implied semantics of ICD9-CM. This tabulation will be useful for other knowledge engineering efforts involving ICD9-CM.

Guideline for health informatics: controlled health vocabularies--vocabulary structure and high-level indicators.

Developers and purchasers of controlled health terminologies require valid mechanisms for comparing terminological systems. By Controlled Health Vocabularies we refer to terminologies and terminological systems designed to represent clinical data at a granularity consistent with the practice of today's healthcare delivery. Comprehensive criterion for the evaluation of such systems are lacking and the known criteria are inconsistently applied. Although there are many papers, which describe specific desirable features of a controlled health vocabulary, to date there is not a consistent guide for evaluators of terminologies to reference, which will help them compare implementations of terminological systems on an equal footing 1,2 This guideline serves to fill the gap between academic enumeration of desirable terminological characteristics and the practical implementation or rigorous evaluations which will yield comparable data regarding the quality of one or more controlled health vocabularies.

Development of a homogeneous MAP kinase reporter gene screen for the identification of agonists and antagonists at the CXCR1 chemokine receptor.

Agonist activity at G protein-coupled receptors (GPCRs) that regulate heterotrimeric G proteins of the Galpha(i/o) or Galpha(q) families has been shown to result in activation of the mitogen-activated protein (MAP) kinase cascade. To facilitate compound screening for these classes of GPCR, we have developed a reporter gene that detects the activation of the ternary complex transcription factor Sap1a following MAP kinase activation. In contrast to other reporter gene assays for Galpha(i/o)-coupled GPCRs, the MAP kinase reporter generates an increase in signal in the presence of agonist. The reporter gene has been transfected into Chinese hamster ovary cells to generate a "host" reporter gene-containing cell line. The Galpha(i)-coupled human CXCR1 chemokine receptor was subsequently transfected into this cell line in order to develop a 384-well format screen for both agonists and antagonists of this receptor. Agonists activated the reporter gene with the expected rank order of potency and with similar concentration dependence as seen with the regulation of other signal transduction cascades in mammalian cells: interleukin-8 (IL-8) (pEC(50) = 7.0 +/- 0.1) > GCP-2 (pEC(50) = 6.3 +/- 0.1) > NAP-2 (pEC(50) < 6). CXCR1-mediated activation of MAP kinase was inhibited by pertussis toxin and the MEK inhibitor PD98059, demonstrating that receptor activation of MAP kinase is due to pertussis toxin-sensitive Galpha(i/o)-family G proteins to cause the activation of MEK kinase. Using the 384-well format, assay performance was unaffected by solvent concentrations of 0.5% ethanol, 0.15% glycerol, or 1% DMSO. Signal crosstalk between adjacent wells was less than 1%. The assay exhibited a Z factor of 0.53 and a coefficient of variation of response to repeated application of IL-8 (100 nM) of 15.9%.

Derivation and evaluation of a document-naming nomenclature.

OBJECTIVE: The Computerized Patient Record System is deployed at all 173 Veterans Affairs (VA) medical centers. Providers access clinical notes in the system from a note title menu. Following its implementation at the Nashville VA Medical Center, users expressed dissatisfaction with the time required find notes among hundreds of irregularly structured titles. The authors' objective was to develop a document-naming nomenclature (DNN) that creates informative, structured note titles that improve information access. DESIGN: One thousand ninety-four unique note titles from two VA medical centers were reviewed. A note-naming nomenclature and compositional syntax were derived. Compositional order was determined by user preference survey. MEASUREMENTS: The DNN was evaluated by modeling note titles from the Salt Lake City VA Medical Center (n=877), Vanderbilt University Medical Center (n=554), and the Mayo Clinic (n=42). A preliminary usability evaluation was conducted on a structured title display and sorting application. RESULTS: Classes of note title components were found by inspection. Components describe characteristics of the author, the health care event, and the organizational unit providing care. Terms were taken from VA medical center information systems and national standards. The DNN model accurately described 97 to 99 percent of note titles from the test sites. The DNN term coverage varied, depending on component and site. Users found the DNN title format useful and the DNN-based title sorting and note review application easy to learn and quick to use. CONCLUSION: The DNN accurately models note titles at five medical centers. Preliminary usability data indicate that DNN integration with title parsing and sorting software enhances information access.

Humicola insolens cellobiose dehydrogenase: cloning, redox chemistry, and "logic gate"-like dual functionality.

1Cellobiose dehydrogenase is a hemoflavoenzyme that catalyzes the sequential electron-transfer from an electron-donating substrate (e.g. cellobiose) to a flavin center, then to an electron-accepting substrate (e.g. quinone) either directly or via a heme center after an internal electron-transfer from the flavin to heme. We cloned the dehydrogenase from Humicola insolens, which encodes a protein of 761 amino acid residues containing an N-terminal heme domain and a C-terminal flavin domain, and studied how the catalyzed electron transfers are regulated. Based on the correlation between the rate and redox potential, we demonstrated that with a reduced flavin center, the enzyme, as a reductase, could export electron from its heme center by a "outer-sphere" mechanism. With the "resting" flavin center, however, the enzyme could have a peroxidase-like function and import electron to its heme center after a peroxidative activation. The dual functionality of its heme center makes the enzyme a molecular "logic gate", in which the electron flow through the heme center can be switched in direction by the redox state of the coupled flavin center.

A novel carbohydrate:acceptor oxidoreductase from Microdochium nivale.

A Microdochium nivale carbohydrate:acceptor oxidoreductase was purified, cloned, heterologously expressed, and characterized. The gene encoding the protein showed one intron, and the ORF showed a sequence with low homology (< or = 25% identity or 65% similarity) to other known flavin-containing carbohydrate oxidases. The maturation of the protein required the cleavage of a tetrameric propeptide in addition to an 18 amino-acid signal peptide. The enzyme was found to have a relative molecular mass of 55 000 Da, an isoelectric point of 9, and one FAD per protein. It could oxidize mono-, oligo-, or polymeric saccharides, and transfer their electrons to O2 or other acceptors. When D-glucose served as electron-donating substrate, an activity of 2 s(-1) was observed at pH 5.5 and 23 degrees C. Among various oligosaccharides, the enzyme preferred tetrameric dextrins, indicating a favorable interaction of four linked glucose units with the substrate pocket. The unique structure and ability of oxidizing oligo/polymeric saccharides suggest a promising prospect of this enzyme for various industrial/medicinal applications.

Usability evaluation of the progress note construction set.

OVERVIEW: The Veterans Administration (VA) Computerized Patient Record System (CPRS) is a nationally deployed software product that integrates provider order entry, progress notes, vitals, consults, discharge summaries, problem lists, medications, labs, radiology, transcribed documents, study reports, and clinical reminders. Users rapidly adopted the graphical user interface for data retrieval, but demanded options to typing for data entry. We programmed "point and click" forms that integrate with CPRS individually, but were soon overwhelmed by requests. Subsequently, we developed the Progress Note Construction Set (PNCS); a tool suite that permits subject matter experts without programming skills to create reusable "point and click" forms. In this study, we evaluate the usability of these user-constructed forms. METHODS: An untrained, non-VA subject matter expert used the PNCS to create a graphical form for "skin tear" documentation. Ten VA nurses used the skin tear form to document findings for 7 standardized clinical scenarios. Following each scenario the subjects answered usability questions about the form. RESULTS: The subject matter expert created the skin tear form in 78 minutes. Users found the form to facilitate their data entry (p 0.0265), and to be at least as fast (p 0.0029) and as easy to use as expected (p 0.0166). Average note entry time was 3.4 minutes. CONCLUSION: The PNCS allowed a non-programmer to quickly create a usable, CPRS-integrated point and click form. Users found the subject matter expert s form fast and easy to use. The tool suite is a more scaleable form creation method because capacity is no longer limited by programmer availability.

A randomized controlled trial of the accuracy of clinical record retrieval using SNOMED-RT as compared with ICD9-CM.

BACKGROUND: Concept-based Indexing is purported to provide more granular data representation for clinical records.1,2 This implies that a detailed clinical terminology should be able to provide improved access to clinical records. To date there is no data to show that a clinical reference terminology is superior to a precoordinated terminology in its ability to provide access to the clinical record. Today, ICD9-CM is the most commonly used method of retrieving clinical records. OBJECTIVE: In this study, we compare the sensitivity, specificity, positive likelihood ratio, positive predictive value and accuracy of SNOMED-RT vs. ICD9-CM in retrieving ten diagnoses from a random sample of 2,022 episodes of care. METHOD: We randomly selected 1,014 episodes of care from the inpatient setting and 1,008 episodes of care from the outpatient setting. Each record had associated with it, the free text final diagnoses from the Master Sheet Index at the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the episode of care. The free text diagnoses were coded by two expert indexers (disagreements were addressed by a Staff Clinician) as to whether queries regarding one of 5 common or 5 uncommon diagnoses should return this encounter. The free text entries were automatically coded using the Mayo Vocabulary Processor. Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM and using these entry points, a retrieval set was generated from the underlying corpus of records. Each retrieval set was compared with the Gold Standard created by the expert indexers. RESULTS: SNOMED-RT produced significantly greater specificity in its retrieval sets (99.8% vs. 98.3%, p<0.001 McNemar Test). The positive likelihood ratios were significantly better for SNOMED-RT retrieval sets (264.9 vs. 33.8, p<0.001 McNemar Test). The positive predictive value of a SNOMED-RT retrieval was also significantly better than ICD9-CM (92.9% vs. 62.4%, p<0.001 McNemar Test). The accuracy defined as 1 (the total error rate (FP+FN) / Total # episodes queried (20,220)) was significantly greater for SNOMED-RT (98.2% vs. 96.8%, p=0.002 McNemar Test). Interestingly, the sensitivity of the SNOMED-RT generated retrieval set was not significantly different from ICD9-CM, but there was a trend toward significance (60.4% vs. 57.6%, p=0.067 McNemar Test). However, if we examine only the outpatient practice SNOMED-RT produced a more sensitive retrieval set than ICD9-CM (54.8% vs. 46.4%, p=0.002 McNemar Test). CONCLUSIONS: Our data clearly shows that information regarding both common and rare disorders is more accurately identified with automated SNOMED-RT indexing using the Mayo Vocabulary Processor than it is with traditional hand picked constellations of codes using ICD9-CM. SNOMED-RT provided more sensitive retrievals of outpatient episodes of care than ICD9-CM.

Motor control testing of upper limb function after botulinum toxin injection: a case study.

OBJECTIVE: To evaluate changes in upper extremity function in a hemiparetic patient after treatment with botulinum toxin (BTX) using motor-control testing (MCT) techniques. DESIGN: Interventional with longitudinal study, open label. SETTING: A children's hospital and a motor-control laboratory at a major academic center. PARTICIPANTS: A 16-year-old male with right hemiparetic cerebral palsy and a healthy 12-year-old control subject. INTERVENTIONS: BTX injections to the elbow and wrist flexors. MAIN OUTCOME MEASURES: MCT was used to examine 4 upper extremity movements: forward reach, bilateral rhythmic movements (both muscle homologous and direction homologous), isometric pinch, and hand tapping. The patient was tested before treatment and at 2, 4, 6, 12, 18, and 24 weeks after treatment. In addition, range of motion (ROM), the Ashworth scale of spasticity, Functional Independence Measure, and the mobility and activities of daily living (ADL) sections of the Pediatric Evaluation of the Disability Inventory were performed. RESULTS: Forward reach demonstrated little change initially despite patient reports of "feeling looser." Improvement was noted after 18 weeks, but returned to baseline level at 24 weeks. Bilateral rhythmic movements also showed slight improvement at 18 weeks. Pinch force increased significantly after 2 weeks, but declined again at 6 weeks. Improvements occurred in ROM and the Ashworth rating of spasticity, but were not temporally associated with each other or with MCT results. Functional assessment data did not change during the study period. CONCLUSIONS: Improvements in more complex motor tasks were noted after significant delay from the time of treatment, while simpler tasks demonstrated a more rapid improvement, followed by a rapid return to baseline levels. This case suggests that MCT techniques can provide quantitative and qualitative data, which can add new information about upper extremity motor disability and the outcome of treatment.