Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Nutritional management of children with cerebral palsy: a practical guide

Peer reviewedFinal Published versio

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Embodied perspective-taking indicated by selective disruption from aberrant self motion

Spatial perspective-taking that involves imagined changes in one’s spatial orientation is facilitated by vestibular stimulation inducing a congruent sensation of self-motion. We examined further the role of vestibular resources in perspective-taking by evaluating whether aberrant and conflicting vestibular stimulation impaired perspective-taking performance. Participants (N = 39) undertook either an “own body transformation” (OBT)task, requiring speeded spatial judgments made from the perspective of a schematic figure, or a control task requiring reconfiguration of spatial mappings from one’s own visuo-spatial perspective. These tasks were performed both without and with vestibular stimulation by whole-body Coriolis motion, according to a repeated measures design, balanced for order. Vestibular stimulation was found to impair performance during the first minute post stimulus relative to the stationary condition. This disruption was task-specific, affecting only the OBT task and not the control task, and dissipated by the second minute post-stimulus. Our experiment thus demonstrates selective temporary impairment of perspective-taking from aberrant vestibular stimulation, implying that uncompromised vestibular resources are necessary for efficient perspective-taking. This finding provides evidence for an embodied mechanism for perspective-taking whereby vestibular input contributes to multisensory processing underlying bodily and social cognition. Ultimately, this knowledge may contribute to the design of interventions that help patients suffering sudden vertigo adapt to the cognitive difficulties caused by aberrant vestibular stimulation

A diagnosis of the plasma waves responsible for the explosive energy release of substorm onset

During geomagnetic substorms, stored magnetic and plasma thermal energies are explosively converted into plasma kinetic energy. This rapid reconfiguration of Earth’s nightside magnetosphere is manifest in the ionosphere as an auroral display that fills the sky. Progress in understanding of how substorms are initiated is hindered by a lack of quantitative analysis of the single consistent feature of onset; the rapid brightening and structuring of the most equatorward arc in the ionosphere. Here, we exploit state-of-the-art auroral measurements to construct an observational dispersion relation of waves during substorm onset. Further, we use kinetic theory of high-beta plasma to demonstrate that the shear Alfven wave dispersion relation bears remarkable similarity to the auroral dispersion relation. In contrast to prevailing theories of substorm initiation, we demonstrate that auroral beads seen during the majority of substorm onsets are likely the signature of kinetic Alfven waves driven unstable in the high-beta magnetotail

Formation of Sclerotia and Production of Indoloterpenes by Aspergillus niger and Other Species in Section Nigri

Several species in Aspergillus section Nigri have been reported to produce sclerotia on well-known growth media, such as Czapek yeast autolysate (CYA) agar, with sclerotia considered to be an important prerequisite for sexual development. However Aspergillus niger sensu stricto has not been reported to produce sclerotia, and is thought to be a purely asexual organism. Here we report, for the first time, the production of sclerotia by certain strains of Aspergillus niger when grown on CYA agar with raisins, or on other fruits or on rice. Up to 11 apolar indoloterpenes of the aflavinine type were detected by liquid chromatography and diode array and mass spectrometric detection where sclerotia were formed, including 10,23-dihydro-24,25-dehydroaflavinine. Sclerotium induction can thus be a way of inducing the production of new secondary metabolites from previously silent gene clusters. Cultivation of other species of the black aspergilli showed that raisins induced sclerotium formation by A. brasiliensis, A. floridensis A. ibericus, A. luchuensis, A. neoniger, A. trinidadensis and A. saccharolyticus for the first time

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Scaled momentum distributions for K-S(0) and Λ /̄ Λ in DIS at HERA

Scaled momentum distributions for the strange hadrons K0S and Λ/Λ¯ were measured in deep inelastic ep scattering with the ZEUS detector at HERA using an integrated luminosity of 330 pb−1. The evolution of these distributions with the photon virtuality, Q 2, was studied in the kinematic region 10 < Q 2  < 40000 GeV2 and 0.001 < x < 0.75, where x is the Bjorken scaling variable. Clear scaling violations are observed. Predictions based on different approaches to fragmentation were compared to the measurements. Leading-logarithm parton-shower Monte Carlo calculations interfaced to the Lund string fragmentation model describe the data reasonably well in the whole range measured. Next-to-leading-order QCD calculations based on fragmentation functions, FFs, extracted from e + e − data alone, fail to describe the measurements. The calculations based on FFs extracted from a global analysis including e + e −, ep and pp data give an improved description. The measurements presented in this paper have the potential to further constrain the FFs of quarks, anti-quarks and gluons yielding K0S and Λ/Λ¯ strange hadrons

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag−/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.National Institutes of Health (U.S.) (NIH grant R01-CA075576)National Institutes of Health (U.S.) (NIH grant R01-CA055042)National Institutes of Health (U.S.) (NIH grant R01-CA149261)National Institutes of Health (U.S.) (NIH grant P30-ES00002)National Institutes of Health (U.S.) (NIH grant P30-ES02109)National Center for Research Resources (U.S.) (grant number M01RR-01066)National Center for Research Resources (U.S.) (grant number UL1 RR025758, Harvard Clinical and Translational Science Center

Atypical Neurophysiology Underlying Episodic and Semantic Memory in Adults with Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) show atypicalities in episodic memory (Boucher et al. in Psychological Bulletin, 138 (3), 458-496, 2012). We asked participants to recall the colours of a set of studied line drawings (episodic judgement), or to recognize line drawings alone (semantic judgement). Cycowicz et al. (Journal of Experimental Child Psychology, 65, 171-237, 2001) found early (300 ms onset) posterior old-new event-related potential effects for semantic judgements in typically developing (TD) individuals, and occipitally focused negativity (800 ms onset) for episodic judgements. Our results replicated findings in TD individuals and demonstrate attenuated early old-new effects in ASD. Late posterior negativity was present in the ASD group, but was not specific to this time window. This non-specificity may contribute to the atypical episodic memory judgements characteristic of individuals with ASD