Sample records for accumulating clinical evidence

  1. Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.

    PubMed

    Cherepanoff, Svetlana; Killingsworth, Murray C; Zhu, Meidong; Nolan, Timothy; Hunyor, Alex P; Young, Stephanie H; Hageman, Gregory S; Gillies, Mark C

    2012-11-01

    To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.

  2. Sequential biases in accumulating evidence

    PubMed Central

    Huggins, Richard; Dogo, Samson Henry

    2015-01-01

    Whilst it is common in clinical trials to use the results of tests at one phase to decide whether to continue to the next phase and to subsequently design the next phase, we show that this can lead to biased results in evidence synthesis. Two new kinds of bias associated with accumulating evidence, termed ‘sequential decision bias’ and ‘sequential design bias’, are identified. Both kinds of bias are the result of making decisions on the usefulness of a new study, or its design, based on the previous studies. Sequential decision bias is determined by the correlation between the value of the current estimated effect and the probability of conducting an additional study. Sequential design bias arises from using the estimated value instead of the clinically relevant value of an effect in sample size calculations. We considered both the fixed‐effect and the random‐effects models of meta‐analysis and demonstrated analytically and by simulations that in both settings the problems due to sequential biases are apparent. According to our simulations, the sequential biases increase with increased heterogeneity. Minimisation of sequential biases arises as a new and important research area necessary for successful evidence‐based approaches to the development of science. © 2015 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd. PMID:26626562

  3. [Genetic Mutation Accumulation and Clinical Outcome of Immune Checkpoint Blockade Therapy].

    PubMed

    Takahashi, Masanobu

    2016-06-01

    Immune checkpoint blockade therapy has recently attracted great attention in the area of oncology. In Japan, since 2014, an anti-PD-1 antibody nivolumab and anti-CTLA-4 antibody ipilimumab have been available for the treatment of patients with malignant melanoma, and nivolumab has been available for patients with non-small cell lung cancer. Clinical trials using these drugs and other immune checkpoint inhibitors are currently in progress worldwide. The immune checkpoint blockade therapy is a promising new cancer therapy; however, not all patients with cancer can benefit from this therapy. Recent evidence shows that markers reflecting the extent of genetic mutation accumulation, including mutation burden, non-synonymous mutation that produces neoantigen, and microsatellite instability, possibly serve as promising marker to predict who can benefit from the immune checkpoint blockade therapy. Here, I introduce the recent evidence and discuss the correlation between genetic mutation accumulation and clinical outcome of immune checkpoint blockade therapy.

  4. Discriminating evidence accumulation from urgency signals in speeded decision making.

    PubMed

    Hawkins, Guy E; Wagenmakers, Eric-Jan; Ratcliff, Roger; Brown, Scott D

    2015-07-01

    The dominant theoretical paradigm in explaining decision making throughout both neuroscience and cognitive science is known as “evidence accumulation”--The core idea being that decisions are reached by a gradual accumulation of noisy information. Although this notion has been supported by hundreds of experiments over decades of study, a recent theory proposes that the fundamental assumption of evidence accumulation requires revision. The "urgency gating" model assumes decisions are made without accumulating evidence, using only moment-by-moment information. Under this assumption, the successful history of evidence accumulation models is explained by asserting that the two models are mathematically identical in standard experimental procedures. We demonstrate that this proof of equivalence is incorrect, and that the models are not identical, even when both models are augmented with realistic extra assumptions. We also demonstrate that the two models can be perfectly distinguished in realistic simulated experimental designs, and in two real data sets; the evidence accumulation model provided the best account for one data set, and the urgency gating model for the other. A positive outcome is that the opposing modeling approaches can be fruitfully investigated without wholesale change to the standard experimental paradigms. We conclude that future research must establish whether the urgency gating model enjoys the same empirical support in the standard experimental paradigms that evidence accumulation models have gathered over decades of study. Copyright © 2015 the American Physiological Society.

  5. Evidence accumulation as a model for lexical selection.

    PubMed

    Anders, R; Riès, S; van Maanen, L; Alario, F X

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Evidence accumulation detected in BOLD signal using slow perceptual decision making.

    PubMed

    Krueger, Paul M; van Vugt, Marieke K; Simen, Patrick; Nystrom, Leigh; Holmes, Philip; Cohen, Jonathan D

    2017-04-01

    We assessed whether evidence accumulation could be observed in the BOLD signal during perceptual decision making. This presents a challenge since the hemodynamic response is slow, while perceptual decisions are typically fast. Guided by theoretical predictions of the drift diffusion model, we slowed down decisions by penalizing participants for incorrect responses. Second, we distinguished BOLD activity related to stimulus detection (modeled using a boxcar) from activity related to integration (modeled using a ramp) by minimizing the collinearity of GLM regressors. This was achieved by dissecting a boxcar into its two most orthogonal components: an "up-ramp" and a "down-ramp." Third, we used a control condition in which stimuli and responses were similar to the experimental condition, but that did not engage evidence accumulation of the stimuli. The results revealed an absence of areas in parietal cortex that have been proposed to drive perceptual decision making but have recently come into question; and newly identified regions that are candidates for involvement in evidence accumulation. Previous fMRI studies have either used fast perceptual decision making, which precludes the measurement of evidence accumulation, or slowed down responses by gradually revealing stimuli. The latter approach confounds perceptual detection with evidence accumulation because accumulation is constrained by perceptual input. We slowed down the decision making process itself while leaving perceptual information intact. This provided a more sensitive and selective observation of brain regions associated with the evidence accumulation processes underlying perceptual decision making than previous methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Evidence Accumulator or Decision Threshold – Which Cortical Mechanism are We Observing?

    PubMed Central

    Simen, Patrick

    2012-01-01

    Most psychological models of perceptual decision making are of the accumulation-to-threshold variety. The neural basis of accumulation in parietal and prefrontal cortex is therefore a topic of great interest in neuroscience. In contrast, threshold mechanisms have received less attention, and their neural basis has usually been sought in subcortical structures. Here I analyze a model of a decision threshold that can be implemented in the same cortical areas as evidence accumulators, and whose behavior bears on two open questions in decision neuroscience: (1) When ramping activity is observed in a brain region during decision making, does it reflect evidence accumulation? (2) Are changes in speed-accuracy tradeoffs and response biases more likely to be achieved by changes in thresholds, or in accumulation rates and starting points? The analysis suggests that task-modulated ramping activity, by itself, is weak evidence that a brain area mediates evidence accumulation as opposed to threshold readout; and that signs of modulated accumulation are as likely to indicate threshold adaptation as adaptation of starting points and accumulation rates. These conclusions imply that how thresholds are modeled can dramatically impact accumulator-based interpretations of this data. PMID:22737136

  8. Normative evidence accumulation in unpredictable environments

    PubMed Central

    Glaze, Christopher M; Kable, Joseph W; Gold, Joshua I

    2015-01-01

    In our dynamic world, decisions about noisy stimuli can require temporal accumulation of evidence to identify steady signals, differentiation to detect unpredictable changes in those signals, or both. Normative models can account for learning in these environments but have not yet been applied to faster decision processes. We present a novel, normative formulation of adaptive learning models that forms decisions by acting as a leaky accumulator with non-absorbing bounds. These dynamics, derived for both discrete and continuous cases, depend on the expected rate of change of the statistics of the evidence and balance signal identification and change detection. We found that, for two different tasks, human subjects learned these expectations, albeit imperfectly, then used them to make decisions in accordance with the normative model. The results represent a unified, empirically supported account of decision-making in unpredictable environments that provides new insights into the expectation-driven dynamics of the underlying neural signals. DOI: http://dx.doi.org/10.7554/eLife.08825.001 PMID:26322383

  9. Conscious and Nonconscious Processes:Distinct Forms of Evidence Accumulation?

    NASA Astrophysics Data System (ADS)

    Dehaene, Stanislas

    Among the many brain events evoked by a visual stimulus, which ones are associated specifically with conscious perception, and which merely reflect nonconscious processing? Understanding the neuronal mechanisms of consciousness is a major challenge for cognitive neuroscience. Recently, progress has been achieved by contrasting behavior and brain activation in minimally different experimental conditions, one of which leads to conscious perception whereas the other does not. This chapter reviews briefly this line of research and speculates on its theoretical interpretation. I propose to draw links between evidence accumulation models, which are highly successful in capturing elementary psychophysical decisions, and the conscious/nonconscious dichotomy. In this framework, conscious access would correspond to the crossing of a threshold in evidence accumulation within a distributed global workspace, a set of recurrently connected neurons with long axons that is able to integrate and broadcast back evidence from multiple brain processors. During nonconscious processing, evidence would be accumulated locally within specialized subcircuits, but would fail to reach the threshold needed for global ignition and, therefore, conscious reportability.

  10. Accumulation of evidence during sequential decision making: the importance of top-down factors.

    PubMed

    de Lange, Floris P; Jensen, Ole; Dehaene, Stanislas

    2010-01-13

    In the last decade, great progress has been made in characterizing the accumulation of neural information during simple unitary perceptual decisions. However, much less is known about how sequentially presented evidence is integrated over time for successful decision making. The aim of this study was to study the mechanisms of sequential decision making in humans. In a magnetoencephalography (MEG) study, we presented healthy volunteers with sequences of centrally presented arrows. Sequence length varied between one and five arrows, and the accumulated directions of the arrows informed the subject about which hand to use for a button press at the end of the sequence (e.g., LRLRR should result in a right-hand press). Mathematical modeling suggested that nonlinear accumulation was the rational strategy for performing this task in the presence of no or little noise, whereas quasilinear accumulation was optimal in the presence of substantial noise. MEG recordings showed a correlate of evidence integration over parietal and central cortex that was inversely related to the amount of accumulated evidence (i.e., when more evidence was accumulated, neural activity for new stimuli was attenuated). This modulation of activity likely reflects a top-down influence on sensory processing, effectively constraining the influence of sensory information on the decision variable over time. The results indicate that, when making decisions on the basis of sequential information, the human nervous system integrates evidence in a nonlinear manner, using the amount of previously accumulated information to constrain the accumulation of additional evidence.

  11. Evidence Accumulation and Choice Maintenance Are Dissociated in Human Perceptual Decision Making

    PubMed Central

    Pedersen, Mads Lund; Endestad, Tor; Biele, Guido

    2015-01-01

    Perceptual decision making in monkeys relies on decision neurons, which accumulate evidence and maintain choices until a response is given. In humans, several brain regions have been proposed to accumulate evidence, but it is unknown if these regions also maintain choices. To test if accumulator regions in humans also maintain decisions we compared delayed and self-paced responses during a face/house discrimination decision making task. Computational modeling and fMRI results revealed dissociated processes of evidence accumulation and decision maintenance, with potential accumulator activations found in the dorsomedial prefrontal cortex, right inferior frontal gyrus and bilateral insula. Potential maintenance activation spanned the frontal pole, temporal gyri, precuneus and the lateral occipital and frontal orbital cortices. Results of a quantitative reverse inference meta-analysis performed to differentiate the functions associated with the identified regions did not narrow down potential accumulation regions, but suggested that response-maintenance might rely on a verbalization of the response. PMID:26510176

  12. Four-hour quantitative real-time polymerase chain reaction-based comprehensive chromosome screening and accumulating evidence of accuracy, safety, predictive value, and clinical efficacy.

    PubMed

    Treff, Nathan R; Scott, Richard T

    2013-03-15

    Embryonic comprehensive chromosomal euploidy may represent a powerful biomarker to improve the success of IVF. However, there are a number of aneuploidy screening strategies to consider, including different technologic platforms with which to interrogate the embryonic DNA, and different embryonic developmental stages from which DNA can be analyzed. Although there are advantages and disadvantages associated with each strategy, a series of experiments producing evidence of accuracy, safety, clinical predictive value, and clinical efficacy indicate that trophectoderm biopsy and quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) may represent a useful strategy to improve the success of IVF. This Biomarkers in Reproductive Medicine special issue review summarizes the accumulated experience with the development and clinical application of a 4-hour blastocyst qPCR-based CCS technology. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Active inference, evidence accumulation and the urn task

    PubMed Central

    FitzGerald, Thomas HB; Schwartenbeck, Philipp; Moutoussis, Michael; Dolan, Raymond J; Friston, Karl

    2015-01-01

    Deciding how much evidence to accumulate before making a decision is a problem we and other animals often face, but one which is not completely understood. This issue is particularly important because a tendency to sample less information (often known as reflection impulsivity) is a feature in several psychopathologies, such as psychosis. A formal understanding information sampling may therefore clarify the computational anatomy of psychopathology. In this theoretical paper, we consider evidence accumulation in terms of active (Bayesian) inference using a generic model of Markov decision processes. Here, agents are equipped with beliefs about their own behaviour – in this case, that they will make informed decisions. Normative decision-making is then modelled using variational Bayes to minimise surprise about choice outcomes. Under this scheme, different facets of belief updating map naturally onto the functional anatomy of the brain (at least at a heuristic level). Of particular interest is the key role played by the expected precision of beliefs about control, which we have previously suggested may be encoded by dopaminergic neurons in the midbrain. We show that manipulating expected precision strongly affects how much information an agent characteristically samples, and thus provides a possible link between impulsivity and dopaminergic dysfunction. Our study therefore represents a step towards understanding evidence accumulation in terms of neurobiologically plausible Bayesian inference, and may cast light on why this process is disordered in psychopathology. PMID:25514108

  14. Content-specific evidence accumulation in inferior temporal cortex during perceptual decision-making

    PubMed Central

    Tremel, Joshua J.; Wheeler, Mark E.

    2015-01-01

    During a perceptual decision, neuronal activity can change as a function of time-integrated evidence. Such neurons may serve as decision variables, signaling a choice when activity reaches a boundary. Because the signals occur on a millisecond timescale, translating to human decision-making using functional neuroimaging has been challenging. Previous neuroimaging work in humans has identified patterns of neural activity consistent with an accumulation account. However, the degree to which the accumulating neuroimaging signals reflect specific sources of perceptual evidence is unknown. Using an extended face/house discrimination task in conjunction with cognitive modeling, we tested whether accumulation signals, as measured using functional magnetic resonance imaging (fMRI), are stimulus-specific. Accumulation signals were defined as a change in the slope of the rising edge of activation corresponding with response time (RT), with higher slopes associated with faster RTs. Consistent with an accumulation account, fMRI activity in face- and house-selective regions in the inferior temporal cortex increased at a rate proportional to decision time in favor of the preferred stimulus. This finding indicates that stimulus-specific regions perform an evidence integrative function during goal-directed behavior and that different sources of evidence accumulate separately. We also assessed the decision-related function of other regions throughout the brain and found that several regions were consistent with classifications from prior work, suggesting a degree of domain generality in decision processing. Taken together, these results provide support for an integration-to-boundary decision mechanism and highlight possible roles of both domain-specific and domain-general regions in decision evidence evaluation. PMID:25562821

  15. Distinct effects of prefrontal and parietal cortex inactivations on an accumulation of evidence task in the rat

    PubMed Central

    Erlich, Jeffrey C; Brunton, Bingni W; Duan, Chunyu A; Hanks, Timothy D; Brody, Carlos D

    2015-01-01

    Numerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making, but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined. Here, in rats performing an auditory evidence accumulation task, we inactivated the frontal orienting fields (FOF) and posterior parietal cortex (PPC), two rat cortical regions that have neural correlates of accumulating evidence and that have been proposed as central to decision-making. We used a detailed model of the decision process to analyze the effect of inactivations. Inactivation of the FOF induced substantial performance impairments that were quantitatively best described as an impairment in the output pathway of an evidence accumulator with a long integration time constant (>240 ms). In contrast, we found a minimal role for PPC in decisions guided by accumulating auditory evidence, even while finding a strong role for PPC in internally-guided decisions. DOI: http://dx.doi.org/10.7554/eLife.05457.001 PMID:25869470

  16. Perception as Evidence Accumulation and Bayesian Inference: Insights from Masked Priming

    ERIC Educational Resources Information Center

    Norris, Dennis; Kinoshita, Sachiko

    2008-01-01

    The authors argue that perception is Bayesian inference based on accumulation of noisy evidence and that, in masked priming, the perceptual system is tricked into treating the prime and the target as a single object. Of the 2 algorithms considered for formalizing how the evidence sampled from a prime and target is combined, only 1 was shown to be…

  17. Evidence accumulation in obsessive-compulsive disorder: the role of uncertainty and monetary reward on perceptual decision-making thresholds.

    PubMed

    Banca, Paula; Vestergaard, Martin D; Rankov, Vladan; Baek, Kwangyeol; Mitchell, Simon; Lapa, Tatyana; Castelo-Branco, Miguel; Voon, Valerie

    2015-03-13

    The compulsive behaviour underlying obsessive-compulsive disorder (OCD) may be related to abnormalities in decision-making. The inability to commit to ultimate decisions, for example, patients unable to decide whether their hands are sufficiently clean, may reflect failures in accumulating sufficient evidence before a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination, hypothesizing enhanced evidence accumulation relative to healthy volunteers. Twenty-eight OCD patients and thirty-five controls were tested with a low-level visual perceptual task (random-dot-motion task, RDMT) and two response conflict control tasks. Regression analysis across different motion coherence levels and Hierarchical Drift Diffusion Modelling (HDDM) were used to characterize response strategies between groups in the RDMT. Patients required more evidence under high uncertainty perceptual contexts, as indexed by longer response time and higher decision boundaries. HDDM, which defines a decision when accumulated noisy evidence reaches a decision boundary, further showed slower drift rate towards the decision boundary reflecting poorer quality of evidence entering the decision process in patients under low uncertainty. With monetary incentives emphasizing speed and penalty for slower responses, patients decreased the decision thresholds relative to controls, accumulating less evidence in low uncertainty. These findings were unrelated to visual perceptual deficits and response conflict. This study provides evidence for impaired decision-formation processes in OCD, with a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). It further emphasizes that OCD patients are sensitive to monetary incentives heightening speed in the speed-accuracy tradeoff, improving evidence accumulation.

  18. Pros and cons of CLA consumption: an insight from clinical evidences.

    PubMed

    Benjamin, Sailas; Prakasan, Priji; Sreedharan, Sajith; Wright, Andre-Denis G; Spener, Friedrich

    2015-01-01

    This comprehensive review critically evaluates whether supposed health benefits propounded upon human consumption of conjugated linoleic acids (CLAs) are clinically proven or not. With a general introduction on the chemistry of CLA, major clinical evidences pertaining to intervention strategies, body composition, cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated. Supposed adverse effects such as oxidative stress, insulin resistance, irritation of intestinal tract and milk fat depression are also examined. It seems that no consistent result was observed even in similar studies conducted at different laboratories, this may be due to variations in age, gender, racial and geographical disparities, coupled with type and dose of CLA supplemented. Thus, supposed promising results reported in mechanistic and pre-clinical studies cannot be extrapolated with humans, mainly due to the lack of inconsistency in analyses, prolonged intervention studies, follow-up studies and international co-ordination of concerted studies. Briefly, clinical evidences accumulated thus far show that CLA is not eliciting significantly promising and consistent health effects so as to uphold it as neither a functional nor a medical food.

  19. An evidence accumulation model for conflict detection performance in a simulated air traffic control task.

    PubMed

    Neal, Andrew; Kwantes, Peter J

    2009-04-01

    The aim of this article is to develop a formal model of conflict detection performance. Our model assumes that participants iteratively sample evidence regarding the state of the world and accumulate it over time. A decision is made when the evidence reaches a threshold that changes over time in response to the increasing urgency of the task. Two experiments were conducted to examine the effects of conflict geometry and timing on response proportions and response time. The model is able to predict the observed pattern of response times, including a nonmonotonic relationship between distance at point of closest approach and response time, as well as effects of angle of approach and relative velocity. The results demonstrate that evidence accumulation models provide a good account of performance on a conflict detection task. Evidence accumulation models are a form of dynamic signal detection theory, allowing for the analysis of response times as well as response proportions, and can be used for simulating human performance on dynamic decision tasks.

  20. What is value—accumulated reward or evidence?

    PubMed Central

    Friston, Karl; Adams, Rick; Montague, Read

    2012-01-01

    Why are you reading this abstract? In some sense, your answer will cast the exercise as valuable—but what is value? In what follows, we suggest that value is evidence or, more exactly, log Bayesian evidence. This implies that a sufficient explanation for valuable behavior is the accumulation of evidence for internal models of our world. This contrasts with normative models of optimal control and reinforcement learning, which assume the existence of a value function that explains behavior, where (somewhat tautologically) behavior maximizes value. In this paper, we consider an alternative formulation—active inference—that replaces policies in normative models with prior beliefs about the (future) states agents should occupy. This enables optimal behavior to be cast purely in terms of inference: where agents sample their sensorium to maximize the evidence for their generative model of hidden states in the world, and minimize their uncertainty about those states. Crucially, this formulation resolves the tautology inherent in normative models and allows one to consider how prior beliefs are themselves optimized in a hierarchical setting. We illustrate these points by showing that any optimal policy can be specified with prior beliefs in the context of Bayesian inference. We then show how these prior beliefs are themselves prescribed by an imperative to minimize uncertainty. This formulation explains the saccadic eye movements required to read this text and defines the value of the visual sensations you are soliciting. PMID:23133414

  1. An Accumulation-of-Evidence Task Using Visual Pulses for Mice Navigating in Virtual Reality

    PubMed Central

    Pinto, Lucas; Koay, Sue A.; Engelhard, Ben; Yoon, Alice M.; Deverett, Ben; Thiberge, Stephan Y.; Witten, Ilana B.; Tank, David W.; Brody, Carlos D.

    2018-01-01

    The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts. PMID:29559900

  2. Dopamine Modulates the Efficiency of Sensory Evidence Accumulation During Perceptual Decision Making.

    PubMed

    Beste, Christian; Adelhöfer, Nico; Gohil, Krutika; Passow, Susanne; Roessner, Veit; Li, Shu-Chen

    2018-04-02

    Perceptual decision making is the process through which available sensory information is gathered and processed to guide our choices. However, the neuropsychopharmacological basis of this important cognitive function is largely elusive. Yet, theoretical considerations suggest that the dopaminergic system may play an important role. In a double-blind, randomized, placebo-controlled study design, we examined the effect of methylphenidate in 2 dosages (0.25 mg/kg and 0.5 mg/kg body weight) in separate groups of healthy young adults. We used a moving dots task in which the coherency of the direction of moving dots stimuli was manipulated in 3 levels (5%, 15%, and 35%). Drift diffusion modelling was applied to behavioral data to capture subprocesses of perceptual decision making. The findings show that only the drift rate (v), reflecting the efficiency of sensory evidence accumulation, but not the decision criterion threshold (a) or the duration of nondecisional processes (Ter), is affected by methylphenidate vs placebo administration. Compared with placebo, administering 0.25 mg/kg methylphenidate increased v, but only in the 35% coherence condition. Administering 0.5 mg/kg methylphenidate did not induce modulations. The data suggest that dopamine selectively modulates the efficacy of evidence accumulation during perceptual decision making. This modulation depends on 2 factors: (1) the degree to which the dopaminergic system is modulated using methylphenidate (i.e., methylphenidate dosage) and (2) the signal-to-noise ratio of the visual information. Dopamine affects sensory evidence accumulation only when dopamine concentration is not shifted beyond an optimal level and the incoming information is less noisy.

  3. The key-features approach to assess clinical decisions: validity evidence to date.

    PubMed

    Bordage, G; Page, G

    2018-05-17

    The key-features (KFs) approach to assessment was initially proposed during the First Cambridge Conference on Medical Education in 1984 as a more efficient and effective means of assessing clinical decision-making skills. Over three decades later, we conducted a comprehensive, systematic review of the validity evidence gathered since then. The evidence was compiled according to the Standards for Educational and Psychological Testing's five sources of validity evidence, namely, Content, Response process, Internal structure, Relations to other variables, and Consequences, to which we added two other types related to Cost-feasibility and Acceptability. Of the 457 publications that referred to the KFs approach between 1984 and October 2017, 164 are cited here; the remaining 293 were either redundant or the authors simply mentioned the KFs concept in relation to their work. While one set of articles reported meeting the validity standards, another set examined KFs test development choices and score interpretation. The accumulated validity evidence for the KFs approach since its inception supports the decision-making construct measured and its use to assess clinical decision-making skills at all levels of training and practice and with various types of exam formats. Recognizing that gathering validity evidence is an ongoing process, areas with limited evidence, such as item factor analyses or consequences of testing, are identified as well as new topics needing further clarification, such as the use of the KFs approach for formative assessment and its place within a program of assessment.

  4. Accumulating Evidence and Research Organization (AERO) model: a new tool for representing, analyzing, and planning a translational research program.

    PubMed

    Hey, Spencer Phillips; Heilig, Charles M; Weijer, Charles

    2013-05-30

    Maximizing efficiency in drug development is important for drug developers, policymakers, and human subjects. Limited funds and the ethical imperative of risk minimization demand that researchers maximize the knowledge gained per patient-subject enrolled. Yet, despite a common perception that the current system of drug development is beset by inefficiencies, there remain few approaches for systematically representing, analyzing, and communicating the efficiency and coordination of the research enterprise. In this paper, we present the first steps toward developing such an approach: a graph-theoretic tool for representing the Accumulating Evidence and Research Organization (AERO) across a translational trajectory. This initial version of the AERO model focuses on elucidating two dimensions of robustness: (1) the consistency of results among studies with an identical or similar outcome metric; and (2) the concordance of results among studies with qualitatively different outcome metrics. The visual structure of the model is a directed acyclic graph, designed to capture these two dimensions of robustness and their relationship to three basic questions that underlie the planning of a translational research program: What is the accumulating state of total evidence? What has been the translational trajectory? What studies should be done next? We demonstrate the utility of the AERO model with an application to a case study involving the antibacterial agent, moxifloxacin, for the treatment of drug-susceptible tuberculosis. We then consider some possible elaborations for the AERO model and propose a number of ways in which the tool could be used to enhance the planning, reporting, and analysis of clinical trials. The AERO model provides an immediate visual representation of the number of studies done at any stage of research, depicting both the robustness of evidence and the relationship of each study to the larger translational trajectory. In so doing, it makes some of the

  5. The nitrogen legacy: emerging evidence of nitrogen accumulation in anthropogenic landscapes

    NASA Astrophysics Data System (ADS)

    Van Meter, K. J.; Basu, N. B.; Veenstra, J. J.; Burras, C. L.

    2016-03-01

    Watershed and global-scale nitrogen (N) budgets indicate that the majority of the N surplus in anthropogenic landscapes does not reach the coastal oceans. While there is general consensus that this ‘missing’ N either exits the landscape via denitrification or is retained within watersheds as nitrate or organic N, the relative magnitudes of these pools and fluxes are subject to considerable uncertainty. Our study, for the first time, provides direct, large-scale evidence of N accumulation in the root zones of agricultural soils that may account for much of the ‘missing N’ identified in mass balance studies. We analyzed long-term soil data (1957-2010) from 2069 sites throughout the Mississippi River Basin (MRB) to reveal N accumulation in cropland of 25-70 kg ha-1 yr-1, a total of 3.8 ± 1.8 Mt yr-1 at the watershed scale. We then developed a simple modeling framework to capture N depletion and accumulation dynamics under intensive agriculture. Using the model, we show that the observed accumulation of soil organic N (SON) in the MRB over a 30 year period (142 Tg N) would lead to a biogeochemical lag time of 35 years for 99% of legacy SON, even with complete cessation of fertilizer application. By demonstrating that agricultural soils can act as a net N sink, the present work makes a critical contribution towards the closing of watershed N budgets.

  6. Finding and applying evidence during clinical rounds: the "evidence cart".

    PubMed

    Sackett, D L; Straus, S E

    1998-10-21

    Physicians need easy access to evidence for clinical decisions while they care for patients but, to our knowledge, no investigators have assessed use of evidence during rounds with house staff. To determine if it was feasible to find and apply evidence during clinical rounds, using an "evidence cart" that contains multiple sources of evidence and the means for projecting and printing them. Descriptive feasibility study of use of evidence during 1 month (April 1997) and anonymous questionnaire (May 1997). General medicine inpatient service. Medical students, house staff, fellows, and attending consultant. Evidence cart that included 2 secondary sources developed by the department (critically appraised topics [CATs] and Redbook), Best Evidence, JAMA Rational Clinical Examination series, the Cochrane Library, MEDLINE, a physical examination textbook, a radiology anatomy textbook, and a Simulscope, which allows several people to listen simultaneously to the same signs on physical examination. Number of times sources were used, type of sources searched and success of searches, time needed to search, and whether the search affected patient care. The evidence cart was used 98 times, but could not be taken on bedside rounds because of its bulk; hard copies of several sources were taken instead. When the evidence cart was used during team rounds and student rounds, some sources could be accessed quickly enough (10.2-25.4 seconds) to be practical on our service. Of 98 searches, 79 (81%) sought evidence that could affect diagnostic and/or treatment decisions. Seventy-one (90%) of 79 searches regarding patient management were successful, and when assessed from the perspective of the most junior team members responsible for each patient's evaluation and management, 37 (52%) of the 71 successful searches confirmed their current or tentative diagnostic or treatment plans, 18 (25%) led to a new diagnostic skill, an additional test, or a new management decision, and 16 (23

  7. Challenges in acute heart failure clinical management: optimizing care despite incomplete evidence and imperfect drugs.

    PubMed

    Teichman, Sam L; Maisel, Alan S; Storrow, Alan B

    2015-03-01

    Acute heart failure is a common condition associated with considerable morbidity, mortality, and cost. However, evidence-based data on treating heart failure in the acute setting are limited, and current individual treatment options have variable efficacy. The healthcare team must often individualize patient care in ways that may extend beyond available clinical guidelines. In this review, we address the question, "How do you do the best you can clinically with incomplete evidence and imperfect drugs?" Expert opinion is provided to supplement guideline-based recommendations and help address the typical challenges that are involved in the management of patients with acute heart failure. Specifically, we discuss 4 key areas that are important in the continuum of patient care: differential diagnosis and risk stratification; choice and implementation of initial therapy; assessment of the adequacy of therapy during hospitalization or observation; and considerations for discharge/transition of care. A case study is presented to highlight the decision-making process throughout each of these areas. Evidence is accumulating that should help guide patients and healthcare providers on a path to better quality of care.

  8. Clinical librarians as facilitators of nurses' evidence-based practice.

    PubMed

    Määttä, Sylvia; Wallmyr, Gudrun

    2010-12-01

    The aim of this study was to explore nurses' and ward-based clinical librarians' reflections on ward-based clinical librarians as facilitators for nurses' use of evidences-based practice. Nurses' use of evidence-based practice is reported to be weak. Studies have suggested that clinical librarians may promote evidence-based practice. To date, little is known about clinical librarians participating nurses in the wards. A descriptive, qualitative design was adopted for the study. In 2007, 16 nurses who had been attended by a clinical librarian in the wards were interviewed in focus groups. Two clinical librarians were interviewed by individual interviews. In the analysis, a content analysis was used. Three themes were generated from the interviews with nurses: 'The grip of everyday work', 'To articulate clinical nursing issues' and 'The clinical librarians at a catalyst'. The nurses experienced the grip of everyday work as a hindrance and had difficulties to articulate and formulate relevant nursing issues. In such a state, the nurses found the clinical librarian presence in the ward as enhancing the awareness of and the use of evidence-based practice. Three themes emerged from the analysis with the librarians. They felt as outsiders, had new knowledge and acquired a new role as ward-based clinical librarians. Facilitation is needed if nurses' evidence-based practice is going to increase. The combined use of nurses and clinical librarians' knowledge and skills can be optimised. To achieve this, nurses' skills in consuming and implementing evidence ought to be strengthened. The fusion of the information and knowledge management skill of the ward-based clinical librarian and the clinical expertise of the nurses can be of value. With such a collaborative model, nurse and ward-based clinical librarian might join forces to increase the use of evidence-based practice. © 2010 Blackwell Publishing Ltd.

  9. Evidence for gas accumulation associated with diapirism and gas hydrates at the head of the Cape Fear Slide

    USGS Publications Warehouse

    Schmuck, E.A.; Paull, C.K.

    1993-01-01

    Single-channel seismic reflection profiles show evidence for areas of significant gas accumulation at the head of the Cape Fear Slide on the continental rise oft North Carolina. Gas accumulation appears to occur beneath a gas hydrate seal in landward-dipping strata and in domed strata associated with diapirism. In addition, gas venting may have occurred near diapirs located at the head of the slide.

  10. Clinical Evidence: a useful tool for promoting evidence-based practice?

    PubMed

    Formoso, Giulio; Moja, Lorenzo; Nonino, Francesco; Dri, Pietro; Addis, Antonio; Martini, Nello; Liberati, Alessandro

    2003-12-23

    Research has shown that many healthcare professionals have problems with guidelines as they would prefer to be given all relevant information relevant to decision-making rather than being told what they should do. This study assesses doctors' judgement of the validity, relevance, clarity and usability of the Italian translation of Clinical Evidence (CE) after its free distribution launched by the Italian Ministry of Health. Opinions elicited using a standardised questionnaire delivered either by mail or during educational or professional meetings. Twenty percent (n = 1350) doctors participated the study. Most of them found CE's content valid, useful and relevant for their clinical practice, and said CE can foster communications among clinicians, particularly among GPs and specialists. Hospital doctors (63%) more often than GPs (48%) read the detailed presentation of individual chapters. Twenty-nine percent said CE brought changes in their clinical practice. Doctors appreciated CE's nature of an evidence-based information compendium and would have not preferred a collection of practice guidelines. Overall, the pilot initiative launched by the Italian Ministry of Health seems to have been well received and to support the subsequent decision to make the Italian edition of Clinical Evidence concise available to all doctors practising in the country. Local implementation initiatives should be warranted to favour doctor's use of CE.

  11. Evidence for gas accumulation associated with diapirism and gas hydrates at the head of the Cape Fear Slide

    USGS Publications Warehouse

    Schmuck, E.A.; Paull, C.K.

    1993-01-01

    Single-channel seismic reflection profiles show evidence for areas of significant gas accumulation at the head of the Cape Fear Slide on the continental rise off North Carolina. Gas accumulation appears to occur beneath a gas hydrate seal in landward-dipping strata and in domed strata associated with diapirism. In addition, gas venting may have occurred near diapirs located at the head of the slide. ?? 1993 Springer-Verlag.

  12. How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

    PubMed

    Naci, Huseyin; Ioannidis, John P A

    2015-01-01

    Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

  13. Rapid temporal accumulation in spider fear: Evidence from hierarchical drift diffusion modelling.

    PubMed

    Tipples, Jason

    2015-12-01

    Fear can distort sense of time--making time seem slow or even stand still. Here, I used hierarchical drift diffusion modeling (HDDM; Vandekerckhove, Tuerlinckx, & Lee, 2008, 2011; Wiecki, Sofer, & Frank, 2013) to test the idea that temporal accumulation speeds up during fear. Eighteen high fearful and 23 low fearful participants judged the duration of both feared stimuli (spiders) and nonfeared stimuli (birds) in a temporal bisection task. The drift diffusion modeling results support the main hypothesis. In high but not low fearful individuals, evidence accumulated more rapidly toward a long duration decision-drift rates were higher-for spiders compared with birds. This result and further insights into how fear affects time perception would not have been possible on the basis of analyses of choice proportion data alone. Further results were interpreted in the context of a recent 2-stage model of time perception (Balcı & Simen, 2014). The results highlight the usefulness of diffusion modeling to test process-based explanations of disordered cognition in emotional disorders. (c) 2015 APA, all rights reserved).

  14. Evidence Accumulation and Change Rate Inference in Dynamic Environments.

    PubMed

    Radillo, Adrian E; Veliz-Cuba, Alan; Josić, Krešimir; Kilpatrick, Zachary P

    2017-06-01

    In a constantly changing world, animals must account for environmental volatility when making decisions. To appropriately discount older, irrelevant information, they need to learn the rate at which the environment changes. We develop an ideal observer model capable of inferring the present state of the environment along with its rate of change. Key to this computation is an update of the posterior probability of all possible change point counts. This computation can be challenging, as the number of possibilities grows rapidly with time. However, we show how the computations can be simplified in the continuum limit by a moment closure approximation. The resulting low-dimensional system can be used to infer the environmental state and change rate with accuracy comparable to the ideal observer. The approximate computations can be performed by a neural network model via a rate-correlation-based plasticity rule. We thus show how optimal observers accumulate evidence in changing environments and map this computation to reduced models that perform inference using plausible neural mechanisms.

  15. Creatinine concentrations of accumulated intrauterine fluid to confirm the clinical diagnosis of urometra in mares.

    PubMed

    Schnobrich, M R; Gordon, D L; Scoggin, C F; Bradecamp, E A; Canisso, I F

    2017-03-25

    Urine pooling, as a persistent condition, is a cause of infertility in mares due to endometrial inflammation and sperm toxicity. Identification of urometra can be challenging in mares presenting with the condition intermittently, or when urine flows into the uterus but is undetectable in the vagina. Currently, there are no reported objective methods to confirm the clinical diagnosis of urine contamination in intrauterine-fluid accumulations. Since creatinine is present in high concentrations in urine and does not diffuse across cell membranes, creatinine concentration should be increased in mares with urometra, but negligible in normal and mares with intrauterine fluid accumulation (non-urometra cases). To test this hypothesis, creatinine concentrations of intrauterine fluid were measured in mares with a clinical diagnosis of urine accumulation (n=9) or intrauterine fluid containing no urine (n=10). Results showed that creatinine concentrations (mg/dl) were significantly higher in mares that had a clinical diagnosis of urometra (42.8±12.6, range 4.1-109.2) compared with those that did not (0.38±0.1, range 0-0.9). Also, two mares after urethral extension surgery demonstrated a remarkable reduction in creatinine concentrations. This study highlights an undocumented approach to confirm a clinical diagnosis of urometra in mares; the authors anticipate that testing for creatinine in the uterine fluid of mares may become a standard tool for identifying urometra in mares and confirming the success of urogenital surgeries. British Veterinary Association.

  16. Evidence-based clinical practice, [corrected] evidence-based medicine and the Cochrane collaboration.

    PubMed

    Gambrill, E

    1999-03-01

    Encouraging professionals in training and later to consider practice-related research findings when making important clinical decisions is an on-going concern. Evidenced-Based Medicine (EBM) and the Cochrane Collaboration (CC) provide a source of tools and ideas for doing so, as well as a roster of colleagues who share this interest. Evidenced-based medicine involves integrating clinical expertise with the best available external evidence from systematic research as well as considering the values and expectations of patients/clients. Advantage can be taken of educational formats developed in EBM, such as problem-based learning and critical-appraisal workshops in which participants learn how to ask key answerable questions related to important clinical practice questions (e.g., regarding effectiveness, accuracy of assessment measures, prediction, prevention, and quality of clinical practice guidelines) and to access and critically appraise related research. The Cochrane Collaboration is a world-wide network of centers that prepare, maintain, and disseminate high-quality systematic reviews on the efficacy of healthcare. These databases allow access to evidence related to clinical practice decisions. Forging reciprocal working relationships with those involved in EBM reciprocal and the CC should contribute to the pursuit of shared goals such as basing clinical decisions on the best-available evidence and involving clients as informed consumers.

  17. Extending the Reach of Evidence-Based Medicine: A Proposed Categorization of Lower-Level Evidence.

    PubMed

    Detterbeck, Frank C; Gould, Michael K; Lewis, Sandra Zelman; Patel, Sheena

    2018-02-01

    Clinical practice involves making many treatment decisions for which only limited formal evidence exists. While the methodology of evidence-based medicine (EBM) has evolved tremendously, there is a need to better characterize lower-level evidence. This should enhance the ability to appropriately weigh the evidence against other considerations, and counter the temptation to think it is more robust than it actually is. A framework to categorize lower-level evidence is proposed, consisting of nonrandomized comparisons, extrapolation using indirect evidence, rationale, and clinical experience (ie, an accumulated general impression). Subtypes are recognized within these categories, based on the degree of confounding in nonrandomized comparisons, the uncertainty involved in extrapolation from indirect evidence, and the plausibility of a rationale. Categorizing the available evidence in this way can promote a better understanding of the strengths and limitations of using such evidence as the basis for treatment decisions in clinically relevant areas that are devoid of higher-level evidence. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. RELATING ACCUMULATOR MODEL PARAMETERS AND NEURAL DYNAMICS

    PubMed Central

    Purcell, Braden A.; Palmeri, Thomas J.

    2016-01-01

    Accumulator models explain decision-making as an accumulation of evidence to a response threshold. Specific model parameters are associated with specific model mechanisms, such as the time when accumulation begins, the average rate of evidence accumulation, and the threshold. These mechanisms determine both the within-trial dynamics of evidence accumulation and the predicted behavior. Cognitive modelers usually infer what mechanisms vary during decision-making by seeing what parameters vary when a model is fitted to observed behavior. The recent identification of neural activity with evidence accumulation suggests that it may be possible to directly infer what mechanisms vary from an analysis of how neural dynamics vary. However, evidence accumulation is often noisy, and noise complicates the relationship between accumulator dynamics and the underlying mechanisms leading to those dynamics. To understand what kinds of inferences can be made about decision-making mechanisms based on measures of neural dynamics, we measured simulated accumulator model dynamics while systematically varying model parameters. In some cases, decision- making mechanisms can be directly inferred from dynamics, allowing us to distinguish between models that make identical behavioral predictions. In other cases, however, different parameterized mechanisms produce surprisingly similar dynamics, limiting the inferences that can be made based on measuring dynamics alone. Analyzing neural dynamics can provide a powerful tool to resolve model mimicry at the behavioral level, but we caution against drawing inferences based solely on neural analyses. Instead, simultaneous modeling of behavior and neural dynamics provides the most powerful approach to understand decision-making and likely other aspects of cognition and perception. PMID:28392584

  19. Visuospatial Asymmetries Arise from Differences in the Onset Time of Perceptual Evidence Accumulation.

    PubMed

    Newman, Daniel P; Loughnane, Gerard M; Kelly, Simon P; O'Connell, Redmond G; Bellgrove, Mark A

    2017-03-22

    Healthy subjects tend to exhibit a bias of visual attention whereby left hemifield stimuli are processed more quickly and accurately than stimuli appearing in the right hemifield. It has long been held that this phenomenon arises from the dominant role of the right cerebral hemisphere in regulating attention. However, methods that would enable more precise understanding of the mechanisms underpinning visuospatial bias have remained elusive. We sought to finely trace the temporal evolution of spatial biases by leveraging a novel bilateral dot motion detection paradigm. In combination with electroencephalography, this paradigm enables researchers to isolate discrete neural signals reflecting the key neural processes needed for making these detection decisions. These include signals for spatial attention, early target selection, evidence accumulation, and motor preparation. Using this method, we established that three key neural markers accounted for unique between-subject variation in visuospatial bias: hemispheric asymmetry in posterior α power measured before target onset, which is related to the distribution of preparatory attention across the visual field; asymmetry in the peak latency of the early N2c target-selection signal; and, finally, asymmetry in the onset time of the subsequent neural evidence-accumulation process with earlier onsets for left hemifield targets. Our development of a single paradigm to dissociate distinct processing components that track the temporal evolution of spatial biases not only advances our understanding of the neural mechanisms underpinning normal visuospatial attention bias, but may also in the future aid differential diagnoses in disorders of spatial attention. SIGNIFICANCE STATEMENT The significance of this research is twofold. First, it shows that individual differences in how humans direct their attention between left and right space reflects physiological differences in how early the brain starts to accumulate evidence for

  20. Evidence based practice in clinical physiotherapy education: a qualitative interpretive description.

    PubMed

    Olsen, Nina R; Bradley, Peter; Lomborg, Kirsten; Nortvedt, Monica W

    2013-04-11

    Health care undergraduate students are expected to practice evidence-based after they graduate. Previous research indicates that students face several problems with transferring evidence-based practice to real patient situations. Few studies have explored reasons for this. The aim of this study was to explore beliefs, experiences and attitudes related to third year students' use of evidence-based practice in clinical physiotherapy education among students, clinical instructors and visiting teachers. In total, six focus group interviews were conducted: three with 16 students, two with nine clinical instructors and one with four visiting teachers. In addition, one individual interview and one interview in a pair were conducted with clinical instructors. Interviewing three different participant-categories ensured comparative analysis and enabled us to exploit differences in perspectives and interactions. Interpretive description guided this process. Four integrative themes emerged from the analysis: "attempt to apply evidence-based practice", "novices in clinical practice", "prioritize practice experience over evidence-based practice" and "lack role models in evidence-based practice". Students tried to search for research evidence and to apply this knowledge during clinical placements; a behaviour that indicated a positive attitude towards evidence-based practice. At the same time, students were novices and required basic background information more than research information. As novices they tended to lean on their clinical instructors, and were more eager to gain practical experience than practicing evidence-based; a behaviour that clinical instructors and visiting teachers often supported. Students noticed a lack of an EBP culture. Both students and clinical instructors perceived a need for role models in evidence-based practice. Clinical instructors are in a position to influence students during clinical education, and thus, important potential role models in

  1. Evidence based practice in clinical physiotherapy education: a qualitative interpretive description

    PubMed Central

    2013-01-01

    Background Health care undergraduate students are expected to practice evidence-based after they graduate. Previous research indicates that students face several problems with transferring evidence-based practice to real patient situations. Few studies have explored reasons for this. The aim of this study was to explore beliefs, experiences and attitudes related to third year students’ use of evidence-based practice in clinical physiotherapy education among students, clinical instructors and visiting teachers. Methods In total, six focus group interviews were conducted: three with 16 students, two with nine clinical instructors and one with four visiting teachers. In addition, one individual interview and one interview in a pair were conducted with clinical instructors. Interviewing three different participant-categories ensured comparative analysis and enabled us to exploit differences in perspectives and interactions. Interpretive description guided this process. Results Four integrative themes emerged from the analysis: “attempt to apply evidence-based practice”, “novices in clinical practice”, “prioritize practice experience over evidence-based practice” and “lack role models in evidence-based practice”. Students tried to search for research evidence and to apply this knowledge during clinical placements; a behaviour that indicated a positive attitude towards evidence-based practice. At the same time, students were novices and required basic background information more than research information. As novices they tended to lean on their clinical instructors, and were more eager to gain practical experience than practicing evidence-based; a behaviour that clinical instructors and visiting teachers often supported. Students noticed a lack of an EBP culture. Both students and clinical instructors perceived a need for role models in evidence-based practice. Conclusions Clinical instructors are in a position to influence students during clinical

  2. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  3. Evidence-based health care: its place within clinical governance.

    PubMed

    McSherry, R; Haddock, J

    This article explores the principles of evidence-based practice and its role in achieving quality improvements within the clinical governance framework advocated by the recent White Papers 'The New NHS: Modern, Dependable' (Department of Health (DoH), 1997) and 'A First Class Service: Quality in the New NHS' (DoH, 1998a). Within these White Papers there is an emphasis on improving quality of care, treatment and services through employing the principles of clinical governance. A major feature of clinical governance is guaranteeing quality to the public and the NHS, and ensuring that clinical, managerial and educational practice is based on scientific evidence. This article also examines what evidence-based practice is and what processes are required to promote effective healthcare interventions. The authors also look at how clinical governance relates to other methods/systems involved in clinical effectiveness. Finally, the importance for nurses and other healthcare professionals of familiarizing themselves with the development of critical appraisal skills, and their implications for developing evidence-based practice, is emphasized.

  4. A practical approach to evidence-based dentistry: How to search for evidence to inform clinical decisions.

    PubMed

    Brignardello-Petersen, Romina; Carrasco-Labra, Alonso; Booth, H Austin; Glick, Michael; Guyatt, Gordon H; Azarpazhooh, Amir; Agoritsas, Thomas

    2014-12-01

    Knowing how to search for evidence that can inform clinical decisions is a fundamental skill for the practice of evidence-based dentistry. There are many available types of evidence-based resources, characterized by their degrees of coverage of preappraised or summarized evidence at varying levels of processing, from primary studies to systematic reviews and clinical guidelines. The practice of evidence-based dentistry requires familiarity with these resources. In this article, the authors describe the process of searching for evidence: defining the question, identifying the question's nature and main components, and selecting the study design that best addresses the question.

  5. Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice.

    PubMed

    Hajjaj, F M; Salek, M S; Basra, M K A; Finlay, A Y

    2010-05-01

    This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine.

  6. [Evidence-based aspects of clinical mastitis treatment].

    PubMed

    Mansion-de Vries, E M; Hoedemaker, M; Krömker, V

    2015-01-01

    Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence-based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i.   e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents.

  7. An innovative clinical practicum to teach evidence-based practice.

    PubMed

    Brancato, Vera C

    2006-01-01

    A clinical practicum was successfully implemented for RN to BSN students to apply evidence-based practice to actual clinical problems affecting nursing practice. The author describes how this practicum was implemented and the requisite resources and support systems. This senior-level capstone course enabled students to understand and value a lifelong learning approach to evidence-based practice.

  8. Pulmonary accumulation of polymorphonuclear leukocytes in the adult respiratory distress syndrome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Powe, J.E.; Short, A.; Sibbald, W.J.

    1982-11-01

    The polymorphonuclear leukocyte (PMN) plays an integral role in the development of permeability pulmonary edema associated with the adult respiratory distress syndrome (ARDS). This report describes 3 patients with ARDS secondary to systemic sepsis who demonstrated an abnormal diffuse accumulation of Indium (/sup 111/In)-labeled PMNs in their lungs, without concomitant clinical or laboratory evidence of a primary chest infection. In one patient, the accumulation of the pulmonary activity during an initial pass suggested that this observation was related to diffuse leukoaggregation within the pulmonary microvasculature. A 4th patient with ARDS was on high-dose corticosteroids at the time of a similarmore » study, and showed no pulmonary accumulation of PMNs, suggesting a possible reason for the reported beneficial effect of corticosteroids in human ARDS.« less

  9. An evidence-based guide to clinical instruction in audiology.

    PubMed

    Mormer, Elaine; Palmer, Catherine; Messick, Cheryl; Jorgensen, Lindsey

    2013-05-01

    A significant portion of the AuD curriculum occurs in clinical settings outside the classroom. Expert clinicians, employed within and outside of the university, are called upon to provide this clinical education. Most have had little or no formal training in clinical teaching yet face pedagogical and logistical challenges when simultaneously providing clinical service and teaching. Training to provide optimal methods and approaches to clinical instruction should be based on research evidence; however, there is a paucity of research in this area within the audiology discipline. This article provides a review of literature supplying evidence for important concepts, elements, and approaches to the clinical instruction process. Additionally, we provide readers with some practical tools with which to facilitate application of optimal clinical teaching principles. We conducted a systematic review of literature on clinical education in audiology and across a wide array of health professions. Through the use of content analysis we identified four elements of the clinical teaching process most critical in examining optimal practices. The elements identified as critical to positive clinical learning outcomes include the establishment of mutual expectations and goals; structured content and delivery of feedback; establishment of a positive instructor/student relationship; and questioning strategies that lead to the development of critical thinking skills. Many disciplines outside of audiology demonstrate robust research activity related to understanding and optimizing the clinical education process. The application of a number of evidence-based clinical teaching principles should allow us to improve student outcomes in audiology. Researchers in our field might consider if and how we should develop our own research literature in clinical education. American Academy of Audiology.

  10. Exploring the contribution of the Clinical Librarian to facilitating evidence-based nursing.

    PubMed

    Tod, Angela M; Bond, Beverly; Leonard, Niamh; Gilsenan, Irene J; Palfreyman, Simon

    2007-04-01

    To examine the potential role of the Clinical Librarian in facilitating evidence-based practice of nurses in acute hospital settings and develop a model for the role. There is a growing policy and professional expectation that nurses will seek out and apply evidence in their clinical practice. Studies have demonstrated that nurses experience barriers in working with an evidence-based approach. The role of Clinical Librarian has been used in other countries and within medicine to overcome some of the barriers to evidence-based practice. There are limitations in the previous work in terms of rigour of evaluation, scope of the Clinical Librarian role and application to nursing in a UK setting. A qualitative consultation of 72 nurses in acute care settings. Six consultation group interviews of between 4-19 participants. Written records were recorded by the scribe. Content analysis was undertaken to identify the range and frequency of comments. Clinical questions currently go unanswered because of barriers of time, skills deficits and access to resources. Literature searching, skills training and evidence dissemination were the main areas of work the staff requested that a Clinical Librarian should undertake. It was anticipated that the Clinical Librarian could interact and work productively with nursing staff with a limited but regular presence on the ward. Interim communication could be via e-mail, phone and written suggestions and requests for work. It was seen to be vital that the Clinical Librarian worked in partnership with staff to build evidence-based practice capacity and ensure clinical relevance of the work. This study has generated the first model for the Clinical Librarian role with an emphasis on nursing. It is derived from the views of clinical nurses. Recommendations are made for the implementation and evaluation of such a role. The Clinical Librarian could be an invaluable support to promoting evidence-based nursing.

  11. Evidence-Based Clinical Voice Assessment: A Systematic Review

    ERIC Educational Resources Information Center

    Roy, Nelson; Barkmeier-Kraemer, Julie; Eadie, Tanya; Sivasankar, M. Preeti; Mehta, Daryush; Paul, Diane; Hillman, Robert

    2013-01-01

    Purpose: To determine what research evidence exists to support the use of voice measures in the clinical assessment of patients with voice disorders. Method: The American Speech-Language-Hearing Association (ASHA) National Center for Evidence-Based Practice in Communication Disorders staff searched 29 databases for peer-reviewed English-language…

  12. Robotic surgery: current perceptions and the clinical evidence.

    PubMed

    Ahmad, Arif; Ahmad, Zoha F; Carleton, Jared D; Agarwala, Ashish

    2017-01-01

    It appears that a discrepancy exists between the perception of robotic-assisted surgery (RAS) and the current clinical evidence regarding robotic-assisted surgery among patients, healthcare providers, and hospital administrators. The purpose of this study was to assess whether or not such a discrepancy exists. We administered survey questionnaires via face-to-face interviews with surgical patients (n = 101), healthcare providers (n = 58), and senior members of hospital administration (n = 6) at a community hospital that performs robotic surgery. The respondents were asked about their perception regarding the infection rate, operative time, operative blood loss, incision size, cost, length of hospital stay (LOS), risk of complications, precision and accuracy, tactile sensation, and technique of robotic-assisted surgery as compared with conventional laparoscopic surgery. We then performed a comprehensive literature review to assess whether or not these perceptions could be corroborated with clinical evidence. The majority of survey respondents perceived RAS as modality to decrease infection rate, increase operative time, decrease operative blood loss, smaller incision size, a shorter LOS, and a lower risk of complications, while increasing the cost. Respondents also believed that robotic surgery provides greater precision, accuracy, and tactile sensation, while improving intra-operative access to organs. A comprehensive literature review found little-to-no clinical evidence that supported the respondent's favorable perceptions of robotic surgery except for the increased costs, and precision and accuracy of the robotic-assisted technique. There is a discrepancy between the perceptions of robotic surgery and the clinical evidence among patients, healthcare providers, and hospital administrators surveyed.

  13. [The historical background and present development of evidence-based healthcare and clinical nursing].

    PubMed

    Tsai, Jung-Mei

    2014-12-01

    Evidence-based healthcare (EBHC) emphasizes the integration of the best research evidence with patient values, specialist suggestions, and clinical circumstances during the process of clinical decision-making. EBHC is a recognized core competency in modern healthcare. Nursing is a professional discipline of empirical science that thrives in an environment marked by advances in knowledge and technology in medicine as well as in nursing. Clinical nurses must elevate their skills and professional qualifications, provide efficient and quality health services, and promote their proficiency in EBHC. The Institute of Medicine in the United States indicates that evidence-based research results often fail to disseminate efficiently to clinical decision makers. This problem highlights the importance of better promoting the evidence-based healthcare fundamentals and competencies to frontline clinical nurses. This article describes the historical background and present development of evidence-based healthcare from the perspective of modern clinical nursing in light of the importance of evidence-based healthcare in clinical nursing; describes the factors associated with evidence-based healthcare promotion; and suggests strategies and policies that may improve the promotion and application of EBHC in clinical settings. The authors hope that this paper provides a reference for efforts to improve clinical nursing in the realms of EBHC training, promotion, and application.

  14. Evidence-based dentistry: a model for clinical practice.

    PubMed

    Faggion, Clóvis M; Tu, Yu-Kang

    2007-06-01

    Making decisions in dentistry should be based on the best evidence available. The objective of this study was to demonstrate a practical procedure and model that clinicians can use to apply the results of well-conducted studies to patient care by critically appraising the evidence with checklists and letter grade scales. To demonstrate application of this model for critically appraising the quality of research evidence, a hypothetical case involving an adult male with chronic periodontitis is used as an example. To determine the best clinical approach for this patient, a four-step, evidence-based model is demonstrated, consisting of the following: definition of a research question using the PICO format, search and selection of relevant literature, critical appraisal of identified research reports using checklists, and the application of evidence. In this model, the quality of research evidence was assessed quantitatively based on different levels of quality that are assigned letter grades of A, B, and C by evaluating the studies against the QUOROM (Quality of Reporting Meta-Analyses) and CONSORT (Consolidated Standards of Reporting Trials) checklists in a tabular format. For this hypothetical periodontics case, application of the model identified the best available evidence for clinical decision making, i.e., one randomized controlled trial and one systematic review of randomized controlled trials. Both studies showed similar answers for the research question. The use of a letter grade scale allowed an objective analysis of the quality of evidence. A checklist-driven model that assesses and applies evidence to dental practice may substantially improve dentists' decision making skill.

  15. Deterministic versus evidence-based attitude towards clinical diagnosis.

    PubMed

    Soltani, Akbar; Moayyeri, Alireza

    2007-08-01

    Generally, two basic classes have been proposed for scientific explanation of events. Deductive reasoning emphasizes on reaching conclusions about a hypothesis based on verification of universal laws pertinent to that hypothesis, while inductive or probabilistic reasoning explains an event by calculation of some probabilities for that event to be related to a given hypothesis. Although both types of reasoning are used in clinical practice, evidence-based medicine stresses on the advantages of the second approach for most instances in medical decision making. While 'probabilistic or evidence-based' reasoning seems to involve more mathematical formulas at the first look, this attitude is more dynamic and less imprisoned by the rigidity of mathematics comparing with 'deterministic or mathematical attitude'. In the field of medical diagnosis, appreciation of uncertainty in clinical encounters and utilization of likelihood ratio as measure of accuracy seem to be the most important characteristics of evidence-based doctors. Other characteristics include use of series of tests for refining probability, changing diagnostic thresholds considering external evidences and nature of the disease, and attention to confidence intervals to estimate uncertainty of research-derived parameters.

  16. Basic mechanisms of urgency: preclinical and clinical evidence.

    PubMed

    Michel, Martin C; Chapple, Christopher R

    2009-08-01

    Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

  17. Brokering the Evidence-Practice Gap: A Strategy for Moving Evidence Into Clinical Practice.

    PubMed

    Segre, Lisa S; Trusty, Stephanie; Gullickson, Renee; Chuffo Davila, Rebecca; O'Hara, Michael W

    2018-05-08

    Moving novel, evidence-based interventions into broad community use is challenging. This column describes how a midlevel public health administrator acted in the role of broker to link university-based researchers with maternal health clinical staff to successfully implement an innovative, evidence-based maternal depression treatment. Program evaluation assessed adoption, implementation, reach, and effectiveness. In reflecting on this partnership, the broker provided critical elements of access, credibility, and accountability. A partnership between service providers and research teams provides one strategy to disseminate evidence-based practices among those served by public-health programs.

  18. Evidence-based dentistry and clinical implementation by third-year dental students.

    PubMed

    Teich, Sorin T; Demko, Catherine A; Lang, Lisa A

    2013-10-01

    Over the last two decades, the concept of evidence-based medicine (EBM) has become the standard of medical care. Defined by Sackett et al. as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients," EBM recognizes that the practitioner should combine individual clinical expertise with the best available external evidence for optimal care. Consideration of the patient's needs and preferences is also an integral component of the clinical application. Dental educators have to account for the fact that not all dental treatment outcomes have been researched with randomized clinical trials. Dogmas in dentistry still exist regarding restorative treatments and methods taught to next generations of practitioners, while limited evidence is available. The purpose of this study was to determine how third-year dental students at one U.S. dental school select articles to provide supportive evidence related to treatment planning. The results show that knowledge provided in a three-week course in evidence-based dentistry (EBD) for first-year dental students was not efficiently applied when the students reached their third year. A significant percentage of the students perceived the use of literature as not beneficial for sustaining clinical aspects of a treatment plan, and they did not use appropriate tools to access best available resources. As a result of these findings, the article proposes incorporation of specific learning objectives related to EBD principles throughout the curriculum and a simplified method to search for best available evidence that has the advantage of not requiring knowledge and training in rigorous formulation of clinical questions.

  19. DynaMed Plus®: An Evidence-Based Clinical Reference Resource.

    PubMed

    Charbonneau, Deborah H; James, LaTeesa N

    2018-01-01

    DynaMed Plus ® from EBSCO Health is an evidence-based tool that health professionals can use to inform clinical care. DynaMed Plus content undergoes a review process, and the evidence is synthesized in detailed topic overviews. A unique three-level rating scale is used to assess the quality of available evidence. Topic overviews summarize current evidence and provide recommendations to support health providers at the point-of-care. Additionally, DynaMed Plus content can be accessed via a desktop computer or mobile platforms. Given this, DynaMed Plus can be a time-saving resource for health providers. Overall, DynaMed Plus provides evidence summaries using an easy-to-read bullet format, and the resource incorporates images, clinical calculators, patient handouts, and practice guidelines in one place.

  20. Everything should be as simple as possible, but no simpler: towards a protocol for accumulating evidence regarding the active content of health behaviour change interventions.

    PubMed

    Peters, Gjalt-Jorn Ygram; de Bruin, Marijn; Crutzen, Rik

    2015-01-01

    There is a need to consolidate the evidence base underlying our toolbox of methods of behaviour change. Recent efforts to this effect have conducted meta-regressions on evaluations of behaviour change interventions, deriving each method's effectiveness from its association to intervention effect size. However, there are a range of issues that raise concern about whether this approach is actually furthering or instead obstructing the advancement of health psychology theories and the quality of health behaviour change interventions. Using examples from theory, the literature and data from previous meta-analyses, these concerns and their implications are explained and illustrated. An iterative protocol for evidence base accumulation is proposed that integrates evidence derived from both experimental and applied behaviour change research, and combines theory development in experimental settings with theory testing in applied real-life settings. As evidence gathered in this manner accumulates, a cumulative science of behaviour change can develop.

  1. Everything should be as simple as possible, but no simpler: towards a protocol for accumulating evidence regarding the active content of health behaviour change interventions

    PubMed Central

    Peters, Gjalt-Jorn Ygram; de Bruin, Marijn; Crutzen, Rik

    2015-01-01

    There is a need to consolidate the evidence base underlying our toolbox of methods of behaviour change. Recent efforts to this effect have conducted meta-regressions on evaluations of behaviour change interventions, deriving each method's effectiveness from its association to intervention effect size. However, there are a range of issues that raise concern about whether this approach is actually furthering or instead obstructing the advancement of health psychology theories and the quality of health behaviour change interventions. Using examples from theory, the literature and data from previous meta-analyses, these concerns and their implications are explained and illustrated. An iterative protocol for evidence base accumulation is proposed that integrates evidence derived from both experimental and applied behaviour change research, and combines theory development in experimental settings with theory testing in applied real-life settings. As evidence gathered in this manner accumulates, a cumulative science of behaviour change can develop. PMID:25793484

  2. Prayer in Clinical Practice: what does evidence support?

    PubMed

    Kim-Godwin, YeounSoo

    2013-01-01

    A Korean-born U.S. nurse educator shares a perspective on prayer in clinical settings in South Korea and asks what appropriate, ethical prayer practice should be in the United States. A review of research on prayer for health and in nursing practice is offered, concluding with evidence-based suggestions for prayer with and for patients in clinical settings.

  3. Applying evidence-based surgery in daily clinical routine: a feasibility study.

    PubMed

    Krahn, Jan; Sauerland, Stefan; Rixen, Dieter; Gregor, Sven; Bouillon, Bertil; Neugebauer, Edmund A M

    2006-03-01

    Although the word evidence-based medicine (EBM) has gained wide popularity, only a few studies have evaluated how EBM works in clinical practice. We have prospectively evaluated the feasibility of evidence-based trauma surgery. Orthopaedic trauma surgeons were asked to produce clinical questions related to the treatment of current patients. An informaticist searched the literature (Medline, Cochrane Library, practice guidelines and textbooks) and reported the findings on every following day. The study's main endpoints were the rate of questions for which relevant evidence (>level V) was available and the time necessary to find and critically appraise medical evidence. In total, 44 EBM questions were formulated, mainly concerning treatment options. PubMed was searched for 39 questions, textbooks for 14, the Cochrane Library for 11, online guidelines for 9 and other sources were used for 4 questions. On average, 157 text items (three per questions) were identified as potentially relevant. Journal articles predominated (83%) over textbooks (10%). Sixty-eight percent of the questions (30 of 44) were answered, either on the basis level 1 (n=13 questions), level 2 (n=6), or level 4 evidence (n=14). Trying to answer a question required 53 min on average, split up between 39 min of database searches and 25 min of obtaining full text articles. In four cases, the evidence suggested a change in clinical management. The physicians were very appreciative of our project and found the provided evidence very helpful for their clinical decisions. Time will be the main barrier against the introduction of clinical EBM. It is likely that clinicians reduce EBM to those situations where evidence is likely to be found. Although the impact of EBM on patient-care was limited, the concept of EBM was successfully implemented.

  4. Evidence-based dental practice: part I. Formulating clinical questions and searching for answers.

    PubMed

    Adeyemo, W L; Akinwande, J A; Bamgbose, B O

    2007-01-01

    Evidence-based dentistry (EBD) is an approach to oral health care that requires the judicious integration of systematic assessments of clinically relevant scientific evidence, relating to the patient's oral and medical condition and history, with the dentist's clinical expertise and the patient's treatment needs and preferences. Evidence-based care is now regarded as the "gold standard" in health care delivery worldwide. EBD involves tracking down the available evidence, assessing its validity and relevance, and then using the "best" evidence to inform decisions regarding care. Although, the concept of evidence-based dentistry is not new, however, anecdotal evidence suggests that the awareness of this concept among Nigerian dental practitioners is low. This first of three articles on evidence-based dental practice discusses the historical background of evidence-based medicine/evidence-based dentistry, how to formulate clear clinical questions and how to track down (search) the available evidence in the literature databases.

  5. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  6. Clinical use of Skype: a review of the evidence base.

    PubMed

    Armfield, Nigel R; Gray, Leonard C; Smith, Anthony C

    2012-04-01

    Skype is a popular and free software application that allows PCs and mobile devices to be used for video communication over the Internet. We reviewed the literature to determine whether the clinical use of Skype is supported by evidence. One small (n = 7) controlled clinical trial had assessed the effect of nursing communication using Skype on elderly patients with dementia and their carers. However, we were unable to identify any large, well-designed studies which had formally evaluated the safety, clinical effectiveness, security and privacy of Skype for the routine delivery of patient care. While there were many case reports and small studies, no firm evidence either in favour of, or against the use of Skype for clinical telehealth was found. The risks and benefits of using Skype for clinical purposes are not known.

  7. Evidence-based medicine, clinical practice guidelines, and common sense in the management of osteoporosis.

    PubMed

    Lewiecki, E Michael; Binkley, Neil

    2009-01-01

    To evaluate the benefits and limitations of randomized controlled trials (RCTs), clinical practice guidelines (CPGs), and clinical judgment in the management of osteoporosis. A review was conducted of the English-language literature on the origins and applications of RCTs, CPGs, evidence-based medicine, and clinical judgment in the management of osteoporosis. Evidence-based medicine is use of the currently available best evidence in making clinical decisions for individual patients. CPGs are recommendations for making clinical decisions based on research evidence, sometimes with consideration of expert opinion, health care policy, and costs of care. The highest levels of medical evidence are usually thought to be RCTs and meta-analyses of high-quality RCTs. Although it is desirable and appropriate for clinicians to consider research evidence from RCTs and recommendations presented in CPGs in making clinical decisions, other factors-such as patient preference, comorbidities, affordability, and availability of care-are important for the actual implementation of evidence-based medicine. Decisions about who to treat, which drug to use, how best to monitor, and how long to treat require clinical skills in addition to knowledge of medical research. The necessity of integrating common sense and clinical judgment is highlighted by the fact that many patients treated for osteoporosis in clinical practice would not qualify for participation in the pivotal clinical trials that demonstrated efficacy and safety of the drugs used to treat them.

  8. The NOTCH3 score: a pre-clinical CADASIL biomarker in a novel human genomic NOTCH3 transgenic mouse model with early progressive vascular NOTCH3 accumulation.

    PubMed

    Rutten, Julie W; Klever, Roselin R; Hegeman, Ingrid M; Poole, Dana S; Dauwerse, Hans G; Broos, Ludo A M; Breukel, Cor; Aartsma-Rus, Annemieke M; Verbeek, J Sjef; van der Weerd, Louise; van Duinen, Sjoerd G; van den Maagdenberg, Arn M J M; Lesnik Oberstein, Saskia A J

    2015-12-29

    CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, leading to toxic NOTCH3 protein accumulation in the small- to medium sized arterioles. The accumulation is systemic but most pronounced in the brain vasculature where it leads to clinical symptoms of recurrent stroke and dementia. There is no therapy for CADASIL, and therapeutic development is hampered by a lack of feasible clinical outcome measures and biomarkers, both in mouse models and in CADASIL patients. To facilitate pre-clinical therapeutic interventions for CADASIL, we aimed to develop a novel, translational CADASIL mouse model. We generated transgenic mice in which we overexpressed the full length human NOTCH3 gene from a genomic construct with the archetypal c.544C > T, p.Arg182Cys mutation. The four mutant strains we generated have respective human NOTCH3 RNA expression levels of 100, 150, 200 and 350 % relative to endogenous mouse Notch3 RNA expression. Immunohistochemistry on brain sections shows characteristic vascular human NOTCH3 accumulation in all four mutant strains, with human NOTCH3 RNA expression levels correlating with age at onset and progression of NOTCH3 accumulation. This finding was the basis for developing the 'NOTCH3 score', a quantitative measure for the NOTCH3 accumulation load. This score proved to be a robust and sensitive method to assess the progression of NOTCH3 accumulation, and a feasible biomarker for pre-clinical therapeutic testing. This novel, translational CADASIL mouse model is a suitable model for pre-clinical testing of therapeutic strategies aimed at delaying or reversing NOTCH3 accumulation, using the NOTCH3 score as a biomarker.

  9. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

  10. Evidence of the clinical effectiveness of cognitive pharmaceutical services for aged patients.

    PubMed

    Sáez-Benito, Loreto; Fernandez-Llimos, Fernando; Feletto, Eleonora; Gastelurrutia, Miguel Angel; Martinez-Martinez, Fernando; Benrimoj, Shalom I

    2013-07-01

    cognitive pharmaceutical services (CPSs) encompass a variety of pharmacists' interventions to optimise pharmacotherapy. The clinical effectiveness of CPSs for aged patients remains controversial. to analyse and describe the evidence of the clinical effectiveness of CPSs in aged patients by means of performing a systematic review of systematic reviews. using the recommended methodology by Cochrane, a search was undertaken for systematic reviews of the clinical effectiveness of CPSs in MEDLINE, EMBASE, DOAJ, SCIELO and COCHRANE LIBRARY. Reviews were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) instrument. Quality of the evidence in the reviews was ranked using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. a total of 14 systematic reviews and one meta-analysis were analysed. The overall quality of the reviews was moderate. High and moderate strength of evidence was found for the positive effect of certain CPSs on reducing the number and improving the appropriateness of medicines. There was conflicting evidence of the effect on adherence. There was limited evidence of high and moderate strength on clinical outcomes. No positive evidence was found on mortality, hospitalisations, functional capacity and cognitive function. No systematic reviews reported the effect on the level of control of health problems. certain types of CPSs reduce the number of medicines and improve the appropriateness of prescriptions. Longer follow-up periods and/or the use of surrogate clinical variables measuring the short-term impact are required to demonstrate the effect on clinical outcomes.

  11. Application of evidence-based dentistry: from research to clinical periodontal practice.

    PubMed

    Kwok, Vivien; Caton, Jack G; Polson, Alan M; Hunter, Paul G

    2012-06-01

    Dentists need to make daily decisions regarding patient care, and these decisions should essentially be scientifically sound. Evidence-based dentistry is meant to empower clinicians to provide the most contemporary treatment. The benefits of applying the evidence-based method in clinical practice include application of the most updated treatment and stronger reasoning to justify the treatment. A vast amount of information is readily accessible with today's digital technology, and a standardized search protocol can be developed to ensure that a literature search is valid, specific and repeatable. It involves developing a preset question (population, intervention, comparison and outcome; PICO) and search protocol. It is usually used academically to perform commissioned reviews, but it can also be applied to answer simple clinical queries. The scientific evidence thus obtained can then be considered along with patient preferences and values, clinical patient circumstances and the practitioner's experience and judgment in order to make the treatment decision. This paper describes how clinicians can incorporate evidence-based methods into patient care and presents a clinical example to illustrate the process. © 2012 John Wiley & Sons A/S.

  12. Using Time-Varying Evidence to Test Models of Decision Dynamics: Bounded Diffusion vs. the Leaky Competing Accumulator Model

    PubMed Central

    Tsetsos, Konstantinos; Gao, Juan; McClelland, James L.; Usher, Marius

    2012-01-01

    When people make decisions, do they give equal weight to evidence arriving at different times? A recent study (Kiani et al., 2008) using brief motion pulses (superimposed on a random moving dot display) reported a primacy effect: pulses presented early in a motion observation period had a stronger impact than pulses presented later. This observation was interpreted as supporting the bounded diffusion (BD) model and ruling out models in which evidence accumulation is subject to leakage or decay of early-arriving information. We use motion pulses and other manipulations of the timing of the perceptual evidence in new experiments and simulations that support the leaky competing accumulator (LCA) model as an alternative to the BD model. While the LCA does include leakage, we show that it can exhibit primacy as a result of competition between alternatives (implemented via mutual inhibition), when the inhibition is strong relative to the leak. Our experiments replicate the primacy effect when participants must be prepared to respond quickly at the end of a motion observation period. With less time pressure, however, the primacy effect is much weaker. For 2 (out of 10) participants, a primacy bias observed in trials where the motion observation period is short becomes weaker or reverses (becoming a recency effect) as the observation period lengthens. Our simulation studies show that primacy is equally consistent with the LCA or with BD. The transition from primacy-to-recency can also be captured by the LCA but not by BD. Individual differences and relations between the LCA and other models are discussed. PMID:22701399

  13. Traditional chinese medicine: an update on clinical evidence.

    PubMed

    Xue, Charlie C L; Zhang, Anthony L; Greenwood, Kenneth M; Lin, Vivian; Story, David F

    2010-03-01

    As an alternative medical system, Traditional Chinese Medicine (TCM) has been increasingly used over the last several decades. Such a consumer-driven development has resulted in introduction of education programs for practitioner training, development of product and practitioner regulation systems, and generation of an increasing interest in research. Significant efforts have been made in validating the quality, effectiveness, and safety of TCM interventions evidenced by a growing number of published trials and systematic reviews. Commonly, the results of these studies were inconclusive due to the lack of quality and quantity of the trials to answer specific and answerable clinical questions. The methodology of a randomized clinical trial (RCT) is not free from bias, and the unique features of TCM (such as individualization and holism) further complicate effective execution of RCTs in TCM therapies. Thus, data from limited RCTs and systematic reviews need to be interpreted with great caution. Nevertheless, until new and specific methodology is developed that can adequately address these methodology challenges for RCTs in TCM, evidence from quality RCTs and systematic reviews still holds the credibility of TCM in the scientific community. This article summarizes studies on TCM utilization, and regulatory and educational development with a focus on updating the TCM clinical evidence from RCTs and systematic reviews over the last decade. The key issues and challenges associated with evidence-based TCM developments are also explored.

  14. Integrating clinical and economic evidence in clinical guidelines: More needed than ever!

    PubMed

    Knies, Saskia; Severens, Johan L; Brouwer, Werner B F

    2018-04-26

    In recent years, several expensive new health technologies have been introduced. The availability of those technologies intensifies the discussion regarding the affordability of these technologies at different decision-making levels. On the meso level, both hospitals and clinicians are facing budget constraints resulting in a tension to balance between different patients' interests. As such, it is crucial to make optimal use of the available resources. Different strategies are in place to deal with this problem, but decisions on a macro level on what to fund or not can limit the role and freedom of clinicians in their decisions on a micro level. At the same time, without central guidance regarding such decisions, micro level decisions may lead to inequities and undesirable treatment variation between clinicians and hospitals. The challenge is to find instruments that can balance both levels of decision making. Clinicians are becoming increasingly aware that their decisions to spend more resources (like time and budget) on 1 particular patient group reduce the resources available to other patients. Involving clinicians in thinking about the optimal use of limited resources, also in an attempt to bridge the world of economic reasoning and clinical practice, is crucial therefore. We argue that clinical guidelines may prove a clear vehicle for this by including both clinical and economic evidence to support the recommendations made. The development of such guidelines requires cooperation of clinicians, and health economists are cooperating with each other. The development of clinical guidelines which combine economic and clinical evidence should be stimulated, to balance central guidance and uniformity while maintaining necessary decentralized freedom. This is an opportunity to combine the reality of budgets and opportunity costs with clinical practice. Missing this opportunity risks either variation and inequity or central and necessarily crude measures. © 2018 The

  15. Efficacy of an evidence-based clinical decision support in primary care practices: a randomized clinical trial.

    PubMed

    McGinn, Thomas G; McCullagh, Lauren; Kannry, Joseph; Knaus, Megan; Sofianou, Anastasia; Wisnivesky, Juan P; Mann, Devin M

    2013-09-23

    There is consensus that incorporating clinical decision support into electronic health records will improve quality of care, contain costs, and reduce overtreatment, but this potential has yet to be demonstrated in clinical trials. To assess the influence of a customized evidence-based clinical decision support tool on the management of respiratory tract infections and on the effectiveness of integrating evidence at the point of care. In a randomized clinical trial, we implemented 2 well-validated integrated clinical prediction rules, namely, the Walsh rule for streptococcal pharyngitis and the Heckerling rule for pneumonia. INTERVENTIONS AND MAIN OUTCOMES AND MEASURES: The intervention group had access to the integrated clinical prediction rule tool and chose whether to complete risk score calculators, order medications, and generate progress notes to assist with complex decision making at the point of care. The intervention group completed the integrated clinical prediction rule tool in 57.5% of visits. Providers in the intervention group were significantly less likely to order antibiotics than the control group (age-adjusted relative risk, 0.74; 95% CI, 0.60-0.92). The absolute risk of the intervention was 9.2%, and the number needed to treat was 10.8. The intervention group was significantly less likely to order rapid streptococcal tests compared with the control group (relative risk, 0.75; 95% CI, 0.58-0.97; P= .03). The integrated clinical prediction rule process for integrating complex evidence-based clinical decision report tools is of relevant importance for national initiatives, such as Meaningful Use. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01386047.

  16. Evidence Does Not Support Clinical Screening of Literacy

    PubMed Central

    Wolf, Michael S.

    2007-01-01

    Limited health literacy is a significant risk factor for adverse health outcomes. Despite controversy, many health care professionals have called for routine clinical screening of patients’ literacy skills. Whereas brief literacy screening tools exist that with further evaluation could potentially be used to detect limited literacy in clinical settings, no screening program for limited literacy has been shown to be effective. Yet there is a noted potential for harm, in the form of shame and alienation, which might be induced through clinical screening. There is fair evidence to suggest that possible harm outweighs any current benefits; therefore, clinical screening for literacy should not be recommended at this time. PMID:17992564

  17. Evidence accumulation in decision making: unifying the "take the best" and the "rational" models.

    PubMed

    Lee, Michael D; Cummins, Tarrant D R

    2004-04-01

    An evidence accumulation model of forced-choice decision making is proposed to unify the fast and frugal take the best (TTB) model and the alternative rational (RAT) model with which it is usually contrasted. The basic idea is to treat the TTB model as a sequential-sampling process that terminates as soon as any evidence in favor of a decision is found and the rational approach as a sequential-sampling process that terminates only when all available information has been assessed. The unified TTB and RAT models were tested in an experiment in which participants learned to make correct judgments for a set of real-world stimuli on the basis of feedback, and were then asked to make additional judgments without feedback for cases in which the TTB and the rational models made different predictions. The results show that, in both experiments, there was strong intraparticipant consistency in the use of either the TTB or the rational model but large interparticipant differences in which model was used. The unified model is shown to be able to capture the differences in decision making across participants in an interpretable way and is preferred by the minimum description length model selection criterion.

  18. Integrating evidence-based practice into RN-to-BSN clinical nursing education.

    PubMed

    Oh, Eui Geum; Kim, Sunah; Kim, So Sun; Kim, Sue; Cho, Eun Yong; Yoo, Ji-Soo; Kim, Hee Soon; Lee, Ju Hee; You, Mi Ae; Lee, Hyejung

    2010-07-01

    This study examines the effects of integrating evidence-based practice (EBP) into clinical practicum on EBP efficacy and barriers to research utilization among Korean RN-to-BSN students. A one-group pretest-posttest design was used. Eighty-one students were recruited from a school of nursing in Korea. Evidence-based practice clinical practicum was composed of two consecutive programs during one semester. Lectures, individual mentoring on EBP practicum, small group, and wrap-up conferences were provided. Outcomes of EBP efficacy and barriers to research utilization were analyzed using paired t tests for 74 final participants. Evidence-based practice efficacy scores increased significantly (p < 0.05), and the barriers to research utilization scores decreased significantly after the EBP clinical practicum. The results highlight the effectiveness of EBP education among RN-to-BSN students. These results may help health educators develop effective educational strategies to integrate EBP concepts into a clinical practicum. Copyright 2010, SLACK Incorporated.

  19. Memory Accumulation Mechanisms in Human Cortex Are Independent of Motor Intentions

    PubMed Central

    Tosoni, Annalisa; Mignogna, Valeria; McAvoy, Mark P.; Shulman, Gordon L.; Corbetta, Maurizio; Romani, Gian Luca

    2014-01-01

    Previous studies on perceptual decision-making have often emphasized a tight link between decisions and motor intentions. Human decisions, however, also depend on memories or experiences that are not closely tied to specific motor responses. Recent neuroimaging findings have suggested that, during episodic retrieval, parietal activity reflects the accumulation of evidence for memory decisions. It is currently unknown, however, whether these evidence accumulation signals are functionally linked to signals for motor intentions coded in frontoparietal regions and whether activity in the putative memory accumulator tracks the amount of evidence for only previous experience, as reflected in “old” reports, or for both old and new decisions, as reflected in the accuracy of memory judgments. Here, human participants used saccadic-eye and hand-pointing movements to report recognition judgments on pictures defined by different degrees of evidence for old or new decisions. A set of cortical regions, including the middle intraparietal sulcus, showed a monotonic variation of the fMRI BOLD signal that scaled with perceived memory strength (older > newer), compatible with an asymmetrical memory accumulator. Another set, including the hippocampus and the angular gyrus, showed a nonmonotonic response profile tracking memory accuracy (higher > lower evidence), compatible with a symmetrical accumulator. In contrast, eye and hand effector-specific regions in frontoparietal cortex tracked motor intentions but were not modulated by the amount of evidence for the effector outcome. We conclude that item recognition decisions are supported by a combination of symmetrical and asymmetrical accumulation signals largely segregated from motor intentions. PMID:24828652

  20. Accumulating Evidence for a Drug–Drug Interaction Between Methotrexate and Proton Pump Inhibitors

    PubMed Central

    Mackey, Ann Corken; Kluetz, Paul; Jappar, Dilara; Korvick, Joyce

    2012-01-01

    Background. A number of medications are known to interact with methotrexate through various mechanisms. The aim of this article is to apprise practitioners of a new labeling change based on the accumulating evidence for a possible drug–drug interaction between methotrexate (primarily at high doses) and proton pump inhibitors (PPIs). Methods. The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database of spontaneous adverse event reports and the published literature were searched for cases reporting an interaction between methotrexate and PPIs. Results. A search of the AERS database and existing literature found several individual case reports of drug–drug interactions and three additional supportive studies that suggest potential underlying mechanisms for the interaction. Conclusion. There is evidence to suggest that concomitant use of methotrexate (primarily at high doses) with PPIs such as omeprazole, esomeprazole, and pantoprazole may decrease methotrexate clearance, leading to elevated serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. In several case reports, no methotrexate toxicity was found when a histamine H2 blocker was substituted for a PPI. Based on the reviewed data, the FDA updated the methotrexate label to include the possible drug–drug interaction between high-dose methotrexate and PPIs. Physicians should be alerted to this potential drug–drug interaction in patients receiving concomitant high-dose methotrexate and PPIs. PMID:22477728

  1. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in vivo bioavailability data with an acute pharmacological effect or clinical evidence of safety and...

  2. Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection.

    PubMed

    Mentzer, Robert M; Lasley, Robert D; Jessel, Andreas; Karmazyn, Morris

    2003-02-01

    Although the mechanisms underlying ischemia/reperfusion injury remain elusive, evidence supports the etiologic role of intracellular calcium overload and oxidative stress induced by reactive oxygen species. Activation of the sodium hydrogen exchanger (NHE) is associated with intracellular calcium accumulation. Inhibition of the NHE-1 isoform may attenuate the consequences of this injury. Although there is strong preclinical and early clinical evidence that NHE inhibitors may be cardioprotective, definitive proof of this concept in humans awaits the results of ongoing clinical trials.

  3. Ultrasound enhanced thrombolysis: Clinical evidence

    NASA Astrophysics Data System (ADS)

    Alexandrov, Andrei V.

    2005-04-01

    Phase II CLOTBUST randomized clinical trial (Houston, Barcelona, Edmonton, Calgary) evaluated patients with acute ischemic stroke due to intracranial occlusion and treated with intravenous tissue plasminogen activator (TPA) within 3 h of symptom onset. Randomization: monitoring with pulsed wave 2 MHz transcranial Doppler (TCD) (Target) or placebo monitoring (Control). Safety: symptomatic bleeding to the brain (sICH). Primary end-point: complete recanalization on TCD or dramatic clinical recovery by the total NIHSS score <3, or improvement by >10 NIHSS points within 2 hours after TPA bolus. All projected 126 patients were randomized 1:1 to target (median NIHSS 16) or control (NIHSS 17). sICH: 4.8% Target, 4.8% Controls. Primary end-point was achieved by 31 (49%, Target) versus 19 (30%, Control), p<0.03. At 3 months, 22 (42% Target) and 14 (29% Control) patients achieved favorable outcomes. Continuous TCD monitoring of intracranial occlusion safely augments TPA-induced arterial recanalization, and 2 MHz diagnostic ultrasound has a positive biological activity that aids systemic thrombolytic therapy. For the first time in clinical medicine, the CLOTBUST trial provides the evidence that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming intense multi-disciplinary experimental research conducted worldwide for the past 30 years.

  4. Evidence-based Medicine in Pediatric Orthopaedics: Evidence-based Practice Committee Summary of Levels of Evidence, Clinical Practice Guidelines, Appropriate Use Criteria, and Best Practice Guidelines.

    PubMed

    Gandhi, Jigar S; Shea, Kevin G; Sponseller, Paul D; Brighton, Brian K; Ganley, Theodore J

    2018-04-30

    The concept of evidence-based medicine has evolved over the past 2 decades, and has become a cornerstone to clinical decision-making in virtually every aspect of medicine. With a commitment to providing its members with high-quality evidence-based guidelines, the American Academy of Orthopaedic Surgeons has instituted concerted efforts since 2006 to develop clinical practice guidelines (CPGs) and appropriate use criteria (AUCs) for certain orthopaedic conditions. Many of these CPGs and AUCs detail the management of pediatric orthopaedic conditions. By the same token, members of the Pediatric Orthopaedic Society of North America (POSNA) Evidence Based Practice Committee have been publishing succinct evaluations of randomized controlled trials in pediatric orthopaedic surgery to create an evidence-based repository for quick reference to available high-level evidence as well as resource to identify gaps in the current research and identify opportunities for future investigation. In instances where higher-level evidence needed to develop CPGs is not available to address a critically important clinical question, consensus recommendations from experts in the field have been obtained to develop best practice guidelines (BPGs). The purpose of this review is to provide readers with a deeper understanding of the key principles of evidence-based medicine and methodologies used for the development of CPGs, AUCs, and BPGs.

  5. [Titanium or steel as osteosynthesis material : Systematic literature search for clinical evidence].

    PubMed

    Joeris, Alexander; Goldhahn, Sabine; Rometsch, Elke; Höntzsch, Dankward

    2017-02-01

    The selection of the appropriate implant material, stainless steel or titanium, is still the decision of the surgeon and/or the affiliated institution. Additionally, remarkable international differences can be found between the different markets, which cannot really be explained. A systematic literature search was performed to verify whether there is clinical evidence for the preference of one material over the other. The systematic literature search was performed utilizing the internet databases PubMed, Cochrane and Web of Science. Comparative studies were included that reported on adult patients with osteosynthesis of extremities after trauma using either stainless steel or titanium implants. Information was extracted about infection rates, incidence of clinically relevant allergies, problems with implant removal and other complications. A total of 18 publications were identified to be eligible and 2 referenced articles were added. In summary, there is insufficient clinical evidence that the use of titanium or steel implants has a positive or negative effect on fracture healing, shows different rates of allergies, different rates of infections or mechanical failure. No supporting evidence could be identified for the difficulties with removal of titanium implants reported by surgeons. This systematic literature search did not provide any clinical evidence for material-related differences between titanium or stainless steel implants for fracture fixation. Based on the current clinical evidence both titanium and steel implants can be considered to be of equal value. The reported difficulties with implant removal are not reflected in the published literature.

  6. Analysis of evidence within the AUA's clinical practice guidelines.

    PubMed

    Antoine, Samuel G; Small, Alexander C; McKiernan, James M; Shah, Ojas

    2018-02-01

    Surgical subspecialty societies release clinical practice guidelines (CPGs) to provide topic-specific recommendations to healthcare providers. We hypothesize that there may be significant differences in statement strength and evidence quality both within the American Urological Association (AUA) guidelines and compared to those published by the American Academy of Orthopedic Surgeons (AAOS) and American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). CPGs issued through 2017 were extracted from the AUAnet.org. Statements were characterized by evidence basis, strength, and evidence quality. CPGs were compared among urologic subspecialties and to those from the AAOS and AAO-HNS. Analysis used Fisher's exact tests and Student's t-tests with significance p < 0.05. A total of 25 AUA CPGs (672 statements) were reviewed and 34.6% were non-evidence based with the highest proportions in pediatrics (47.5%) and sexual medicine (46.5%). The AUA has published over twice as many statements as the AAOS and quadruple that of the AAO-HNS. A smaller proportion of the AUA statements were evidence-based (65.4%) compared to the AAOS (80.5%, p < 0.001) and AAO-HNS (99.8%, p < 0.001), and fewer used "high" quality evidence (AUA 7.2% versus AAOS 21.2%, p < 0.001; versus AAO-HNS 16.1%, p < 0.001). The AUA has published broad CPGs that far exceed those from the AAOS and AAO-HNS. The AUA has utilized extensive resources to provide guidance to help standardize care among urologists. The AAOS and AAO-HNS may not provide guidelines when evidence is limited. With the continued increase of high quality clinical trials, the AUA will be able to continue improving its robust set of evidence-based CPGs.

  7. Predicting the amount of intraperitoneal fluid accumulation by computed tomography and its clinical use in patients with perforated peptic ulcer.

    PubMed

    Ishiguro, Toru; Kumagai, Youichi; Baba, Hiroyuki; Tajima, Yusuke; Imaizumi, Hideko; Suzuki, Okihide; Kuwabara, Koki; Matsuzawa, Takeaki; Sobajima, Jun; Fukuchi, Minoru; Ishibashi, Keiichiro; Mochiki, Erito; Ishida, Hideyuki

    2014-01-01

    The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien-Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications.

  8. Predicting the Amount of Intraperitoneal Fluid Accumulation by Computed Tomography and Its Clinical Use in Patients With Perforated Peptic Ulcer

    PubMed Central

    Ishiguro, Toru; Kumagai, Youichi; Baba, Hiroyuki; Tajima, Yusuke; Imaizumi, Hideko; Suzuki, Okihide; Kuwabara, Koki; Matsuzawa, Takeaki; Sobajima, Jun; Fukuchi, Minoru; Ishibashi, Keiichiro; Mochiki, Erito; Ishida, Hideyuki

    2014-01-01

    The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien–Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications. PMID:25437594

  9. Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline.

    PubMed

    Pottie, Kevin; Thompson, Wade; Davies, Simon; Grenier, Jean; Sadowski, Cheryl A; Welch, Vivian; Holbrook, Anne; Boyd, Cynthia; Swenson, Robert; Ma, Andy; Farrell, Barbara

    2018-05-01

    To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated by conducting a systematic review of BZRA deprescribing trials for insomnia, as well as performing a review of reviews of the harms of continued BZRA use and narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality of evidence ratings were used to generate recommendations. The team refined guideline content and recommendations through consensus and synthesized clinical considerations to address front-line clinician questions. The draft guideline was reviewed by clinicians and stakeholders. We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia. Benzodiazepine receptor agonists are associated with harms

  10. An evidence-based approach to the management of low back pain and sciatica: how the evidence is applied in clinical cases.

    PubMed

    Goh, L; Bawendi, A; Samanta, J; Samanta, A

    2003-09-01

    Low back pain and sciatica are common complaints that affect a major proportion of the population at some time in their lives. The treatment and management of this condition may vary widely. The present paper aims to provide an evidence-based approach to the management of low back pain and sciatica, and demonstrates how to search for the evidence and how to apply it practically in individual patients. The principles underlying evidence-based medicine are explained. The practice of evidence-based medicine requires initial formulation of the appropriate clinical question, followed by searching databases for relevant evidence. Finally evidence needs to be applied on a patient-specific basis. Best Evidence, the Cochrane Library, Embase and Medline were searched to obtain quality controlled information regarding the management of low back pain and sciatica. Current evidence shows that an active exercise programme promotes early recovery. This may allow patients to resume an active and sportive lifestyle. Epidural corticosteroid injections may help to resolve additional troublesome symptoms of sciatica. Two clinical cases are used to show how evidence-based medicine can be individualized to specific patients. A patient-focused strategy combining best evidence and clinical expertise is suggested as the mainstay for the management of low back pain.

  11. A Growing Consensus for Change in Interpretation of Clinical Research Evidence.

    PubMed

    Wilkerson, Gary B; Denegar, Craig R

    2018-03-01

      The paradigm of evidence-based practice (EBP) is well established among the health care professions, but perspectives on the best methods for acquiring, analyzing, appraising, and using research evidence are evolving.   The EBP paradigm has shifted away from a hierarchy of research-evidence quality to recognize that multiple research methods can yield evidence to guide clinicians and patients through a decision-making process. Whereas the "frequentist" approach to data interpretation through hypothesis testing has been the dominant analytical method used by and taught to athletic training students and scholars, this approach is not optimal for integrating evidence into routine clinical practice. Moreover, the dichotomy of rejecting, or failing to reject, a null hypothesis is inconsistent with the Bayesian-like clinical decision-making process that skilled health care providers intuitively use. We propose that data derived from multiple research methods can be best interpreted by reporting a credible lower limit that represents the smallest treatment effect at a specified level of certainty, which should be judged in relation to the smallest effect considered to be clinically meaningful. Such an approach can provide a quantifiable estimate of certainty that an individual patient needs follow-up attention to prevent an adverse outcome or that a meaningful level of therapeutic benefit will be derived from a given intervention.   The practice of athletic training will be influenced by the evolution of the EBP paradigm. Contemporary practice will require clinicians to expand their critical-appraisal skills to effectively integrate the results derived from clinical research into the care of individual patients. Proper interpretation of a credible lower limit value for a magnitude ratio has the potential to increase the likelihood of favorable patient outcomes, thereby advancing the practice of evidence-based athletic training.

  12. Evidence-based clinical guidelines in Kyrgyz Republic.

    PubMed

    Zurdinova, A A

    2015-01-01

    Improving quality of care in many countries is one of the priorities of health systems. At the same time one of the most important methods of improving quality of care is the widespread use of methods and principles of evidence-based medicine (EBM) [1]. The implementation of EBM in public health practice provides for the optimization of quality of care in terms of safety, efficacy and cost, one way of which is the use of clinical guidelines. Clinical guidelines developed with the use of EBM, provide an opportunity to use the latest and accurate information to optimize or neutralize impact on physician decision-making of subjective factors such as intuition, expertise, opinion of respected colleagues, recommendations of popular manuals and handbooks, etc. To assess and analyze the developed clinical guidelines (CG) and protocols (CP) in the Kyrgyz Republic in the period from 2008 to 2014 and evaluate their implementation in practical healthcare. Retrospective analysis of the developed clinical guidelines and protocols according to the approved methodology, interviewing leaders, questioning doctors and patients for their implementation. All participants gave informed consent for voluntary participation in the study. Within the framework of the National Program "Manas Taalimi" "Strategy for development of evidence-based medicine in the Kyrgyz Republic for 2006-2010" (MOH Order №490 from 09.04.06) was developed and approved for use. Its main purpose was to create a sustainable system of development, deployment and monitoring of the CG and CP and further promotion of EBM into practical health care, education and science. As a result, a number of documents ("Expert Council for assessing the quality of clinical guidelines/protocols", "AGREE instrument to assess the methodological content of clinical guidelines" [2], "The methodology of development and adaptation of clinical guidelines based on evidence-based medicine") were approved by the Order of the Ministry of

  13. An evidence-based clinical guideline for the use of antithrombotic therapies in spine surgery.

    PubMed

    Bono, Christopher M; Watters, William C; Heggeness, Michael H; Resnick, Daniel K; Shaffer, William O; Baisden, Jamie; Ben-Galim, Peleg; Easa, John E; Fernand, Robert; Lamer, Tim; Matz, Paul G; Mendel, Richard C; Patel, Rajeev K; Reitman, Charles A; Toton, John F

    2009-12-01

    The objective of the North American Spine Society (NASS) Evidence-Based Clinical Guideline on antithrombotic therapies in spine surgery was to provide evidence-based recommendations to address key clinical questions surrounding the use of antithrombotic therapies in spine surgery. The guideline is intended to address these questions based on the highest quality clinical literature available on this subject as of February 2008. The goal of the guideline recommendations was to assist in delivering optimum, efficacious treatment with the goal of preventing thromboembolic events. To provide an evidence-based, educational tool to assist spine surgeons in minimizing the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Systematic review and evidence-based clinical guideline. This report is from the Antithrombotic Therapies Work Group of the NASS Evidence-Based Guideline Development Committee. The work group was composed of multidisciplinary spine care specialists, all of whom were trained in the principles of evidence-based analysis. Each member of the group was involved in formatting a series of clinical questions to be addressed by the group. The final questions agreed on by the group are the subject of this report. A literature search addressing each question and using a specific search protocol was performed on English language references found in MEDLINE, EMBASE (Drugs and Pharmacology), and four additional, evidence-based databases. The relevant literature was then independently rated by at least three reviewers using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final grades of recommendation for the answers to each clinical question were arrived at via Web casts among members of the work group using standardized grades of recommendation. When Level I to IV evidence was insufficient to support a recommendation to answer a specific clinical question, expert consensus was arrived at by

  14. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, A.; Divsalar, D.; Yao, K.

    2004-01-01

    In this paper we propose an innovative channel coding scheme called Accumulate Repeat Accumulate codes. This class of codes can be viewed as trubo-like codes, namely a double serial concatenation of a rate-1 accumulator as an outer code, a regular or irregular repetition as a middle code, and a punctured accumulator as an inner code.

  15. Clinical and Research Perspectives on Nonspeech Oral Motor Treatments and Evidence-Based Practice

    ERIC Educational Resources Information Center

    Muttiah, Nimisha; Georges, Katie; Brackenbury, Tim

    2011-01-01

    Purpose: Evidence-based practice (EBP) involves the incorporation of research evidence, clinical expertise, and client values in clinical decision making. One case in which these factors conflict is the use of nonspeech oral motor treatments (NSOMTs) for children with developmental speech sound disorders. Critical reviews of the research evidence…

  16. Emollient treatment of atopic dermatitis: latest evidence and clinical considerations

    PubMed Central

    Kung, Jeng Sum Charmaine; Ng, Wing Gi Gigi; Leung, Ting Fan

    2018-01-01

    Aim To review current classes of emollients in the market, their clinical efficacy in atopic dermatitis (AD) and considerations for choice of an emollient. Methods PubMed Clinical Queries under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews were used as the search engine. Keywords of ‘emollient or moisturizer’ and ‘atopic dermatitis’ were used. Overview of findings Using the keywords of ‘emollient’ and ‘atopic dermatitis’, there were 105 and 36 hits under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews, respectively. Plant-derived products, animal products and special ingredients were discussed. Selected proprietary products were tabulated. Conclusions A number of proprietary emollients have undergone trials with clinical data available on PubMed-indexed journals. Most moisturizers showed some beneficial effects, but there was generally no evidence that one moisturizer is superior to another. Choosing an appropriate emollient for AD patients would improve acceptability and adherence for emollient treatment. Physician’s recommendation is the primary consideration for patients when selecting a moisturizer/emollient; therefore, doctors should provide evidence-based information about these emollients. PMID:29692852

  17. The impact of clinical nurse specialists on clinical pathways in the application of evidence-based practice.

    PubMed

    Gurzick, Martha; Kesten, Karen S

    2010-01-01

    The purpose of this article was to address the call for evidence-based practice through the development of clinical pathways and to assert the role of the clinical nurse specialist (CNS) as a champion in clinical pathway implementation. In the current health care system, providing quality of care while maintaining cost-effectiveness is an ever-growing battle that institutions face. The CNS's role is central to meeting these demands. An extensive literature review has been conducted to validate the use of clinical pathways as a means of improving patient outcomes. This literature also suggests that clinical pathways must be developed, implemented, and evaluated utilizing validated methods including the use of best practice standards. Execution of clinical pathways should include a clinical expert, who has the ability to look at the system as a whole and can facilitate learning and change by employing a multitude of competencies while maintaining a sphere of influence over patient and families, nurses, and the system. The CNS plays a pivotal role in influencing effective clinical pathway development, implementation, utilization, and ongoing evaluation to ensure improved patient outcomes and reduced costs. This article expands upon the call for evidence-based practice through the utilization of clinical pathways to improve patient outcomes and reduce costs and stresses the importance of the CNS as a primary figure for ensuring proper pathway development, implementation, and ongoing evaluation. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Clinical evidence for orphan medicinal products-a cause for concern?

    PubMed

    Picavet, Eline; Cassiman, David; Hollak, Carla E; Maertens, Johan A; Simoens, Steven

    2013-10-16

    The difficulties associated with organising clinical studies for orphan medicinal products (OMPs) are plentiful. Recent debate on the long-term effectiveness of some OMPs, led us to question whether the initial standards for clinical evidence for OMPs, set by the European Medicines Agency (EMA) at the time of marketing authorization, are too low. Therefore, the aim of this study was to quantitatively evaluate the characteristics and quality of clinical evidence that is presented for OMPs to obtain marketing authorization in Europe, using the new and validated COMPASS tool. We quantitatively assessed the characteristics and quality of clinical evidence of the pivotal studies of 64 OMPs as described in the European Public Assessment Report and/or the Scientific Discussion document prepared by the Committee for Human Medicinal Products of the EMA. The 64 OMPs were altogether authorized for 78 orphan indications, for which 117 studies were identified as 'pivotal' or 'main' studies. In approximately two thirds of the studies, the allocation was randomized (64.8%) and a control arm was used (68.5%). Half of the studies applied some type of blinding. Only a minority (26.9%) of the studies included a Quality-of-Life (QoL) related endpoint, of which a third claim an improvement in QoL. Upon analyzing the quality of reporting, we found that some aspects (i.e. the endpoints, the sampling criteria, and the interventions) are well described, whereas other items (i.e. a description of the patients and of potential biases) are not reported for all studies. In conclusion, the pivotal studies that are the basis for marketing authorization of OMPs are a cause for concern, as they exhibit methodological flaws i.e. the lack of QoL-related endpoints as outcome, lack of blinding in the study design and the use of surrogate endpoints. Additionally, there are shortcomings in the reporting of those studies that complicate the interpretation. A more demanding regulatory process for OMPs is

  19. Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice.

    PubMed

    Beyer-Westendorf, Jan; Camm, A John; Coleman, Craig I; Tamayo, Sally

    2016-09-28

    Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.

  20. Enhancing clinical evidence by proactively building quality into clinical trials.

    PubMed

    Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

    2016-08-01

    Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the

  1. Type of Evidence Behind Point-of-Care Clinical Information Products: A Bibliometric Analysis

    PubMed Central

    2011-01-01

    Background Point-of-care (POC) products are widely used as information reference tools in the clinical setting. Although usability, scope of coverage, ability to answer clinical questions, and impact on health outcomes have been studied, no comparative analysis of the characteristics of the references, the evidence for the content, in POC products is available. Objective The objective of this study was to compare the type of evidence behind five POC clinical information products. Methods This study is a comparative bibliometric analysis of references cited in monographs in POC products. Five commonly used products served as subjects for the study: ACP PIER, Clinical Evidence, DynaMed, FirstCONSULT, and UpToDate. The four clinical topics examined to identify content in the products were asthma, hypertension, hyperlipidemia, and carbon monoxide poisoning. Four indicators were measured: distribution of citations, type of evidence, product currency, and citation overlap. The type of evidence was determined based primarily on the publication type found in the MEDLINE bibliographic record, as well as the Medical Subject Headings (MeSH), both assigned by the US National Library of Medicine. MeSH is the controlled vocabulary used for indexing articles in MEDLINE/PubMed. Results FirstCONSULT had the greatest proportion of references with higher levels of evidence publication types such as systematic review and randomized controlled trial (137/153, 89.5%), although it contained the lowest total number of references (153/2330, 6.6%). DynaMed had the largest total number of references (1131/2330, 48.5%) and the largest proportion of current (2007-2009) references (170/1131, 15%). The distribution of references cited for each topic varied between products. For example, asthma had the most references listed in DynaMed, Clinical Evidence, and FirstCONSULT, while hypertension had the most references in UpToDate and ACP PIER. An unexpected finding was that the rate of citation

  2. Valerian: no evidence for clinically relevant interactions.

    PubMed

    Kelber, Olaf; Nieber, Karen; Kraft, Karin

    2014-01-01

    In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  3. Valerian: No Evidence for Clinically Relevant Interactions

    PubMed Central

    Nieber, Karen; Kraft, Karin

    2014-01-01

    In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients. PMID:25093031

  4. Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels.

    PubMed

    Wang, Bo; Canestaro, William J; Choudhry, Niteesh K

    2014-12-01

    Genetic biomarkers that predict a drug's efficacy or likelihood of toxicity are assuming increasingly important roles in the personalization of pharmacotherapy, but concern exists that evidence that links use of some biomarkers to clinical benefit is insufficient. Nevertheless, information about the use of biomarkers appears in the labels of many prescription drugs, which may add confusion to the clinical decision-making process. To evaluate the evidence that supports pharmacogenomic biomarker testing in drug labels and how frequently testing is recommended. Publicly available US Food and Drug Administration databases. We identified drug labels that described the use of a biomarker and evaluated whether the label contained or referenced convincing evidence of its clinical validity (ie, the ability to predict phenotype) and clinical utility (ie, the ability to improve clinical outcomes) using guidelines published by the Evaluation of Genomic Applications in Practice and Prevention Working Group. We graded the completeness of the citation of supporting studies and determined whether the label recommended incorporation of biomarker test results in therapeutic decision making. Of the 119 drug-biomarker combinations, only 43 (36.1%) had labels that provided convincing clinical validity evidence, whereas 18 (15.1%) provided convincing evidence of clinical utility. Sixty-one labels (51.3%) made recommendations about how clinical decisions should be based on the results of a biomarker test; 36 (30.3%) of these contained convincing clinical utility data. A full description of supporting studies was included in 13 labels (10.9%). Fewer than one-sixth of drug labels contained or referenced convincing evidence of clinical utility of biomarker testing, whereas more than half made recommendations based on biomarker test results. It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.

  5. Crustal strain accumulation on Southern Basin and Range Province faults modulated by distant plate boundary earthquakes? Evidence from geodesy, seismic imaging, and paleoseismology

    NASA Astrophysics Data System (ADS)

    Bennett, R. A.; Shirzaei, M.; Broermann, J.; Spinler, J. C.; Holland, A. A.; Pearthree, P.

    2014-12-01

    GPS in Arizona reveals a change in the pattern of crustal strain accumulation in 2010 and based on viscoelastic modeling appears to be associated with the distant M7.2 El Mayor-Cucapah (EMC) earthquake in Baja California, Mexico. GPS data collected between 1999 and 2009 near the Santa Rita normal fault in SE Arizona reveal a narrow zone of crustal deformation coincident with the fault trace, delineated by W-NW facing Pleistocene fault scarps of heights 1 to 7 m. The apparent deformation zone is also seen in a preliminary InSAR interferogram. Total motion across the zone inferred using an elastic block model constrained by the pre-2010 GPS measurements is ~1 mm/yr in a sense consistent with normal fault motion. However, continuous GPS measurements throughout Arizona reveal pronounced changes in crustal velocity following the EMC earthquake, such that the relative motion across the Santa Rita fault post-2010 is negligible. Paleoseismic evidence indicates that mapped Santa Rita fault scarps were formed by two or more large magnitude (M6.7 to M7.6) surface rupturing normal-faulting earthquakes 60 to 100 kyrs ago. Seismic refraction and reflection data constrained by deep (~800 m) well log data provide evidence of progressive, possibly intermittent, displacement on the fault through time. The rate of strain accumulation observed geodetically prior to 2010, if constant over the past 60 to 100 kyrs, would imply an untenable minimum slip rate deficit of 60 to 100 m since the most recent earthquake. One explanation for the available geodetic, seismic, and paleoseismic evidence is that strain accumulation is modulated by viscoelastic relaxation associated with frequent large magnitude earthquakes in the Salton Trough region, episodically inhibiting the accumulation of elastic strain required to generate large earthquakes on the Santa Rita and possibly other faults in the Southern Basin and Range. An important question is thus for how long the postseismic velocity changes

  6. Evidence that the Great Pacific Garbage Patch is rapidly accumulating plastic.

    PubMed

    Lebreton, L; Slat, B; Ferrari, F; Sainte-Rose, B; Aitken, J; Marthouse, R; Hajbane, S; Cunsolo, S; Schwarz, A; Levivier, A; Noble, K; Debeljak, P; Maral, H; Schoeneich-Argent, R; Brambini, R; Reisser, J

    2018-03-22

    Ocean plastic can persist in sea surface waters, eventually accumulating in remote areas of the world's oceans. Here we characterise and quantify a major ocean plastic accumulation zone formed in subtropical waters between California and Hawaii: The Great Pacific Garbage Patch (GPGP). Our model, calibrated with data from multi-vessel and aircraft surveys, predicted at least 79 (45-129) thousand tonnes of ocean plastic are floating inside an area of 1.6 million km 2 ; a figure four to sixteen times higher than previously reported. We explain this difference through the use of more robust methods to quantify larger debris. Over three-quarters of the GPGP mass was carried by debris larger than 5 cm and at least 46% was comprised of fishing nets. Microplastics accounted for 8% of the total mass but 94% of the estimated 1.8 (1.1-3.6) trillion pieces floating in the area. Plastic collected during our study has specific characteristics such as small surface-to-volume ratio, indicating that only certain types of debris have the capacity to persist and accumulate at the surface of the GPGP. Finally, our results suggest that ocean plastic pollution within the GPGP is increasing exponentially and at a faster rate than in surrounding waters.

  7. Vascular leakage in dengue--clinical spectrum and influence of parenteral fluid therapy.

    PubMed

    Rosenberger, Kerstin D; Lum, Lucy; Alexander, Neal; Junghanss, Thomas; Wills, Bridget; Jaenisch, Thomas

    2016-03-01

    Clinical management of dengue relies on careful monitoring of fluid balance combined with judicious intravenous (IV) fluid therapy. However, in patients with significant vascular leakage, IV fluids may aggravate serosal fluid accumulation and result in respiratory distress. Trained physicians followed suspected dengue cases prospectively at seven hospitals across Asia and Latin America, using a comprehensive case report form that included daily clinical assessment and detailed documentation of parenteral fluid therapy. Applying Cox regression, we evaluated risk factors for the development of shock or respiratory distress with fluid accumulation. Most confirmed dengue patients (1524/1734, 88%) never experienced dengue shock syndrome (DSS). Among those with DSS, 176/210 (84%) had fluid accumulation, and in the majority (83%), this was detectable clinically. Among all cases with clinically detectable fluid accumulation, 179/447 (40%) were diagnosed with shock or respiratory distress. The risk for respiratory distress with fluid accumulation increased significantly as the infused volume over the preceding 24 h increased (hazard ratio 1.18 per 10 ml/kg increase; P < 0.001). Longer duration of IV therapy, use of a fluid bolus in the preceding 24 h, female gender and poor nutrition also constituted independent risk factors. Shock and respiratory distress are relatively rare manifestations of dengue, but some evidence of fluid accumulation is seen in around 50% of cases. IV fluids play a crucial role in management, but they must be administered with caution. Clinically and/or radiologically detectable fluid accumulations have potential as intermediate severity endpoints for therapeutic intervention trials and/or pathogenesis studies. © 2016 John Wiley & Sons Ltd.

  8. Evidence-based clinical policy: case report of a reproducible process to encourage understanding and evaluation of evidence.

    PubMed

    Rikard-Bell, G; Waters, E; Ward, J

    2006-07-01

    We report within a case study a reproducible process to facilitate the explicit incorporation of evidence by a multidisciplinary group into clinical policy development. To support the decision-making of a multidisciplinary Intersectoral Advisory Group (IAG) convened by the Royal Australasian College of Physicians Health Policy Unit, a systematic review of randomized controlled trials about environmental tobacco smoke and smoking cessation interventions in paediatric settings was first undertaken. As reported in detail here, IAG members were then formally engaged in a transparent and replicable process to understand and interpret the synthesized evidence and to proffer their independent reactions regarding policy, practice and research. Our intention was to ensure that all IAG members were democratically engaged and made aware of the available evidence. As clinical policy must engage stakeholder representatives from diverse backgrounds, a process to equalize understanding of the evidence and 'democratize' judgment about its implications is needed. Future research must then examine the benefits of such explicit steps when guidelines, in turn, are implemented. We hypothesize that changes to future practice will be more likely if processes undertaken to develop guidelines are transparent to clinicians and other target groups.

  9. Neural chronometry and coherency across speed-accuracy demands reveal lack of homomorphism between computational and neural mechanisms of evidence accumulation.

    PubMed

    Heitz, Richard P; Schall, Jeffrey D

    2013-10-19

    The stochastic accumulation framework provides a mechanistic, quantitative account of perceptual decision-making and how task performance changes with experimental manipulations. Importantly, it provides an elegant account of the speed-accuracy trade-off (SAT), which has long been the litmus test for decision models, and also mimics the activity of single neurons in several key respects. Recently, we developed a paradigm whereby macaque monkeys trade speed for accuracy on cue during visual search task. Single-unit activity in frontal eye field (FEF) was not homomorphic with the architecture of models, demonstrating that stochastic accumulators are an incomplete description of neural activity under SAT. This paper summarizes and extends this work, further demonstrating that the SAT leads to extensive, widespread changes in brain activity never before predicted. We will begin by reviewing our recently published work that establishes how spiking activity in FEF accomplishes SAT. Next, we provide two important extensions of this work. First, we report a new chronometric analysis suggesting that increases in perceptual gain with speed stress are evident in FEF synaptic input, implicating afferent sensory-processing sources. Second, we report a new analysis demonstrating selective influence of SAT on frequency coupling between FEF neurons and local field potentials. None of these observations correspond to the mechanics of current accumulator models.

  10. Evidence-based integrative medicine in clinical veterinary oncology.

    PubMed

    Raditic, Donna M; Bartges, Joseph W

    2014-09-01

    Integrative medicine is the combined use of complementary and alternative medicine with conventional or traditional Western medicine systems. The demand for integrative veterinary medicine is growing, but evidence-based research on its efficacy is limited. In veterinary clinical oncology, such research could be translated to human medicine, because veterinary patients with spontaneous tumors are valuable translational models for human cancers. An overview of specific herbs, botanics, dietary supplements, and acupuncture evaluated in dogs, in vitro canine cells, and other relevant species both in vivo and in vitro is presented for their potential use as integrative therapies in veterinary clinical oncology. Published by Elsevier Inc.

  11. Relationships between evidence-based practice, quality improvement and clinical error experience of nurses in Korean hospitals.

    PubMed

    Hwang, Jee-In; Park, Hyeoun-Ae

    2015-07-01

    This study investigated individual and work-related factors associated with nurses' perceptions of evidence-based practice (EBP) and quality improvement (QI), and the relationships between evidence-based practice, quality improvement and clinical errors. Understanding the factors affecting evidence-based practice and quality improvement activities and their relationships with clinical errors is important for designing strategies to promote evidence-based practice, quality improvement and patient safety. A cross-sectional survey was conducted with 594 nurses in two Korean teaching hospitals using the evidence-based practice Questionnaire and quality improvement scale developed in this study. Four hundred and forty-three nurses (74.6%) returned the completed survey. Nurses' ages and educational levels were significantly associated with evidence-based practice scores whereas age and job position were associated with quality improvement scores. There were positive, moderate correlations between evidence-based practice and quality improvement scores. Nurses who had not made any clinical errors during the past 12 months had significantly higher quality improvement skills scores than those who had. The findings indicated the necessity of educational support regarding evidence-based practice and quality improvement for younger staff nurses who have no master degrees. Enhancing quality improvement skills may reduce clinical errors. Nurse managers should consider the characteristics of their staff when implementing educational and clinical strategies for evidence-based practice and quality improvement. © 2013 John Wiley & Sons Ltd.

  12. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy.

    PubMed

    Kreiner, D Scott; Hwang, Steven W; Easa, John E; Resnick, Daniel K; Baisden, Jamie L; Bess, Shay; Cho, Charles H; DePalma, Michael J; Dougherty, Paul; Fernand, Robert; Ghiselli, Gary; Hanna, Amgad S; Lamer, Tim; Lisi, Anthony J; Mazanec, Daniel J; Meagher, Richard J; Nucci, Robert C; Patel, Rakesh D; Sembrano, Jonathan N; Sharma, Anil K; Summers, Jeffrey T; Taleghani, Christopher K; Tontz, William L; Toton, John F

    2014-01-01

    The objective of the North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of lumbar disc herniation with radiculopathy. The guideline is intended to reflect contemporary treatment concepts for symptomatic lumbar disc herniation with radiculopathy as reflected in the highest quality clinical literature available on this subject as of July 2011. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder. To provide an evidence-based educational tool to assist spine specialists in the diagnosis and treatment of lumbar disc herniation with radiculopathy. Systematic review and evidence-based clinical guideline. This guideline is a product of the Lumbar Disc Herniation with Radiculopathy Work Group of NASS' Evidence-Based Guideline Development Committee. The work group consisted of multidisciplinary spine care specialists trained in the principles of evidence-based analysis. A literature search addressing each question and using a specific search protocol was performed on English-language references found in Medline, Embase (Drugs and Pharmacology), and four additional evidence-based databases to identify articles. The relevant literature was then independently rated using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final recommendations to answer each clinical question were developed via work group discussion, and grades were assigned to the recommendations using standardized grades of recommendation. In the absence of Level I to IV evidence, work group consensus statements have been developed using a modified nominal group technique, and these statements are clearly identified as such in the guideline

  13. Biomechanics of the thorax - research evidence and clinical expertise.

    PubMed

    Lee, Diane Gail

    2015-07-01

    Understanding the biomechanics of the thorax is critical for understanding its role in multiple conditions since the thorax is part of many integrated systems including the musculoskeletal, respiratory, cardiac, digestive and urogynecological. The thorax is also an integrated system within itself and an element of the whole body/person. Therefore, understanding the biomechanics of the thorax is fundamental to all forms of treatment for multiple conditions. The interpretation of movement examination findings depends on one's view of optimal biomechanics and the influential factors. This article will provide a synopsis of the current state of research evidence as well as observations from clinical experience pertaining to the biomechanics of the thorax in order to help clinicians organise this knowledge and facilitate evidence-based and informed management of the, often complex, patient with or without thoracic pain and impairment. The integrated systems model (ISM) will be introduced as a way to determine when the noted biomechanical findings are relevant to a patient's clinical presentation.

  14. The Zero Suicide Model: Applying Evidence-Based Suicide Prevention Practices to Clinical Care

    PubMed Central

    Brodsky, Beth S.; Spruch-Feiner, Aliza; Stanley, Barbara

    2018-01-01

    Suicide is reaching epidemic proportions, with over 44,000 deaths by suicide in the US, and 800,000 worldwide in 2015. This, despite research and development of evidence-based interventions that target suicidal behavior directly. Suicide prevention efforts need a comprehensive approach, and research must lead to effective implementation across public and mental health systems. A 10-year systematic review of evidence-based findings in suicide prevention summarized the areas necessary for translating research into practice. These include risk assessment, means restriction, evidence-based treatments, population screening combined with chain of care, monitoring, and follow-up. In this article, we review how suicide prevention research informs implementation in clinical settings where those most at risk present for care. Evidence-based and best practices address the fluctuating nature of suicide risk, which requires ongoing risk assessment, direct intervention and monitoring. In the US, the National Action Alliance for Suicide Prevention has put forth the Zero Suicide (ZS) Model, a framework to coordinate a multilevel approach to implementing evidence-based practices. We present the Assess, Intervene and Monitor for Suicide Prevention model (AIM-SP) as a guide for implementation of ZS evidence-based and best practices in clinical settings. Ten basic steps for clinical management model will be described and illustrated through case vignette. These steps are designed to be easily incorporated into standard clinical practice to enhance suicide risk assessment, brief interventions to increase safety and teach coping strategies and to improve ongoing contact and monitoring of high-risk individuals during transitions in care and high risk periods. PMID:29527178

  15. Access to orphan drugs despite poor quality of clinical evidence

    PubMed Central

    Dupont, Alain G; Van Wilder, Philippe B

    2011-01-01

    AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641

  16. Plasmapheresis in immune hematology: review of clinical outcome data with respect to evidence-based medicine and clinical experience.

    PubMed

    von Baeyer, Hans

    2003-02-01

    The objective of this paper is to assess the role of plasmapheresis in immune hematology by reviewing published clinical outcome data and narrative review articles. This information will be used to define evidence levels for appraisal of the efficacy and rank of plasmapheresis among other management options. This evidence-based strategy conforms to the concepts of the American Society of Hematology (ASH). as put forward in 1996 in the context of immune thrombocytopenia (ITP) treatment. The term 'experimental' is used to describe indications where the only scientific evidence of the efficacy of plasmapheresis consists of pathophysiological reasoning and empiric clinical findings. We reviewed the available literature on the use of plasmapheresis in autoimmune hemolytic anemia (AIHA), hemolytic disease of the newborn (HDN), autoimmune thrombocytopenic purpura (AITP), heparin-induced thrombocytopenia type II (HIT II), post-transfusion purpura (PTP), refractoriness to platelet transfusion (RPT), coagulation factor inhibitor (CFI) and catastrophic antiphospholipid syndrome (CAS). Plasmapheresis completes the spectrum of management options as it eliminates physically circulating free antibodies involved in the pathogenesis of these immune hematological syndromes. Because of the paucity of data, evidence levels had to be defined based on the findings of uncontrolled case series and the opinions of independent experts. In many cases, randomized clinical trials were not feasible because the syndromes are so rare. When defined as an 'experimental indication', plasmapheresis has a firm scientific basis, but larger scale clinical experience with the method is still lacking. In these cases, the detection and monitoring of symptomatic disease-related circulating free antibodies or immune complexes is a mandatory prerequisite for the use of plasmapheresis. The therapeutic benefit of plasmapheresis is substantiated by the level V of evidence of its efficacy in treatment of HDN, HIV

  17. 'Personalised evidence' for personalised healthcare: integration of a clinical librarian into mental health services - a feasibility study.

    PubMed

    Steele, Rachel; Tiffin, Paul A

    2014-02-01

    Aims and method To evaluate the feasibility of integrating a clinical librarian (CL) within four mental health teams. A CL was attached to three clinical teams and the Trustwide Psychology Research and Clinical Governance Structure for 12 months. Requests for evidence syntheses were recorded. The perceived impact of individual evidence summaries on staff activities was evaluated using a brief online questionnaire. Results Overall, 82 requests for evidence summaries were received: 50% related to evidence for individual patient care, 23% to generic clinical issues and 27% were on management/corporate topics. In the questionnaires 105 participants indicated that the most common impact on their practice was advice given to colleagues (51 respondents), closely followed by the evidence summaries stimulating new ideas for patient care or treatment (50 respondents). Clinical implications The integration of a CL into clinical and corporate teams is feasible and perceived as having an impact on staff activities. A CL may be able to collate 'personalised evidence' which may enhance individualised healthcare. In some cases the usual concept of a hierarchy of evidence may not easily apply, with case reports providing guidance which may be more applicable than population-based studies.

  18. Evidence-based practice exposure and physiotherapy students' behaviour during clinical placements: a survey.

    PubMed

    Olsen, Nina Rydland; Lygren, Hildegunn; Espehaug, Birgitte; Nortvedt, Monica Wammen; Bradley, Peter; Bjordal, Jan Magnus

    2014-12-01

    Physiotherapists are expected to practice in an evidence-based way. Evidence-based practice (EBP) should be an integral part of the curriculum to ensure use of the five EBP steps: asking clinical questions, searching for and appraising research evidence, integrating the evidence into clinical practice and evaluating this process. The aim of this study was to compare self-reported EBP behaviour, abilities and barriers during clinical placements reported by five cohorts of final year physiotherapy students' with different EBP exposure across the 3-year bachelor programme. A cross-sectional study was conducted among five cohorts (2006-2010) with third year physiotherapy students at a University College in Norway. In total, 246 students were eligible for this study. To collect data, we used a questionnaire with 42 items related to EBP behaviour, ability and barriers. Associations were investigated using the Spearman's rho (r). In total, 180 out of 246 third year physiotherapy students, who had recently completed a clinical placement, filled out the questionnaire (73 %). The association between the level of EBP exposure and students' self-reported EBP behaviour, abilities and barriers was low for most items in the questionnaire. Statistically significant correlations were found for eight items, related to information need, question formulation, use of checklists, searching and perceived ability to search for and critically appraise research evidence. The strongest correlation was found between the level of EBP exposure and ability to critically appraise research evidence (r = 0.41, p < 0.001). An association between the level of EBP exposure and physiotherapy students' EBP behaviour was found for elements such as asking and searching, ability to search for and critically appraise research evidence, and experience of critical appraisal as a barrier. Further research need to explore strategies for EBP exposure throughout the curriculum, regarding content, timing

  19. Expediting the transfer of evidence into practice: building clinical partnerships*

    PubMed Central

    Rader, Tamara; Gagnon, Anita J.

    2000-01-01

    A librarian/clinician partnership was fostered in one hospital through the formation of the Evidence-based Practice Committee, with an ulterior goal of facilitating the transfer of evidence into practice. The paper will describe barriers to evidence-based practice and outline the committee's strategies for overcoming these barriers, including the development and promotion of a Web-based guide to evidence-based practice specifically designed for clinicians (health professionals). Educational strategies for use of the Web-based guide will also be addressed. Advantages of this partnership are that the skills of librarians in meeting the needs of clinicians are maximized. The evidence-based practice skills of clinicians are honed and librarians make a valuable contribution to the knowledgebase of the clinical staff. The knowledge acquired through the partnership by both clinicians and librarians will increase the sophistication of the dialogue between the two groups and in turn will expedite the transfer of evidence into practice. PMID:10928710

  20. Evidence-Based Diagnosis: Incorporating Diagnostic Instruments into Clinical Practice

    ERIC Educational Resources Information Center

    Doss, Amanda Jensen

    2005-01-01

    This article is intended to serve as a practical guide for practitioners interested in incorporating evidence-based diagnosis (EBD) instruments into their clinical practices to refine the diagnostic process. Three measures are used to illustrate this process, the DISC-IV (Shaffer et al., 2000), the Schedule for Affective Disorders and…

  1. Exercise and physical activity in mental disorders: clinical and experimental evidence.

    PubMed

    Zschucke, Elisabeth; Gaudlitz, Katharina; Ströhle, Andreas

    2013-01-01

    Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

  2. Promoting physical therapists' of research evidence to inform clinical practice: part 1--theoretical foundation, evidence, and description of the PEAK program.

    PubMed

    Tilson, Julie K; Mickan, Sharon

    2014-06-25

    There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists' integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura's social cognitive theory and Malcolm Knowles's adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a "Best Practices List" - a list of locally generated, evidence-based, actionable behaviors relevant to the groups' clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program - an educational program designed to

  3. Promoting physical therapists’ of research evidence to inform clinical practice: part 1 - theoretical foundation, evidence, and description of the PEAK program

    PubMed Central

    2014-01-01

    Background There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists’ integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura’s social cognitive theory and Malcolm Knowles’s adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. Discussion The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a “Best Practices List” - a list of locally generated, evidence-based, actionable behaviors relevant to the groups’ clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. Summary This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program

  4. The experience of Australian project leaders in encouraging practitioners to adopt research evidence in their clinical practice.

    PubMed

    Henderson, Amanda J; Davies, Jan; Willet, Michaela R

    2006-11-01

    This paper describes a qualitative program evaluation which sought to identify factors that either assist or impede the adoption of clinical evidence in everyday practice. Thirteen Australian projects were funded in a competitive grant program to adopt innovative strategies to improve the uptake of research evidence in everyday clinical practice. Project leaders' reports were analysed to collate common themes related to 1) critical elements in successful application of research knowledge, 2) barriers to implementing evidence, and 3) lessons for other organisations that might implement a similar project. Despite the diversity of the methods used to establish projects and the range of topics and clinical settings, many similarities were identified in the perceived critical success elements, barriers, and lessons for adopting clinical evidence. Eighteen themes emerged across the data including: leadership support; key stakeholder involvement; practice changes; communication; resources; education of staff; evaluation of outcomes; consumers; knowledge gaps; adoption/implementing staff; access to knowledge; risk assessment; collaboration; effectiveness of clinical research evidence; structure/organisation; cultural barriers; previous experiences; and information technology. Leaders of projects to adopt evidence in clinical practice identified barriers, critical success elements and lessons that impacted on their projects. A range of influences on the adoption of evidence were identified, and this knowledge can be used to assist others undertaking similar projects.

  5. Modulation of obesity-induced inflammation by dietary fats: mechanisms and clinical evidence

    PubMed Central

    2014-01-01

    Obesity plays a pivotal role in the development of low-grade inflammation. Dietary fatty acids are important modulators of inflammatory responses. Saturated fatty acids (SFA) and n-6 polyunsaturated fatty acids (PUFA) have been reported to exert pro-inflammatory effects. n-3 PUFA in particular, possess anti-inflammatory properties. Numerous clinical studies have been conducted over decades to investigate the impact of dietary fatty acids on inflammatory response in obese individuals, however the findings remained uncertain. High fat meals have been reported to increase pro-inflammatory responses, however there is limited evidence to support the role of individual dietary fatty acids in a postprandial state. Evidence in chronic studies is contradictory, the effects of individual dietary fatty acids deserves further attention. Weight loss rather than n-3 PUFA supplementation may play a more prominent role in alleviating low grade inflammation. In this context, the present review provides an update on the mechanistic insight and the influence of dietary fats on low grade inflammation, based on clinical evidence from acute and chronic clinical studies in obese and overweight individuals. PMID:24476102

  6. Reasoning, evidence, and clinical decision-making: The great debate moves forward.

    PubMed

    Loughlin, Michael; Bluhm, Robyn; Buetow, Stephen; Borgerson, Kirstin; Fuller, Jonathan

    2017-10-01

    When the editorial to the first philosophy thematic edition of this journal was published in 2010, critical questioning of underlying assumptions, regarding such crucial issues as clinical decision making, practical reasoning, and the nature of evidence in health care, was still derided by some prominent contributors to the literature on medical practice. Things have changed dramatically. Far from being derided or dismissed as a distraction from practical concerns, the discussion of such fundamental questions, and their implications for matters of practical import, is currently the preoccupation of some of the most influential and insightful contributors to the on-going evidence-based medicine debate. Discussions focus on practical wisdom, evidence, and value and the relationship between rationality and context. In the debate about clinical practice, we are going to have to be more explicit and rigorous in future in developing and defending our views about what is valuable in human life. © 2017 John Wiley & Sons, Ltd.

  7. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  8. Spirulina in Clinical Practice: Evidence-Based Human Applications

    PubMed Central

    Karkos, P. D.; Leong, S. C.; Karkos, C. D.; Sivaji, N.; Assimakopoulos, D. A.

    2011-01-01

    Spirulina or Arthrospira is a blue-green alga that became famous after it was successfully used by NASA as a dietary supplement for astronauts on space missions. It has the ability to modulate immune functions and exhibits anti-inflammatory properties by inhibiting the release of histamine by mast cells. Multiple studies investigating the efficacy and the potential clinical applications of Spirulina in treating several diseases have been performed and a few randomized controlled trials and systematic reviews suggest that this alga may improve several symptoms and may even have an anticancer, antiviral and antiallergic effects. Current and potential clinical applications, issues of safety, indications, side-effects and levels of evidence are addressed in this review. Areas of ongoing and future research are also discussed. PMID:18955364

  9. A systematic review of evidence relating to clinical supervision for nurses, midwives and allied health professionals.

    PubMed

    Pollock, Alex; Campbell, Pauline; Deery, Ruth; Fleming, Mick; Rankin, Jean; Sloan, Graham; Cheyne, Helen

    2017-08-01

    The aim of this study was to systematically review evidence relating to clinical supervision for nurses, midwives and allied health professionals. Since 1902 statutory supervision has been a requirement for UK midwives, but this is due to change. Evidence relating to clinical supervision for nurses and allied health professions could inform a new model of clinical supervision for midwives. A systematic review with a contingent design, comprising a broad map of research relating to clinical supervision and two focussed syntheses answering specific review questions. Electronic databases were searched from 2005 - September 2015, limited to English-language peer-reviewed publications. Systematic reviews evaluating the effectiveness of clinical supervision were included in Synthesis 1. Primary research studies including a description of a clinical supervision intervention were included in Synthesis 2. Quality of reviews were judged using a risk of bias tool and review results summarized in tables. Data describing the key components of clinical supervision interventions were extracted from studies included in Synthesis 2, categorized using a reporting framework and a narrative account provided. Ten reviews were included in Synthesis 1; these demonstrated an absence of convincing empirical evidence and lack of agreement over the nature of clinical supervision. Nineteen primary studies were included in Synthesis 2; these highlighted a lack of consistency and large variations between delivered interventions. Despite insufficient evidence to directly inform the selection and implementation of a framework, the limited available evidence can inform the design of a new model of clinical supervision for UK-based midwives. © 2017 John Wiley & Sons Ltd.

  10. Balancing health care evidence and art to meet clinical needs: policymakers' perspectives.

    PubMed

    Parker, Louise E; Ritchie, Mona J; Kirchner, Joann E; Owen, Richard R

    2009-12-01

    Rationale, aims and objectives Although many believe that evidence-based practice (EBP) has great potential, critics have identified limitations including a focus on randomized clinical trial (RCT) evidence to the exclusion of other evidence types and a disregard for the art of medicine. Others have argued, however, that proper application of EBP involves reasoned consideration of a wide variety of information; thus, the dichotomy between medical science and art may be false. We explore the views of executive-level policymakers from the Veterans Health Administration, a leader in the EBP movement, regarding what constitutes evidence and the relative importance of evidence versus practical needs when determining clinical policy. Method We conducted 26 semi-structured qualitative interviews and performed a content analysis. Results Although informants generally believed in the value of EBP and the role of RCTs within it, they also valued other types of evidence. Further, they had concerns that were sometimes antithetical with strict adherence to an evidence-based approach. These included practical concerns, fit with organizational values and with local circumstances, resources, political pressures and patient needs. They were especially concerned about how to address medical conditions that affect many individuals or high-risk populations that have no evidence-based treatment. Conclusion When possible, health care practice should be evidence-based. When this is not possible, health care providers must turn to the art of medicine by using consensus-based best practices. Further, it is important for policymakers and researchers to work in concert to develop EBPs that are practical and meet needs.

  11. The role of hypnotherapy in evidence-based clinical practice.

    PubMed

    Griffiths, M J

    2017-05-01

    The purpose of this review was to discuss the place of hypnotherapy in a modern medical world dominated by so-called evidence-based clinical practice. Hypnosis is an easily learned technique that is a valuable adjuvant to many medical, dental and psychological interventions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Guideline summary review: an evidence-based clinical guideline for the diagnosis and treatment of adult isthmic spondylolisthesis.

    PubMed

    Kreiner, D Scott; Baisden, Jamie; Mazanec, Daniel J; Patel, Rakesh D; Bess, Robert S; Burton, Douglas; Chutkan, Norman B; Cohen, Bernard A; Crawford, Charles H; Ghiselli, Gary; Hanna, Amgad S; Hwang, Steven W; Kilincer, Cumhur; Myers, Mark E; Park, Paul; Rosolowski, Karie A; Sharma, Anil K; Taleghani, Christopher K; Trammell, Terry R; Vo, Andrew N; Williams, Keith D

    2016-12-01

    The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Adult Isthmic Spondylolisthesis features evidence-based recommendations for diagnosing and treating adult patients with isthmic spondylolisthesis. The guideline is intended to reflect contemporary treatment concepts for symptomatic isthmic spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of June 2013. NASS' guideline on this topic is the only guideline on adult isthmic spondylolisthesis accepted in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse. The purpose of the guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for adult patients with isthmic spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. This is a guideline summary review. This guideline is the product of the Adult Isthmic Spondylolisthesis Work Group of NASS' Evidence-Based Clinical Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questionsto address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members utilized NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when

  13. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  14. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

    PubMed

    Dweik, Raed A; Boggs, Peter B; Erzurum, Serpil C; Irvin, Charles G; Leigh, Margaret W; Lundberg, Jon O; Olin, Anna-Carin; Plummer, Alan L; Taylor, D Robin

    2011-09-01

    Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice. To develop evidence-based guidelines for the interpretation of Fe(NO) measurements that incorporate evidence that has accumulated over the past decade. We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. The evidence related to the use of Fe(NO) measurements is reviewed and clinical practice recommendations are provided. In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV(1) reversibility or provocation tests are only indirectly associated with airway inflammation. Fe(NO) offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy.

  15. Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

    PubMed

    Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-02-01

    Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

  16. Barriers to implementing evidence-based clinical guidelines: A survey of early adopters

    PubMed Central

    Spallek, Heiko; Song, Mei; Polk, Deborah E; Bekhuis, Tanja; Frantsve-Hawley, Julie; Aravamudhan, Krishna

    2010-01-01

    Objective The purpose of this study is to identify barriers that early-adopting dentists perceive as common and challenging when implementing recommendations from evidence-based (EB) clinical guidelines. Method This is a cross-sectional study. Dentists who attended the 2008 Evidence-based Dentistry Champion Conference were eligible for inclusion. Forty-three dentists (34%) responded to a 22-item questionnaire administered online. Two investigators independently coded and categorized responses to open-ended items. Descriptive statistics were computed to assess the frequency of barriers and perceived challenges. Results The most common barriers to implementation are difficulty in changing current practice model, resistance and criticism from colleagues, and lack of trust in evidence or research. Barriers perceived as serious problems have to do with lack of up-to-date evidence, lack of clear answers to clinical questions, and contradictory information in the scientific literature. Conclusions Knowledge of barriers will help improve translation of biomedical research for dentists. Information in guidelines needs to be current, clear, and simplified for use at chairside; dentists’ fears need to be addressed. PMID:21093800

  17. Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials.

    PubMed

    Mitchell, P; Korobelnik, J-F; Lanzetta, P; Holz, F G; Prünte, C; Schmidt-Erfurth, U; Tano, Y; Wolf, S

    2010-01-01

    Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

  18. Clinical and Imaging Presentation of a Patient with Beta-Propeller Protein-Associated Neurodegeneration, a Rare and Sporadic form of Neurodegeneration with Brain Iron Accumulation (NBIA).

    PubMed

    Hattingen, Elke; Handke, Nikolaus; Cremer, Kirsten; Hoffjan, Sabine; Kukuk, Guido Matthias

    2017-12-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of inherited neurologic disorders with iron accumulation in the basal ganglia, which share magnetic resonance (MR) imaging characteristics, histopathologic and clinical features. According to the affected basal nuclei, clinical features include extrapyramidal movement disorders and varying degrees of intellectual disability status. The most common NBIA subtype is caused by pathogenic variants in PANK2. The hallmark of MR imaging in patients with PANK2 mutations is an eye-of-the-tiger sign in the globus pallidus. We report a 33-year-old female with a rare subtype of NBIA, called beta-propeller protein-associated neurodegeneration (BPAN) with a hitherto unknown missense variant in WDR45. She presented with BPAN's particular biphasic course of neurological symptoms and with a dominant iron accumulation in the midbrain that enclosed a spotty T2-hyperintensity.

  19. Accumulation of 5-Oxoproline in Mouse Tissues After Inhibition of 5-Oxoprolinase and Administration of Amino Acids: Evidence for Function of the γ-Glutamyl Cycle*

    PubMed Central

    Van Der Werf, Paul; Stephani, Ralph A.; Meister, Alton

    1974-01-01

    5-Oxoprolinase catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate, L-2-pyrrolidone-5-carboxylate) to L-glutamate with concomitant stoichiometric cleavage of ATP to ADP and inorganic orthophosphate. In this reaction, a step in the γ-glutamyl cycle, 5-oxoproline (formed by the action of γ-glutamylcyclotransferase on γ-glutamyl amino acids, which are in turn formed by transpeptidation of amino acids with glutathione), is made available for glutathione synthesis. When mice are injected with L-2-imidazolidone-4-carboxylate, a competitive inhibitor of 5-oxoprolinase, they accumulate 5-oxoproline in their tissues (kidney, liver, brain, and eye) and excrete it in the urine. Mice given the inhibitor together with one of several L-amino acids accumulate and excrete much more 5-oxoproline than when they are given the inhibitor alone. Such augmentation of 5-oxoproline accumulation offers evidence for the function of the γ-glutamyl cycle in vivo and supports the view that 5-oxoproline is a quantitatively significant metabolite. Images PMID:4151516

  20. Advancing the Scientific Foundation for Evidence-Based Practice in Clinical Child and Adolescent Psychology.

    PubMed

    Roberts, Michael C; Blossom, Jennifer B; Evans, Spencer C; Amaro, Christina M; Kanine, Rebecca M

    2017-01-01

    Evidence-based practice (EBP) has become a central focus in clinical child and adolescent psychology. As originally defined, EBP in psychology is the integration of the best available research evidence, patient characteristics, and clinical expertise. Although evidence-based perspectives have garnered widespread acceptance in recent years, there has also been some confusion and disagreement about the 3-part definition of EBP, particularly the role of research. In this article, we first provide a brief review of the development of EBP in clinical child and adolescent psychology. Next, we outline the following 4 points to help clarify the understanding of EBP: (a) knowledge should not be confused with epistemic processes, (b) research on clinician and client factors is needed for EBP, (c) research on assessment is needed for EBP, and (d) the 3-part conceptualization of EBP can serve as a useful framework to guide research. Based on these principles, we put forth a slightly revised conceptualization of EBP, in which the role of research is expanded and more clearly operationalized. Finally, based on our review of the literature, we offer illustrative examples of specific directions for future research to advance the evidence base for EBP in clinical child and adolescent psychology.

  1. Biomechanics of the thorax – research evidence and clinical expertise

    PubMed Central

    Lee, Diane Gail

    2015-01-01

    Understanding the biomechanics of the thorax is critical for understanding its role in multiple conditions since the thorax is part of many integrated systems including the musculoskeletal, respiratory, cardiac, digestive and urogynecological. The thorax is also an integrated system within itself and an element of the whole body/person. Therefore, understanding the biomechanics of the thorax is fundamental to all forms of treatment for multiple conditions. The interpretation of movement examination findings depends on one's view of optimal biomechanics and the influential factors. This article will provide a synopsis of the current state of research evidence as well as observations from clinical experience pertaining to the biomechanics of the thorax in order to help clinicians organise this knowledge and facilitate evidence-based and informed management of the, often complex, patient with or without thoracic pain and impairment. The integrated systems model (ISM) will be introduced as a way to determine when the noted biomechanical findings are relevant to a patient's clinical presentation. PMID:26309383

  2. Consensus Recommendations for Systematic Evaluation of Drug-Drug Interaction Evidence for Clinical Decision Support

    PubMed Central

    Scheife, Richard T.; Hines, Lisa E.; Boyce, Richard D.; Chung, Sophie P.; Momper, Jeremiah; Sommer, Christine D.; Abernethy, Darrell R.; Horn, John; Sklar, Stephen J.; Wong, Samantha K.; Jones, Gretchen; Brown, Mary; Grizzle, Amy J.; Comes, Susan; Wilkins, Tricia Lee; Borst, Clarissa; Wittie, Michael A.; Rich, Alissa; Malone, Daniel C.

    2015-01-01

    Background Healthcare organizations, compendia, and drug knowledgebase vendors use varying methods to evaluate and synthesize evidence on drug-drug interactions (DDIs). This situation has a negative effect on electronic prescribing and medication information systems that warn clinicians of potentially harmful medication combinations. Objective To provide recommendations for systematic evaluation of evidence from the scientific literature, drug product labeling, and regulatory documents with respect to DDIs for clinical decision support. Methods A conference series was conducted to develop a structured process to improve the quality of DDI alerting systems. Three expert workgroups were assembled to address the goals of the conference. The Evidence Workgroup consisted of 15 individuals with expertise in pharmacology, drug information, biomedical informatics, and clinical decision support. Workgroup members met via webinar from January 2013 to February 2014. Two in-person meetings were conducted in May and September 2013 to reach consensus on recommendations. Results We developed expert-consensus answers to three key questions: 1) What is the best approach to evaluate DDI evidence?; 2) What evidence is required for a DDI to be applicable to an entire class of drugs?; and 3) How should a structured evaluation process be vetted and validated? Conclusion Evidence-based decision support for DDIs requires consistent application of transparent and systematic methods to evaluate the evidence. Drug information systems that implement these recommendations should be able to provide higher quality information about DDIs in drug compendia and clinical decision support tools. PMID:25556085

  3. Exercise Exerts Its Beneficial Effects on Acute Coronary Syndrome: Clinical Evidence.

    PubMed

    Liu, Zhuyuan; Gu, Huanyu; Dai, Qiying; Wang, Hongbao; Yao, Jianhua; Zhou, Lei

    2017-01-01

    Acute coronary syndrome (ACS) is characterized with high morbidity, high mortality, long hospitalization and frequent revisits. It has been the most serious coronary artery diseases in the world. A large body of clinical evidence demonstrates that exercise is associated with reduced cardiovascular disease risk. In addition, different types of exercise have become the central to most cardiac rehabilitation/risk reduction programs. However, the detailed effects of exercise in ACS is still unclear and there is still lack of evidence on which exercise regimen may be ideal for ACS. This chapter presents a brief review of the pathophysiology of ACS and the relationship between exercise and the cardiovascular system. Besides that, this chapter also provide an updated discussion of the most relevant discoveries regarding to exercise and its role in managing ACS in clinical studies.

  4. How to write a Critically Appraised Topic: evidence to underpin routine clinical practice.

    PubMed

    Callander, J; Anstey, A V; Ingram, J R; Limpens, J; Flohr, C; Spuls, P I

    2017-10-01

    Critically appraised topics (CATs) are essential tools for busy clinicians who wish to ensure that their daily clinical practice is underpinned by evidence-based medicine. CATs are short summaries of the most up-to-date, high-quality available evidence that is found using thorough structured methods. They can be used to answer specific, patient-orientated questions that arise recurrently in real-life practice. This article provides readers with a detailed guide to performing their own CATs. It is split into four main sections reflecting the four main steps involved in performing a CAT: formulation of a focused question, a search for the most relevant and highest-quality evidence, critical appraisal of the evidence and application of the results back to the patient scenario. As well as helping to improve patient care on an individual basis by answering specific clinical questions that arise, CATs can help spread and share knowledge with colleagues on an international level through publication in the evidence-based dermatology section of the British Journal of Dermatology. © 2017 British Association of Dermatologists.

  5. Addressing unwarranted clinical variation: A rapid review of current evidence.

    PubMed

    Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

    2018-05-15

    Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and

  6. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications

    PubMed Central

    Dweik, Raed A.; Boggs, Peter B.; Erzurum, Serpil C.; Irvin, Charles G.; Leigh, Margaret W.; Lundberg, Jon O.; Olin, Anna-Carin; Plummer, Alan L.; Taylor, D. Robin

    2011-01-01

    Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While FeNO measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of FeNO in clinical practice. Purpose: To develop evidence-based guidelines for the interpretation of FeNO measurements that incorporate evidence that has accumulated over the past decade. Methods: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. Results: The evidence related to the use of FeNO measurements is reviewed and clinical practice recommendations are provided. Conclusions: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV1 reversibility or provocation tests are only indirectly associated with airway inflammation. FeNO offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy. PMID:21885636

  7. Influence of evidence-based guidance on health policy and clinical practice in England.

    PubMed

    Coleman, P; Nicholl, J

    2001-12-01

    To examine the influence of evidence-based guidance on health care decisions, a study of the use of seven different sources and types of evidence-based guidance was carried out in senior health professionals in England with responsibilities either for directing and purchasing health care based in the health authorities, or providing clinical care to patients in trust hospitals or in primary care. Postal survey. Three health settings: 46 health authorities, 162 acute and/or community trust hospitals, and 96 primary care groups in England. 566 subjects (46 directors of public health, 49 directors of purchasing, 375 clinical directors/consultants in hospitals, and 96 lead general practitioners). Knowledge of selected evidence-based guidance, previous use ever, beliefs in quality, usefulness, and perceived influence on practice. A usable response rate of 73% (407/560) was achieved; 82% (334/407) of respondents had consulted at least one source of evidence-based guidance ever in the past. Professionals in the health authorities were much more likely to be aware of the evidence-based guidance and had consulted more sources (mean number of different guidelines consulted 4.3) than either the hospital consultants (mean 1.9) or GPs in primary care (mean 1.8). There was little variation in the belief that the evidence-based guidance was of "good quality", but respondents from the health authorities (87%) were significantly more likely than either hospital consultants (52%) or GPs (57%) to perceive that any of the specified evidence-based guidance had influenced a change of practice. Across all settings, the least used route to accessing evidence-based guidance was the Internet. For several sources an effect was observed between use ever, the health region where the health professional worked, and the region where the guidance was produced or published. This was evident for some national sources as well as in those initiatives produced locally with predominantly local

  8. Guideline summary review: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis.

    PubMed

    Matz, Paul G; Meagher, R J; Lamer, Tim; Tontz, William L; Annaswamy, Thiru M; Cassidy, R Carter; Cho, Charles H; Dougherty, Paul; Easa, John E; Enix, Dennis E; Gunnoe, Bryan A; Jallo, Jack; Julien, Terrence D; Maserati, Matthew B; Nucci, Robert C; O'Toole, John E; Rosolowski, Karie; Sembrano, Jonathan N; Villavicencio, Alan T; Witt, Jens-Peter

    2016-03-01

    The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. The NASS guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. A systematic review of clinical studies relevant to degenerative spondylolisthesis was carried out. This NASS spondyolisthesis guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members used the NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members

  9. [Lorenz was right, or does aggressive energy accumulate?].

    PubMed

    Kudriavtseva, N N

    2004-06-01

    Evidence supporting the fact that inherited mechanisms of regulation of aggressive behavior as a result of a repeated experience of aggression ending in victories are transformed into pathological mechanisms based on accumulation of neurochemical shifts in the brain, enhancing aggressiveness, and forming aggressive motivation in aggressive winners. This confirms the concept by Lorenz on the existence of a mechanism (but not instinct) of a spontaneous accumulation of aggressive energy that needs a discharge and formation of permanent attraction to manifestation of aggression.

  10. Architecture for knowledge-based and federated search of online clinical evidence.

    PubMed

    Coiera, Enrico; Walther, Martin; Nguyen, Ken; Lovell, Nigel H

    2005-10-24

    It is increasingly difficult for clinicians to keep up-to-date with the rapidly growing biomedical literature. Online evidence retrieval methods are now seen as a core tool to support evidence-based health practice. However, standard search engine technology is not designed to manage the many different types of evidence sources that are available or to handle the very different information needs of various clinical groups, who often work in widely different settings. The objectives of this paper are (1) to describe the design considerations and system architecture of a wrapper-mediator approach to federate search system design, including the use of knowledge-based, meta-search filters, and (2) to analyze the implications of system design choices on performance measurements. A trial was performed to evaluate the technical performance of a federated evidence retrieval system, which provided access to eight distinct online resources, including e-journals, PubMed, and electronic guidelines. The Quick Clinical system architecture utilized a universal query language to reformulate queries internally and utilized meta-search filters to optimize search strategies across resources. We recruited 227 family physicians from across Australia who used the system to retrieve evidence in a routine clinical setting over a 4-week period. The total search time for a query was recorded, along with the duration of individual queries sent to different online resources. Clinicians performed 1662 searches over the trial. The average search duration was 4.9 +/- 3.2 s (N = 1662 searches). Mean search duration to the individual sources was between 0.05 s and 4.55 s. Average system time (ie, system overhead) was 0.12 s. The relatively small system overhead compared to the average time it takes to perform a search for an individual source shows that the system achieves a good trade-off between performance and reliability. Furthermore, despite the additional effort required to incorporate the

  11. Architecture for Knowledge-Based and Federated Search of Online Clinical Evidence

    PubMed Central

    Walther, Martin; Nguyen, Ken; Lovell, Nigel H

    2005-01-01

    Background It is increasingly difficult for clinicians to keep up-to-date with the rapidly growing biomedical literature. Online evidence retrieval methods are now seen as a core tool to support evidence-based health practice. However, standard search engine technology is not designed to manage the many different types of evidence sources that are available or to handle the very different information needs of various clinical groups, who often work in widely different settings. Objectives The objectives of this paper are (1) to describe the design considerations and system architecture of a wrapper-mediator approach to federate search system design, including the use of knowledge-based, meta-search filters, and (2) to analyze the implications of system design choices on performance measurements. Methods A trial was performed to evaluate the technical performance of a federated evidence retrieval system, which provided access to eight distinct online resources, including e-journals, PubMed, and electronic guidelines. The Quick Clinical system architecture utilized a universal query language to reformulate queries internally and utilized meta-search filters to optimize search strategies across resources. We recruited 227 family physicians from across Australia who used the system to retrieve evidence in a routine clinical setting over a 4-week period. The total search time for a query was recorded, along with the duration of individual queries sent to different online resources. Results Clinicians performed 1662 searches over the trial. The average search duration was 4.9 ± 3.2 s (N = 1662 searches). Mean search duration to the individual sources was between 0.05 s and 4.55 s. Average system time (ie, system overhead) was 0.12 s. Conclusions The relatively small system overhead compared to the average time it takes to perform a search for an individual source shows that the system achieves a good trade-off between performance and reliability. Furthermore, despite

  12. Pharmacogenomics of Anti-platelet Therapy: How much evidence is enough for clinical implementation?

    PubMed Central

    Perry, Christina G.; Shuldiner, Alan R.

    2013-01-01

    Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Those who carry loss-of-function variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamics, and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will the astute clinician be able to use pharmacogenetic information in conjunction with the history, physical exam, and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient. PMID:23697979

  13. Clinical evidence of inflammation driving secondary brain injury: A systematic review

    PubMed Central

    Hinson, Holly E.; Rowell, Susan; Schreiber, Martin

    2015-01-01

    Background Despite advances in both prevention and treatment, traumatic brain injury (TBI) remains one of the most burdensome diseases; 2% of the US population currently lives with disabilities resulting from TBI. Recent advances in the understanding of inflammation and its impact on the pathophysiology of trauma have increased the interest in inflammation as a possible mediator in TBI outcome. Objectives The goal of this systematic review is to address the question: “What is the evidence in humans that inflammation is linked to secondary brain injury?” As the experimental evidence has been well described elsewhere, this review will focus on the clinical evidence for inflammation as a mechanism of secondary brain injury. Data Sources Medline database (1996-Week 1 June 2014), Pubmed and Google Scholar databases were queried for relevant studies. Study Eligibility Criteria Studies were eligible if participants were adults and/or children who sustained moderate or severe TBI in the acute phase of injury, published in English. Studies published in the last decade (since 2004) were preferentially included. Trials could be observational or interventional in nature. Appraisal and Synthesis Methods To address the quality of the studies retrieved, we applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria to assess the limitations of the included studies. Results Trauma initiates local central nervous system as well as systemic immune activation. Numerous observational studies describe elevation of pro-inflammatory cytokines that are associated with important clinical variables including neurologic outcome and mortality. A small number of clinical trials have included immunomodulating strategies, but no intervention to date has proven effective in improving outcomes after TBI. Limitations Inclusion of studies not initially retrieved by the search terms may have biased our results. Additionally, some reports may have been

  14. Defining post-sternotomy mediastinitis for clinical evidence-based studies.

    PubMed

    van Wingerden, Jan J; de Mol, Bas A J M; van der Horst, Chantal M A M

    2016-05-01

    Considerable advances have already been made in the treatment of deep thoracic wound infections following a median sternotomy for cardiac surgery. Further improvement in diagnosis, treatment, and outcome will require a targeted approach by multidisciplinary teams. Clear communication and synergy between the various clinical and supportive disciplines would assist in removing the last barriers to standardized evidence-based studies and the development of improved evidence-based guidelines. An extensive literature search without language restrictions was carried out on PubMed (Medline), EMBASE, and Web of Science, covering the period 1988 to week 16, 2014, and a manual search of the reference lists was performed regarding all possible definitions and classifications of post-sternotomy mediastinitis. Two hundred and eighteen papers describing post-sternotomy infections in a multitude of terms were identified, and the strengths and weaknesses of the most popular definitions and terms relating specifically to post-sternotomy infections were examined. This study revealed that clinicians use a multitude of terms to describe post-sternotomy infections without defining the condition under treatment. Occasionally, older epidemiological (surveillance) definitions were used. It also shows that supportive disciplines have their own definitions, or interpretations of existing definitions, to describe these infections. The outcome of this study is that clinicians have adopted no single definition, which is essential for further improvement for evidence-based studies. We suggest that it is possible to adopt a single term for thoracic infection after a sternotomy (and only sternotomy), and propose a clinical definition for this purpose. © The Author(s) 2016.

  15. Deleterious effects of neuronal accumulation of glycogen in flies and mice

    PubMed Central

    Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

    2012-01-01

    Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. PMID:22549942

  16. Developing evidence-based physical therapy clinical practice guidelines.

    PubMed

    Kaplan, Sandra L; Coulter, Colleen; Fetters, Linda

    2013-01-01

    Recommended strategies for developing evidence-based clinical practice guidelines (CPGs) are provided. The intent is that future CPGs developed with the support of the Section on Pediatrics of the American Physical Therapy Association would consistently follow similar developmental processes to yield consistent quality and presentation. Steps in the process of developing CPGs are outlined and resources are provided to assist CPG developers in carrying out their task. These recommended processes may also be useful to CPG developers representing organizations with similar structures, objectives, and resources.

  17. Large-scale adverse effects related to treatment evidence standardization (LAERTES): an open scalable system for linking pharmacovigilance evidence sources with clinical data.

    PubMed

    2017-03-07

    Integrating multiple sources of pharmacovigilance evidence has the potential to advance the science of safety signal detection and evaluation. In this regard, there is a need for more research on how to integrate multiple disparate evidence sources while making the evidence computable from a knowledge representation perspective (i.e., semantic enrichment). Existing frameworks suggest well-promising outcomes for such integration but employ a rather limited number of sources. In particular, none have been specifically designed to support both regulatory and clinical use cases, nor have any been designed to add new resources and use cases through an open architecture. This paper discusses the architecture and functionality of a system called Large-scale Adverse Effects Related to Treatment Evidence Standardization (LAERTES) that aims to address these shortcomings. LAERTES provides a standardized, open, and scalable architecture for linking evidence sources relevant to the association of drugs with health outcomes of interest (HOIs). Standard terminologies are used to represent different entities. For example, drugs and HOIs are represented in RxNorm and Systematized Nomenclature of Medicine -- Clinical Terms respectively. At the time of this writing, six evidence sources have been loaded into the LAERTES evidence base and are accessible through prototype evidence exploration user interface and a set of Web application programming interface services. This system operates within a larger software stack provided by the Observational Health Data Sciences and Informatics clinical research framework, including the relational Common Data Model for observational patient data created by the Observational Medical Outcomes Partnership. Elements of the Linked Data paradigm facilitate the systematic and scalable integration of relevant evidence sources. The prototype LAERTES system provides useful functionality while creating opportunities for further research. Future work will

  18. Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

    PubMed

    Le, Jimmy T; Hutfless, Susan; Li, Tianjing; Bressler, Neil M; Heyward, James; Bittner, Ava K; Glassman, Adam; Dickersin, Kay

    2017-01-01

    Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME). Cross-sectional study. Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators. We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions. Ranking of importance of each clinical question. Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review. A limited response rate among

  19. Experimental evidence of dietary ciguatoxin accumulation in an herbivorous coral reef fish.

    PubMed

    Clausing, Rachel J; Losen, Barbara; Oberhaensli, Francois R; Darius, H Taiana; Sibat, Manoella; Hess, Philipp; Swarzenski, Peter W; Chinain, Mireille; Dechraoui Bottein, Marie-Yasmine

    2018-07-01

    Ciguatoxins (CTXs) are potent algal toxins that cause widespread ciguatera poisoning and are found ubiquitously in coral reef food webs. Here we developed an environmentally-relevant, experimental model of CTX trophic transfer involving dietary exposure of herbivorous fish to the CTX-producing microalgae Gambierdiscus polynesiensis. Juvenile Naso brevirostris were fed a gel-food embedded with microalgae for 16 weeks (89 cells g -1 fish daily, 0.4 μg CTX3C equiv kg -1 fish). CTXs in muscle tissue were detectable after 2 weeks at levels above the threshold for human intoxication (1.2 ± 0.2 μg CTX3C equiv kg -1 ). Although tissue CTX concentrations stabilized after 8 weeks (∼3 ± 0.5 μg CTX3C equiv kg -1 ), muscle toxin burden (total μg CTX in muscle tissue) continued to increase linearly through the end of the experiment (16 weeks). Toxin accumulation was therefore continuous, yet masked by somatic growth dilution. The observed CTX concentrations, accumulation rates, and general absence of behavioural signs of intoxication are consistent with field observations and indicate that this method of dietary exposure may be used to develop predictive models of tissue-specific CTX uptake, metabolism and depuration. Results also imply that slow-growing fish may accumulate higher CTX flesh concentrations than fast-growing fish, which has important implications for global seafood safety. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Effect of clinically discriminating, evidence-based checklist items on the reliability of scores from an Internal Medicine residency OSCE.

    PubMed

    Daniels, Vijay J; Bordage, Georges; Gierl, Mark J; Yudkowsky, Rachel

    2014-10-01

    Objective structured clinical examinations (OSCEs) are used worldwide for summative examinations but often lack acceptable reliability. Research has shown that reliability of scores increases if OSCE checklists for medical students include only clinically relevant items. Also, checklists are often missing evidence-based items that high-achieving learners are more likely to use. The purpose of this study was to determine if limiting checklist items to clinically discriminating items and/or adding missing evidence-based items improved score reliability in an Internal Medicine residency OSCE. Six internists reviewed the traditional checklists of four OSCE stations classifying items as clinically discriminating or non-discriminating. Two independent reviewers augmented checklists with missing evidence-based items. We used generalizability theory to calculate overall reliability of faculty observer checklist scores from 45 first and second-year residents and predict how many 10-item stations would be required to reach a Phi coefficient of 0.8. Removing clinically non-discriminating items from the traditional checklist did not affect the number of stations (15) required to reach a Phi of 0.8 with 10 items. Focusing the checklist on only evidence-based clinically discriminating items increased test score reliability, needing 11 stations instead of 15 to reach 0.8; adding missing evidence-based clinically discriminating items to the traditional checklist modestly improved reliability (needing 14 instead of 15 stations). Checklists composed of evidence-based clinically discriminating items improved the reliability of checklist scores and reduced the number of stations needed for acceptable reliability. Educators should give preference to evidence-based items over non-evidence-based items when developing OSCE checklists.

  1. Clinical Evidence of Acute Mesoamerican Nephropathy.

    PubMed

    Fischer, Rebecca S B; Mandayam, Sreedhar; Chavarria, Denis; Vangala, Chandan; Nolan, Melissa S; Garcia, Linda L; Palma, Lesbia; Garcia, Felix; García-Trabanino, Ramón; Murray, Kristy O

    2017-10-01

    Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

  2. [Approaches, knowledge and capabilities of nurses and physicians regarding evidence-based clinical practice in the Imbadura province (Ecuador)].

    PubMed

    Molina Mula, Jesús; Muñoz Navarro, Paulina; Vaca Auz, Janeth; Cabascango Cabascango, Carmita; Cabascango Cabascango, Katty

    2015-01-01

    The research raises the need to increase understanding of organizational and personal factors that influence the attitude and aptitude of each professional, with respect to evidence-based clinical practice. The aim of this study is to describe the transfer of knowledge into clinical practice in hospital units in Imbabura (Ecuador) identifying the obstacles to implementing evidence-based clinical practice validated questionnaire EBPQ-19. A cross-sectional observational study was conducted in hospitals of the Ministry of Public Health of Imbabura of Ecuador took place, including a total of 281 nurses and physicians. Nurses and physicians showed positive attitudes toward evidence-based clinical practice (EBCP) and their use to support clinical decision-making. This research evidences perceptions of professionals on strategies for knowledge transfer and obstacles to carry it out. Significant differences between the perception of the use of EBCP strategies between nurses and physicians are observed. Physicians consider they use them frequently, while nurses acknowledge using them less (chi-square: 105.254, P=.018). In conclusion, we can say that these factors should be considered as necessary to improve the quality of care that is provided to users based on the best available evidence. It is necessary to start developing change interventions in this regard to remedy the current situation of clinical practice based not on evidence, but rather on experience only. Experimental studies demonstrating the effectiveness of strategies to eliminate barriers to scientific evidence-based clinical practice should be conducted. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  3. Quality of clinical and economic evidence in dossier formulary submissions.

    PubMed

    Colmenero, Fernando; Sullivan, Sean D; Palmer, Jennifer A; Brauer, Carmen A; Bungay, Kathleen; Watkins, John; Neumann, Peter J

    2007-07-01

    To investigate the quality and completeness of clinical and economic data in dossiers submitted by drug companies to a health plan using Academy of Managed Care Pharmacy guidelines (the Format) for formulary submissions. We reviewed the quality of economic analyses in dossiers submitted to Premera Blue Cross Health Plan (Mountlake Terrace, Washington; enrollment 1.6 million) between January 2002 and September 2005. For dossiers submitted in 2003, we examined the clinical studies included. Dossiers were audited with a data collection form to judge the types of clinical studies used to support labeled and off-label indications, and the quality and transparency of economic analyses. We compared economic analyses for high-cost (30-day treatment cost > $1000) versus low-cost products, and for "innovative" versus "me-too" drugs. Evidence to support off-label indications often was included in 2003 dossiers, but the information was less extensive and of poorer quality than data for labeled indications. Of 115 dossiers submitted between 2002 and 2005, 53 (46%) included economic analyses. The economic analyses had low levels of compliance with standards: only 43% performed sensitivity analysis; 38% stated the study perspective; 37% discussed relevant treatment alternatives; 20% stated assumptions clearly; and 18% mentioned caveats to conclusions. Economic analyses of high-cost products and innovative products had higher compliance with recommended practices. Drug companies are submitting dossiers of evidence to formulary committees. Dossiers often included clinical data to support off-label indications, but concerns persist about their quality. About half of dossiers included economic analyses, but these analyses had relatively low levels of compliance with recommended practices.

  4. Accumulation of Mutant Neuroserpin Precedes Development of Clinical Symptoms in Familial Encephalopathy with Neuroserpin Inclusion Bodies

    PubMed Central

    Galliciotti, Giovanna; Glatzel, Markus; Kinter, Jochen; Kozlov, Serguei V.; Cinelli, Paolo; Rülicke, Thomas; Sonderegger, Peter

    2007-01-01

    Intracellular protein deposition due to aggregation caused by conformational alteration is the hallmark of a number of neurodegenerative disorders, including Parkinson’s disease, tauopathies, Huntington’s disease, and familial encephalopathy with neuroserpin inclusion bodies. The latter is an autosomal dominant disorder caused by point mutations in neuroserpin resulting in its destabilization. Mutant neuroserpin polymerizes and forms intracellular aggregates that eventually lead to neurodegeneration. We generated genetically modified mice expressing the late-onset S49P-Syracuse or the early-onset S52R-Portland mutation of neuroserpin in central nervous system neurons. Mice exhibited morphological, biochemical, and clinical features resembling those found in the human disease. Analysis of brains revealed large intraneuronal inclusions composed exclusively of mutant neuroserpin, accumulating long before the development of clinical symptoms in a time-dependent manner. Clinical symptoms and amount of neuroserpin inclusions correlated with the predicted instability of the protein. The presence of inclusion bodies in subclinical mice indicates that in humans the prevalence of the disease could be higher than anticipated. In addition to shedding light on the pathophysiology of the human disorder, these mice provide an excellent model to study mechanisms of neurodegeneration or establish novel therapies for familial encephalopathy with neuroserpin inclusion bodies and other neurodegenerative diseases with intracellular protein deposition. PMID:17392169

  5. Measuring Clinical Decision Support Influence on Evidence-Based Nursing Practice.

    PubMed

    Cortez, Susan; Dietrich, Mary S; Wells, Nancy

    2016-07-01

    To measure the effect of clinical decision support (CDS) on oncology nurse evidence-based practice (EBP).
. Longitudinal cluster-randomized design.
. Four distinctly separate oncology clinics associated with an academic medical center.
. The study sample was comprised of randomly selected data elements from the nursing documentation software. The data elements were patient-reported symptoms and the associated nurse interventions. The total sample observations were 600, derived from a baseline, posteducation, and postintervention sample of 200 each (100 in the intervention group and 100 in the control group for each sample).
. The cluster design was used to support randomization of the study intervention at the clinic level rather than the individual participant level to reduce possible diffusion of the study intervention. An elongated data collection cycle (11 weeks) controlled for temporary increases in nurse EBP related to the education or CDS intervention.
. The dependent variable was the nurse evidence-based documentation rate, calculated from the nurse-documented interventions. The independent variable was the CDS added to the nursing documentation software.
. The average EBP rate at baseline for the control and intervention groups was 27%. After education, the average EBP rate increased to 37%, and then decreased to 26% in the postintervention sample. Mixed-model linear statistical analysis revealed no significant interaction of group by sample. The CDS intervention did not result in an increase in nurse EBP.
. EBP education increased nurse EBP documentation rates significantly but only temporarily. Nurses may have used evidence in practice but may not have documented their interventions.
. More research is needed to understand the complex relationship between CDS, nursing practice, and nursing EBP intervention documentation. CDS may have a different effect on nurse EBP, physician EBP, and other medical professional EBP.

  6. Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

    PubMed

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

    2016-05-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

  7. Vitamin D and Colorectal Cancer: Molecular, Epidemiological, and Clinical Evidence

    PubMed Central

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L.; Manson, JoAnn E.; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

  8. Energy-Dependent Accumulation of Fluoroquinolones in Quinolone-Resistant Klebsiella pneumoniae Strains

    PubMed Central

    Martínez-Martínez, Luis; García, Isabel; Ballesta, Sofía; Benedí, Vicente Javier; Hernández-Allés, Santiago; Pascual, Alvaro

    1998-01-01

    The intracellular accumulation of norfloxacin and pefloxacin in Klebsiella pneumoniae was evaluated. The roles of lipopolysaccharide, capsule, and outer membrane proteins were not important for the intrabacterial accumulation of fluoroquinolones in isogenic strains with known outer membrane alterations. In fluoroquinolone-resistant clinical isolates also expressing GyrA alterations, an active efflux leading to decreased accumulation of the drugs enhanced their resistance to these agents. PMID:9661034

  9. Integrating evidence-based teaching into to clinical practice should improve outcomes.

    PubMed

    Richards, Derek

    2005-01-01

    Sources used were Medline, Embase, the Education Resources Information Centre , Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Best Evidence, Best Evidence Medical Education and Science Citation Index, along with reference lists of known systematic reviews. Studies were chosen for inclusion if they evaluated the effects of postgraduate evidence-based medicine (EBM) or critical appraisal teaching in comparison with a control group or baseline before teaching, using a measure of participants' learning achievements or patients' health gains as outcomes. Articles were graded as either level 1 (randomised controlled trials (RCT)) or level 2 (non-randomised studies that either had a comparison with a control group), or a before and after comparison without a control group. Learning achievement was assessed separately for knowledge, critical appraisal skills, attitudes and behaviour. Because of obvious heterogeneity in the features of individual studies, their quality and assessment tools used, a meta-analysis could not be carried out. Conclusions were weighted by methodological quality. Twenty-three relevant studies were identified, comprising four RCT, seven non-RCT, and 12 before and after comparison studies. Eighteen studies (including two RCT) evaluated a standalone teaching method and five studies (including two RCT) evaluated a clinically integrated teaching method. Standalone teaching improved knowledge but not skills, attitudes or behaviour. Clinically integrated teaching improved knowledge, skills, attitudes and behaviour. Teaching of EBM should be moved from classrooms to clinical practice to achieve improvements in substantial outcomes.

  10. Deleterious effects of neuronal accumulation of glycogen in flies and mice.

    PubMed

    Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

    2012-08-01

    Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. Copyright © 2012 EMBO Molecular Medicine.

  11. Vitamin K status and vascular calcification: evidence from observational and clinical studies.

    PubMed

    Shea, M Kyla; Holden, Rachel M

    2012-03-01

    Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.

  12. Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

    PubMed

    Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

    2015-10-01

    The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

  13. Integration of Evidence into a Detailed Clinical Model-based Electronic Nursing Record System

    PubMed Central

    Park, Hyeoun-Ae; Jeon, Eunjoo; Chung, Eunja

    2012-01-01

    Objectives The purpose of this study was to test the feasibility of an electronic nursing record system for perinatal care that is based on detailed clinical models and clinical practice guidelines in perinatal care. Methods This study was carried out in five phases: 1) generating nursing statements using detailed clinical models; 2) identifying the relevant evidence; 3) linking nursing statements with the evidence; 4) developing a prototype electronic nursing record system based on detailed clinical models and clinical practice guidelines; and 5) evaluating the prototype system. Results We first generated 799 nursing statements describing nursing assessments, diagnoses, interventions, and outcomes using entities, attributes, and value sets of detailed clinical models for perinatal care which we developed in a previous study. We then extracted 506 recommendations from nine clinical practice guidelines and created sets of nursing statements to be used for nursing documentation by grouping nursing statements according to these recommendations. Finally, we developed and evaluated a prototype electronic nursing record system that can provide nurses with recommendations for nursing practice and sets of nursing statements based on the recommendations for guiding nursing documentation. Conclusions The prototype system was found to be sufficiently complete, relevant, useful, and applicable in terms of content, and easy to use and useful in terms of system user interface. This study has revealed the feasibility of developing such an ENR system. PMID:22844649

  14. N-acetylcysteine in contrast-induced acute kidney injury: clinical use against principles of evidence-based clinical medicine!

    PubMed

    Sadat, Umar

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is one of the most widely discussed and debated topic in cardiovascular medicine and N-acetylcysteine (NAC) is the most widely used pharmacological agent assessed in clinical trials for offering renal protection against CI-AKI. Results of these clinical trials are though split between those that favor its use and vice versa. In this brief communication we discuss the latest research advances regarding the use of NAC against CI-AKI. Recent clinical evidence and overview of in-depth statistical analyses of relevant clinical trials and their meta-analyses do not support the use of NAC in prophylaxis against CI-AKI. Adequate hydration before and after contrast media exposure, along with avoidance of nephrotoxic drugs, remains the recommended prophylaxis against CI-AKI.

  15. The context & clinical evidence for common nursing practices during labor.

    PubMed

    Simpson, Kathleen Rice

    2005-01-01

    The purpose of this article is to review the context and current evidence for common nursing care practices during labor and birth. Although many nursing interventions during labor and birth are based on physician orders, there are a number of care processes that are mainly within the realm of nursing practice. In many cases, particularly in community hospitals, routine physician orders for intrapartum care provide wide latitude for nurses in how they ultimately carry out those orders. An important consideration of common nursing practices during labor is the context or practice model in which those practices occur. Nursing practice is not the same in all clinical environments. Intrapartum nursing practice consists of an assortment of different roles depending on the circumstances, hospital setting, and context in which it takes place. A variety of intrapartum nursing practice models have evolved as a result and in response to the range of sizes, locations, and provider practice styles found in hospitals providing obstetric services. A summary of intrapartum nursing models is presented. The evidence is reviewed for the three most common clinical practices for which nurses have primary responsibility in most settings and that comprise the majority of their time in caring for women during labor: (1) maternal-fetal assessment, (2) management of oxytocin infusions, and (3) second-stage care. Evidence exists for these nursing interventions that can be used to promote maternal-fetal well-being, minimize risk, and enhance patient safety.

  16. Recent Clinical Drug Trials Evidence in Marfan Syndrome and Clinical Implications.

    PubMed

    Singh, Michael N; Lacro, Ronald V

    2016-01-01

    Marfan syndrome is a genetic disorder of connective tissue with principal manifestations in the cardiovascular, ocular, and skeletal systems. Cardiovascular disease, mainly progressive aortic root dilation and aortic dissection, is the leading cause of morbidity and mortality. The primary aims of this report were to examine the evidence related to medical therapy for Marfan syndrome, including recently completed randomized clinical trials on the efficacy of β-blockers and angiotensin II receptor blockers for the prophylactic treatment of aortic enlargement in Marfan syndrome, and to provide recommendations for medical therapy on the basis of available evidence. Medical therapy for Marfan syndrome should be individualized according to patient tolerance and risk factors such as age, aortic size, and family history of aortic dissection. The Pediatric Heart Network trial showed that atenolol and losartan each reduced the rate of aortic dilation. All patients with known or suspected Marfan syndrome and aortic root dilation should receive medical therapy with adequate doses of either β-blocker or angiotensin receptor blocker. The Pediatric Heart Network trial also showed that atenolol and losartan are more effective at reduction of aortic root z score in younger subjects, which suggests that medical therapy should be prescribed even in the youngest children with aortic dilation. For patients with Marfan syndrome without aortic dilation, the available evidence is less clear. If aortic dilation is severe and/or progressive, therapy with a combination of β-blocker and angiotensin receptor blocker should be considered, although trial results are mixed with respect to the efficacy of combination therapy vs monotherapy. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  17. Using an evidence-based approach to measure outcomes in clinical practice.

    PubMed

    MacDermid, Joy C; Grewal, Ruby; MacIntyre, Norma J

    2009-02-01

    Evaluation of the outcome of evidence-based practice decisions in individual patients or patient groups is step five in the evidence-based practice approach. Outcome measures are any measures that reflect patient status. Status or outcome measures can be used to detect change over time (eg, treatment effects), to discriminate among clinical groups, or to predict future outcomes (eg, return to work). A variety of reliable and valid physical impairment and disability measures are available to assess treatment outcomes in hand surgery and therapy. Evidence from research studies that includes normative data, standard error of measurement, or comparative scores for important clinical subgroups can be used to set treatment goals, monitor recovery, and compare individual patient outcomes to those reported in the literature. Clinicians tend to rely on impairment measures, such as radiographic measures, grip strength, and range of motion, although self-report measures are known to be equally reliable and more related to global effects, such as return-to-work. The process of selecting and implementing outcome measures is crucial. This process works best when team members are involved and willing to trial new measures. In this way, the team can develop customized outcome assessment procedures that meet their needs for assessing individual patients and providing data for program evaluation.

  18. Treatment-resistant Schizophrenia: Evidence-based Strategies

    PubMed Central

    Englisch, Susanne; Zink, Mathias

    2012-01-01

    Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. PMID:22654380

  19. Evidence in clinical reasoning: a computational linguistics analysis of 789,712 medical case summaries 1983-2012.

    PubMed

    Seidel, Bastian M; Campbell, Steven; Bell, Erica

    2015-03-21

    Better understanding of clinical reasoning could reduce diagnostic error linked to 8% of adverse medical events and 30% of malpractice cases. To a greater extent than the evidence-based movement, the clinical reasoning literature asserts the importance of practitioner intuition—unconscious elements of diagnostic reasoning. The study aimed to analyse the content of case report summaries in ways that explored the importance of an evidence concept, not only in relation to research literature but also intuition. The study sample comprised all 789,712 abstracts in English for case reports contained in the database PUBMED for the period 1 January 1983 to 31 December 2012. It was hypothesised that, if evidence and intuition concepts were viewed by these clinical authors as essential to understanding their case reports, they would be more likely to be found in the abstracts. Computational linguistics software was used in 1) concept mapping of 21,631,481 instances of 201 concepts, and 2) specific concept analyses examining 200 paired co-occurrences for 'evidence' and research 'literature' concepts. 'Evidence' is a fundamentally patient-centred, intuitive concept linked to less common concepts about underlying processes, suspected disease mechanisms and diagnostic hunches. In contrast, the use of research literature in clinical reasoning is linked to more common reasoning concepts about specific knowledge and descriptions or presenting features of cases. 'Literature' is by far the most dominant concept, increasing in relevance since 2003, with an overall relevance of 13% versus 5% for 'evidence' which has remained static. The fact that the least present types of reasoning concepts relate to diagnostic hunches to do with underlying processes, such as what is suspected, raises questions about whether intuitive practitioner evidence-making, found in a constellation of dynamic, process concepts, has become less important. The study adds support to the existing corpus of

  20. Clinical evidence inputs to comparative effectiveness research could impact the development of novel treatments.

    PubMed

    Eber, Michael R; Goldman, Dana P; Lakdawalla, Darius N; Philipson, Tomas J; Pritchard, Daryl; Huesch, Marco; Summers, Nicholas; Linthicum, Mark T; Sullivan, Jeff; Dubois, Robert W

    2015-05-07

    This study aims to analyze the impacts of a range of clinical evidence generation scenarios associated with comparative effectiveness research (CER) on pharmaceutical innovation. We used the Global Pharmaceutical Policy Model to project the effect of changes in pharmaceutical producer costs, revenues and timings on drug innovation and health for the age 55+ populations in the USA and Europe through year 2060 using three clinical scenarios. Changes in producer incentives from widespread CER evidence generation and use had varied but often large predicted impacts on simulated outcomes in 2060. Effect on the number of new drug introductions ranged from a 81.1% reduction to a 45.5% increase, and the effect on population-level life expectancy ranged from a 15.6% reduction to a 11.4% increase compared to baseline estimates. The uncertainty surrounding the consequences of increased clinical evidence generation and use on innovation calls for a carefully measured approach to CER implementation, balancing near-term benefits to spending and health with long-term implications for innovation.

  1. What should we mean by empirical validation in hypnotherapy: evidence-based practice in clinical hypnosis.

    PubMed

    Alladin, Assen; Sabatini, Linda; Amundson, Jon K

    2007-04-01

    This paper briefly surveys the trend of and controversy surrounding empirical validation in psychotherapy. Empirical validation of hypnotherapy has paralleled the practice of validation in psychotherapy and the professionalization of clinical psychology, in general. This evolution in determining what counts as evidence for bona fide clinical practice has gone from theory-driven clinical approaches in the 1960s and 1970s through critical attempts at categorization of empirically supported therapies in the 1990s on to the concept of evidence-based practice in 2006. Implications of this progression in professional psychology are discussed in the light of hypnosis's current quest for validation and empirical accreditation.

  2. An Update on Accumulating Exercise and Postprandial Lipaemia: Translating Theory Into Practice

    PubMed Central

    Burns, Stephen F; Stensel, David J

    2013-01-01

    Over the last two decades, significant research attention has been given to the acute effect of a single bout of exercise on postprandial lipaemia. A large body of evidence supports the notion that an acute bout of aerobic exercise can reduce postprandial triacylglycerol (TAG) concentrations. However, this effect is short-lived emphasising the important role of regular physical activity for lowering TAG concentrations through an active lifestyle. In 1995, the concept of accumulating physical activity was introduced in expert recommendations with the advice that activity can be performed in several short bouts throughout the day with a minimum duration of 10 minutes per activity bout. Although the concept of accumulation has been widely publicised, there is still limited scientific evidence to support it but several studies have investigated the effects of accumulated activity on health-related outcomes to support the recommendations in physical activity guidelines. One area, which is the focus of this review, is the effect of accumulating exercise on postprandial lipaemia. We propose that accumulating exercise will provide additional physical activity options for lowering postprandial TAG concentrations relevant to individuals with limited time or exercise capacity to engage in more structured forms of exercise, or longer bouts of physical activity. The benefits of accumulated physical activity might translate to a reduced risk of cardiovascular disease in the long-term. PMID:23412842

  3. Amyloid and intracellular accumulation of BRI2.

    PubMed

    Garringer, Holly J; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

    2017-04-01

    Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI 2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI 2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI 2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI 2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI 2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI 2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI 2 in the pathogenesis of FBD and FDD and implicates BRI 2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Amyloid and intracellular accumulation of BRI2

    PubMed Central

    Garringer, Holly J.; Sammeta, Neeraja; Oblak, Adrian; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2 in the pathogenesis of FBD and FDD and implicates BRI2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. PMID:28131015

  5. Linking Essential Tremor to the Cerebellum: Clinical Evidence.

    PubMed

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways.

  6. Improving the Implementation of Evidence-Based Clinical Practices in Adolescent Reproductive Health Care Services

    PubMed Central

    Romero, Lisa M.; Middleton, Dawn; Mueller, Trisha; Avellino, Lia; Hallum-Montes, Rachel

    2015-01-01

    Purpose The purposes of the study were to describe baseline data in the implementation of evidence-based clinical practices among health center partners as part of a community-wide teen pregnancy prevention initiative and to identify opportunities for health center improvement. Methods Health center partner baseline data were collected in the first year (2011) and before program implementation of a 5-year community-wide teen pregnancy prevention initiative. A needs assessment on health center capacity and implementation of evidence-based clinical practices was administered with 51 health centers partners in 10 communities in the United States with high rates of teen pregnancy. Results Health centers reported inconsistent implementation of evidence-based clinical practices in providing reproductive health services to adolescents. Approximately 94.1% offered same-day appointments, 91.1% had infrastructure to reduce cost barriers, 90.2% offered after-school appointments, and 80.4% prescribed hormonal contraception without prerequisite examinations or testing. Approximately three quarters provided visual and audio privacy in examination rooms (76.5%) and counseling areas (74.5%). Fewer offered a wide range of contraceptive methods (67.8%) and took a sexual health history at every visit (54.9%). Only 45.1% reported Quick Start initiation of hormonal contraception, emergency contraception (43.1%), or intrauterine devices (12.5%) were “always” available to adolescents. Conclusions The assessment highlighted opportunities for health center improvement. Strategies to build capacity of health center partners to implement evidence-based clinical practices may lead to accessibility and quality of reproductive health services for adolescents in the funded communities. PMID:26381918

  7. Evidence of clinical utility: an unmet need in molecular diagnostics for patients with cancer.

    PubMed

    Parkinson, David R; McCormack, Robert T; Keating, Susan M; Gutman, Steven I; Hamilton, Stanley R; Mansfield, Elizabeth A; Piper, Margaret A; Deverka, Patricia; Frueh, Felix W; Jessup, J Milburn; McShane, Lisa M; Tunis, Sean R; Sigman, Caroline C; Kelloff, Gary J

    2014-03-15

    This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

  8. CE: Original Research: Creating an Evidence-Based Progression for Clinical Advancement Programs.

    PubMed

    Burke, Kathleen G; Johnson, Tonya; Sites, Christine; Barnsteiner, Jane

    2017-05-01

    : Background: The Institute of Medicine (IOM) and the Quality and Safety Education for Nurses (QSEN) project have identified six nursing competencies and supported their integration into undergraduate and graduate nursing curricula nationwide. But integration of those competencies into clinical practice has been limited, and evidence for the progression of competency proficiency within clinical advancement programs is scant. Using an evidence-based approach and building on the competencies identified by the IOM and QSEN, a team of experts at an academic health system developed eight competency domains and 186 related knowledge, skills, and attitudes (KSAs) for professional nursing practice. The aim of our study was to validate the eight identified competencies and 186 related KSAs and determine their developmental progression within a clinical advancement program. Using the Delphi technique, nursing leadership validated the newly identified competency domains and KSAs as essential to practice. Clinical experts from 13 Magnet-designated hospitals with clinical advancement programs then participated in Delphi rounds aimed at reaching consensus on the developmental progression of the 186 KSAs through four levels of clinical advancement. Two Delphi rounds resulted in consensus by the expert participants. All eight competency domains were determined to be essential at all four levels of clinical practice. At the novice level of practice, the experts identified a greater number of KSAs in the domains of safety and patient- and family-centered care. At more advanced practice levels, the experts identified a greater number of KSAs in the domains of professionalism, teamwork, technology and informatics, and continuous quality improvement. Incorporating the eight competency domains and the 186 KSAs into a framework for clinical advancement programs will likely result in more clearly defined role expectations; enhance accountability; and elevate and promote nursing practice

  9. Bipolar disorder and complementary medicine: current evidence, safety issues, and clinical considerations.

    PubMed

    Sarris, Jerome; Lake, James; Hoenders, Rogier

    2011-10-01

    Bipolar disorder (BD) is a debilitating syndrome that is often undiagnosed and undertreated. Population surveys show that persons with BD often self-medicate with complementary and alternative medicine (CAM) or integrative therapies in spite of limited research evidence supporting their use. To date, no review has focused specifically on nonconventional treatments of BD. The study objectives were to present a review of nonconventional (complementary and integrative) interventions examined in clinical trials on BD, and to offer provisional guidelines for the judicious integrative use of CAM in the management of BD. PubMed, CINAHL,(®) Web of Science, and Cochrane Library databases were searched for human clinical trials in English during mid-2010 using Bipolar Disorder and CAM therapy and CAM medicine search terms. Effect sizes (Cohen's d) were also calculated where data were available. Several positive high-quality studies on nutrients in combination with conventional mood stabilizers and antipsychotic medications in BD depression were identified, while branched-chain amino acids and magnesium were effective (small studies) in attenuating mania in BD. In the treatment of bipolar depression, evidence was mixed regarding omega-3, while isolated studies provide provisional support for a multinutrient formula, n-acetylcysteine, and l-tryptophan. In one study, acupuncture was found to have favorable but nonsignificant effects on mania and depression outcomes. Current evidence supports the integrative treatment of BD using combinations of mood stabilizers and select nutrients. Other CAM or integrative modalities used to treat BD have not been adequately explored to date; however, some early findings are promising. Select CAM and integrative interventions add to established conventional treatment of BD and may be considered when formulating a treatment plan. It is hoped that the safety issues and clinical considerations addressed in this article may encourage the practice

  10. A rapid evidence-based service by librarians provided information to answer primary care clinical questions.

    PubMed

    McGowan, Jessie; Hogg, William; Rader, Tamara; Salzwedel, Doug; Worster, Danielle; Cogo, Elise; Rowan, Margo

    2010-03-01

    A librarian consultation service was offered to 88 primary care clinicians during office hours. This included a streamlined evidence-based process to answer questions in fewer than 20 min. This included a contact centre accessed through a Web-based platform and using hand-held devices and computers with Web access. Librarians were given technical training in evidence-based medicine, including how to summarise evidence. To describe the process and lessons learned from developing and operating a rapid response librarian consultation service for primary care clinicians. Evaluation included librarian interviews and a clinician exit satisfaction survey. Clinicians were positive about its impact on their clinical practice and decision making. The project revealed some important 'lessons learned' in the clinical use of hand-held devices, knowledge translation and training for clinicians and librarians. The Just-in-Time Librarian Consultation Service showed that it was possible to provide evidence-based answers to clinical questions in 15 min or less. The project overcame a number of barriers using innovative solutions. There are many opportunities to build on this experience for future joint projects of librarians and healthcare providers.

  11. How Awareness Changes the Relative Weights of Evidence During Human Decision-Making

    PubMed Central

    Lamme, Victor A. F.; Dehaene, Stanislas

    2011-01-01

    Human decisions are based on accumulating evidence over time for different options. Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information? We examined the influence of awareness on decision-making using combined behavioral methods and magneto-encephalography (MEG). Participants were required to make decisions by accumulating evidence over a series of visually presented arrow stimuli whose visibility was modulated by masking. Behavioral results showed that participants could accumulate evidence under both high and low visibility. However, a top-down strategic modulation of the flow of incoming evidence was only present for stimuli with high visibility: once enough evidence had been accrued, participants strategically reduced the impact of new incoming stimuli. Also, decision-making speed and confidence were strongly modulated by the strength of the evidence for high-visible but not low-visible evidence, even though direct priming effects were identical for both types of stimuli. Neural recordings revealed that, while initial perceptual processing was independent of visibility, there was stronger top-down amplification for stimuli with high visibility than low visibility. Furthermore, neural markers of evidence accumulation over occipito-parietal cortex showed a strategic bias only for highly visible sensory information, speeding up processing and reducing neural computations related to the decision process. Our results indicate that the level of awareness of information changes decision-making: while accumulation of evidence already exists under low visibility conditions, high visibility allows evidence to be accumulated up to a higher level, leading to important strategical top-down changes in decision-making. Our results therefore suggest a potential role of awareness in deploying flexible strategies for biasing information acquisition in line with one's expectations and goals. PMID:22131904

  12. How awareness changes the relative weights of evidence during human decision-making.

    PubMed

    de Lange, Floris P; van Gaal, Simon; Lamme, Victor A F; Dehaene, Stanislas

    2011-11-01

    Human decisions are based on accumulating evidence over time for different options. Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information? We examined the influence of awareness on decision-making using combined behavioral methods and magneto-encephalography (MEG). Participants were required to make decisions by accumulating evidence over a series of visually presented arrow stimuli whose visibility was modulated by masking. Behavioral results showed that participants could accumulate evidence under both high and low visibility. However, a top-down strategic modulation of the flow of incoming evidence was only present for stimuli with high visibility: once enough evidence had been accrued, participants strategically reduced the impact of new incoming stimuli. Also, decision-making speed and confidence were strongly modulated by the strength of the evidence for high-visible but not low-visible evidence, even though direct priming effects were identical for both types of stimuli. Neural recordings revealed that, while initial perceptual processing was independent of visibility, there was stronger top-down amplification for stimuli with high visibility than low visibility. Furthermore, neural markers of evidence accumulation over occipito-parietal cortex showed a strategic bias only for highly visible sensory information, speeding up processing and reducing neural computations related to the decision process. Our results indicate that the level of awareness of information changes decision-making: while accumulation of evidence already exists under low visibility conditions, high visibility allows evidence to be accumulated up to a higher level, leading to important strategical top-down changes in decision-making. Our results therefore suggest a potential role of awareness in deploying flexible strategies for biasing information acquisition in line with one's expectations and goals.

  13. Comparison of Alternative Evidence Summary and Presentation Formats in Clinical Guideline Development: A Mixed-Method Study

    PubMed Central

    Opiyo, Newton; Shepperd, Sasha; Musila, Nyokabi; Allen, Elizabeth; Nyamai, Rachel; Fretheim, Atle; English, Mike

    2013-01-01

    Background Best formats for summarising and presenting evidence for use in clinical guideline development remain less well defined. We aimed to assess the effectiveness of different evidence summary formats to address this gap. Methods Healthcare professionals attending a one-week Kenyan, national guideline development workshop were randomly allocated to receive evidence packaged in three different formats: systematic reviews (SRs) alone, systematic reviews with summary-of-findings tables, and ‘graded-entry’ formats (a ‘front-end’ summary and a contextually framed narrative report plus the SR). The influence of format on the proportion of correct responses to key clinical questions, the primary outcome, was assessed using a written test. The secondary outcome was a composite endpoint, measured on a 5-point scale, of the clarity of presentation and ease of locating the quality of evidence for critical neonatal outcomes. Interviews conducted within two months following completion of trial data collection explored panel members’ views on the evidence summary formats and experiences with appraisal and use of research information. Results 65 (93%) of 70 participants completed questions on the prespecified outcome measures. There were no differences between groups in the odds of correct responses to key clinical questions. ‘Graded-entry’ formats were associated with a higher mean composite score for clarity and accessibility of information about the quality of evidence for critical neonatal outcomes compared to systematic reviews alone (adjusted mean difference 0.52, 95% CI 0.06 to 0.99). There was no difference in the mean composite score between SR with SoF tables and SR alone. Findings from interviews with 16 panelists indicated that short narrative evidence reports were preferred for the improved clarity of information presentation and ease of use. Conclusions Our findings suggest that ‘graded-entry’ evidence summary formats may improve clarity and

  14. Applying evidence-based management to anorexia nervosa.

    PubMed

    Treasure, Janet

    2016-09-01

    This paper considers how the three principles of evidence based practice (clinical expertise, scientific evidence, and patient preference) can be applied to the complexity of treatment for anorexia nervosa AN. A narrative review of the evidence of these three domains is presented. Clinical cases are used to illustrate how the formulation and management can be put into practice at different stages of illness. The management of anorexia nervosa is complex. First, individuals with the illness do not regard the manifestations of the illness as a source of concern rather they are embraced and integrated into their identity. This contrasts to the reaction of other people who are terrified by the overt signs of ill health. Thus engagement into treatment is problematic. Second, the core symptom restricted eating, produces malnutrition which impacts on brain, body, and the social network. Thus a mixture of psychological and physical problems gradually accumulates over the course of the illness. This means that the treatment targets increase over time. Thus treatment has to work with motivation and readiness to change and tackle the various domains of ill health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Assessing young children's intention-reading in authentic communicative contexts: preliminary evidence and clinical utility.

    PubMed

    Greenslade, Kathryn J; Coggins, Truman E

    2014-01-01

    Identifying what a communication partner is looking at (referential intention) and why (social intention) is essential to successful social communication, and may be challenging for children with social communication deficits. This study explores a clinical task that assesses these intention-reading abilities within an authentic context. To gather evidence of the task's reliability and validity, and to discuss its clinical utility. The intention-reading task was administered to twenty 4-7-year-olds with typical development (TD) and ten with autism spectrum disorder (ASD). Task items were embedded in an authentic activity, and they targeted the child's ability to identify the examiner's referential and social intentions, which were communicated through joint attention behaviours. Reliability and construct validity evidence were addressed using established psychometric methods. Reliability and validity evidence supported the use of task scores for identifying children whose intention-reading warranted concern. Evidence supported the reliability of task administration and coding, and item-level codes were highly consistent with overall task performance. Supporting task validity, group differences aligned with predictions, with children with ASD exhibiting poorer and more variable task scores than children with TD. Also, as predicted, task scores correlated significantly with verbal mental age and ratings of parental concerns regarding social communication abilities. The evidence provides preliminary support for the reliability and validity of the clinical task's scores in assessing young children's real-time intention-reading abilities, which are essential for successful interactions in school and beyond. © 2014 Royal College of Speech and Language Therapists.

  16. An Evidence-Based Practice Model across the Academic and Clinical Settings

    ERIC Educational Resources Information Center

    Wolter, Julie A.; Corbin-Lewis, Kim; Self, Trisha; Elsweiler, Anne

    2011-01-01

    This tutorial is designed to provide academic communication sciences and disorders (CSD) programs, at both the undergraduate and graduate levels, with a comprehensive instructional model on evidence-based practice (EBP). The model was designed to help students view EBP as an ongoing process needed in all clinical decision making. The three facets…

  17. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence.

    PubMed

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J Luis

    2016-08-09

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

  18. The attitude of Belgian social insurance physicians towards evidence-based practice and clinical practice guidelines.

    PubMed

    Heselmans, Annemie; Donceel, Peter; Aertgeerts, Bert; Van de Velde, Stijn; Ramaekers, Dirk

    2009-09-09

    Evidence-based medicine has broadened its scope and is starting to reach insurance medicine. Although still in its initial stages, physicians in the area of insurance medicine should keep up-to-date with the evidence on various diseases in order to correctly assess disability and to give appropriate advice about health care reimbursement. In order to explore future opportunities of evidence-based medicine to improve daily insurance medicine, there is a need for qualitative studies to better understand insurance physicians' perceptions of EBM. The present study was designed to identify the attitude of insurance physicians towards evidence-based medicine and clinical practice guidelines, and to determine their ability to access, retrieve and appraise the health evidence and the barriers for applying evidence to practice. A cross-sectional survey study was carried out among all Dutch-speaking insurance physicians employed at one of the six Belgian social insurance sickness funds and at the National Institute of Disability and Health care Insurance (n = 224). Chi-square tests were used to compare nominal and ordinal variables. Student's t-tests, ANOVA, Mann-Whitney and Kruskal-Wallis were used to compare means of continuous variables for different groups. The response rate was 48.7%. The majority of respondents were positive towards evidence-based medicine and clinical practice guidelines. Their knowledge of EBM was rather poor. Perceived barriers for applying evidence to practice were mainly time and lack of EBM skills. Although the majority of physicians were positive towards EBM and welcomed more guidelines, the use of evidence and clinical practice guidelines in insurance medicine is low at present. It is in the first place important to eradicate the perceived inertia which limits the use of EBM and to further investigate the EBM principles in the context of insurance medicine. Available high-quality evidence-based resources (at the moment mainly originating from

  19. The attitude of Belgian social insurance physicians towards evidence-based practice and clinical practice guidelines

    PubMed Central

    Heselmans, Annemie; Donceel, Peter; Aertgeerts, Bert; Van de Velde, Stijn; Ramaekers, Dirk

    2009-01-01

    Background Evidence-based medicine has broadened its scope and is starting to reach insurance medicine. Although still in its initial stages, physicians in the area of insurance medicine should keep up-to-date with the evidence on various diseases in order to correctly assess disability and to give appropriate advice about health care reimbursement. In order to explore future opportunities of evidence-based medicine to improve daily insurance medicine, there is a need for qualitative studies to better understand insurance physicians' perceptions of EBM. The present study was designed to identify the attitude of insurance physicians towards evidence-based medicine and clinical practice guidelines, and to determine their ability to access, retrieve and appraise the health evidence and the barriers for applying evidence to practice. Methods A cross-sectional survey study was carried out among all Dutch-speaking insurance physicians employed at one of the six Belgian social insurance sickness funds and at the National Institute of Disability and Health care Insurance (n = 224). Chi-square tests were used to compare nominal and ordinal variables. Student's t-tests, ANOVA, Mann-Whitney and Kruskal-Wallis were used to compare means of continuous variables for different groups. Results The response rate was 48.7%. The majority of respondents were positive towards evidence-based medicine and clinical practice guidelines. Their knowledge of EBM was rather poor. Perceived barriers for applying evidence to practice were mainly time and lack of EBM skills. Conclusion Although the majority of physicians were positive towards EBM and welcomed more guidelines, the use of evidence and clinical practice guidelines in insurance medicine is low at present. It is in the first place important to eradicate the perceived inertia which limits the use of EBM and to further investigate the EBM principles in the context of insurance medicine. Available high-quality evidence-based resources

  20. Clinical Evidence of Exercise Benefits for Stroke.

    PubMed

    Han, Peipei; Zhang, Wen; Kang, Li; Ma, Yixuan; Fu, Liyuan; Jia, Liye; Yu, Hairui; Chen, Xiaoyu; Hou, Lin; Wang, Lu; Yu, Xing; Kohzuki, Masahiro; Guo, Qi

    2017-01-01

    Even though stroke is the third, not the first, most common cause of disability-adjusted life years in developed countries, it is one of the most expensive to treat. Part of the expense is due to secondary problems in the post-stroke period including: cognition, memory, attention span, pain, sensation loss, psychological issues, and problems with mobility and balance. Research has identified that exercise has both positive physical and psychosocial effects for post-stroke patients. Therefore, this scientific statement provides an overview on exercise rehabilitation for post-stroke patients.We will use systematic literature reviews, clinical and epidemiology reports, published morbidity and mortality studies, clinical and public health guidelines, patient files, and authoritative statements to support this overview.Evidence clearly supports the use of various kinds of exercise training (e.g., aerobic, strength, flexibility, neuromuscular, and traditional Chinese exercise) for stroke survivors. Aerobic exercise, the main form of cardiac rehabilitation, may play an important role in improving aerobic fitness, cardiovascular fitness, cognitive abilities, walking speed and endurance, balance, quality of life, mobility, and other health outcomes among stroke patients. Strength exercise, included in national stroke guidelines and recommended for general health promotion for stroke survivors, can lead to improvements in functionality, psychosocial aspects, and quality of life for post-stroke patients. Flexibility exercises can relieve muscle spasticity problems, improve motor function, range of motion, and prevent contractures. Stretching exercises can also prevent joint contractures, muscle shortening, decrease spasticity, reduce joint stiffness and improve a post-stroke patient's overall function. Neuromuscular exercises can improve activities of daily living (ADL) through coordination and balance activities. Traditional Chinese exercises are used to improve walking and

  1. Clinical Evidence in Guardianship of Older Adults Is Inadequate: Findings From a Tri-State Study

    PubMed Central

    Moye, Jennifer; Wood, Stacey; Edelstein, Barry; Armesto, Jorge C.; Bower, Emily H.; Harrison, Julie A.; Wood, Erica

    2014-01-01

    Purpose This preliminary study compared clinical evaluations for guardianship in three states with varying levels of statutory reform. Design and Methods Case files for 298 cases of adult guardianship were reviewed in Massachusetts, Pennsylvania, and Colorado, three states with varying degrees of statutory reform. The quality and content of the written clinical evidence for guardianship and the hearing outcome were recorded. Results The quality of the written clinical evidence for guardianship was best in Colorado, the state with the most progressive statutory reform, earning a grade of B in our ratings, and worst in Massachusetts, a state with minimal reform, earning a grade of D – with nearly two thirds of the written evidence illegible. Information on specific functional deficits was frequently missing and conclusory statements were common. Information about the individual’s key values and preferences was almost never provided, and individuals were rarely present at the hearing. Limited orders were used for 34% of the cases in Colorado, associated with more complete clinical testimony, but such orders were used in only 1 case in either Massachusetts or Pennsylvania. Implications In this study, states with progressive statutes that promote functional assessment are associated with increased quality of clinical testimony and use of limited orders. A continuing dialogue between clinical and legal professionals is needed to advance reform in guardianship, and thereby provide for the needs and protect the rights of adults who face guardianship proceedings. PMID:17989402

  2. Developing evidence-based dentistry skills: how to interpret randomized clinical trials and systematic reviews.

    PubMed

    Kiriakou, Juliana; Pandis, Nikolaos; Madianos, Phoebus; Polychronopoulou, Argy

    2014-10-30

    Decision-making based on reliable evidence is more likely to lead to effective and efficient treatments. Evidence-based dentistry was developed, similarly to evidence-based medicine, to help clinicians apply current and valid research findings into their own clinical practice. Interpreting and appraising the literature is fundamental and involves the development of evidence-based dentistry (EBD) skills. Systematic reviews (SRs) of randomized controlled trials (RCTs) are considered to be evidence of the highest level in evaluating the effectiveness of interventions. Furthermore, the assessment of the report of a RCT, as well as a SR, can lead to an estimation of how the study was designed and conducted.

  3. The gut microbiota and the liver: implications for clinical practice.

    PubMed

    Quigley, Eamonn M; Monsour, Howard P

    2013-11-01

    While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.

  4. Exploring the relationship between client perspectives, clinical expertise and research evidence.

    PubMed

    Roulstone, Sue

    2015-06-01

    This paper examines the relationship between components of evidence-based practice (clinical expertise, patient perspective and research evidence). Findings are examined from two research programs: the Better Communication Research Program and Child Talk, including exploratory studies of the views of parents and children regarding speech-language pathology and studies of current practice by SLPs in England. Systematic reviews of the research literature were also undertaken. The paper analyses relationships between outcomes valued by children and parents and those reported in the literature and in practice, parents' perspectives regarding intervention in comparison with clinicians' reports of practice and the extent to which research evidence underpins current practice is examined. Parents and children value functional outcomes and positive experiences; these are not routinely measured in research or practice. Therapy is perceived positively by most parents; however, some are ambivalent and less clear about the rationale. Commonly used interventions are supported by evidence, but there are gaps regarding some critical therapy components. The paper discusses four challenges to evidence-based practice: the consistency and clarity of descriptions of interventions; consensus based models of practice; understanding of the mechanisms of change; and, finally, the operationalization of client preferences within an evidence-based practice framework.

  5. Late whiplash syndrome: a clinical science approach to evidence-based diagnosis and management.

    PubMed

    Poorbaugh, Keith; Brismée, Jean-Michel; Phelps, Valerie; Sizer, Phillip S

    2008-01-01

    The purpose of this article is to narrow the gap that exists in the clinical application of scientific research and empiric evidence for the evaluation and management of late whiplash. Considering that 14% to 42% of patients are left with chronic symptoms following whiplash injury, it is unlikely that only minor self-limiting injuries result from the typical rear-end impact. As psychosocial issues play a role in the development of persistent whiplash symptoms, discerning the organic conditions from the biopsychosocial factors remains a challenge to clinicians. The term "whiplash" represents the multiple factors associated with the event, injury, and clinical syndrome that are the end-result of a sudden acceleration-deceleration trauma to the head and neck. However, contentions surround the nature of soft-tissue injuries that occur with most motor vehicle accidents and whether these injuries are significant enough to result in chronic pain and limitations. The stark contrast in litigation for whiplash that exists among industrialized nations and less developed countries suggests another factor that could influence one's interpretation of symptoms' chronicity associated with Late Whiplash Syndrome. There are no gold standard tests or imaging techniques that can objectify whiplash-associated disorders. A lack of supporting evidence and disparity in medico-legal issues have created distinct camps in the scientific interpretations and clinical management of late whiplash. It is likely that efforts in research and/or clinical practice will begin to explain the disparity between acute and chronic whiplash syndrome. Recent evidence suggests that Late Whiplash Syndrome should be considered from a different context. The purpose of this article is to expound on several of the significant findings in the literature and offer clinical applications for evaluation and management of Late Whiplash Syndrome.

  6. Exploring Nurse Manager Support of Evidence-Based Practice: Clinical Nurse Perceptions.

    PubMed

    Caramanica, Laura; Spiva, LeeAnna

    2018-05-01

    The study identifies what constitutes nurse manager (NM) support and other resources that enable clinical nurses (CNs) to engage in evidence-based practice (EBP). Clinical nurses report that NM support enables them to use EBP but what constitutes NM support is still unclear. Nurse managers, CNs, and EBP mentors received specialized education and use a team approach for EBP. Data were collected preintervention, mid-intervention, and postintervention from observations, interviews, journaling, and surveys. Results demonstrate how NMs can perform their role responsibilities and still engage CNs to develop a spirit of inquiry, seek answers to their clinical questions using EBP, and advance their clinical performance to improve patient outcomes. Four NM supportive behaviors emerged: cultivating a shared EBP vision, ensuring use of EBP, communicating the value of EBP, and providing resources for EBP. Through education and support, NMs describe supportive behaviors necessary for the successful conduction of EBP by CNs.

  7. Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

    PubMed

    Creticos, Peter Socrates; Pfaar, Oliver

    2018-06-01

    Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.

  8. Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence.

    PubMed

    Akison, Lisa K; Nitert, Marloes Dekker; Clifton, Vicki L; Moritz, Karen M; Simmons, David G

    2017-06-01

    Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  9. [Evidence and Evidence Gaps - an Introduction].

    PubMed

    Dreier, G; Löhler, J

    2016-04-01

    Treating patients requires the inclusion of existing evidence in any health care decision, to be able to choose the best diagnosis or treatment measure or to make valid prognosis statements for a particular patient in consideration of the physician's own expertise.The basis are clinical trials, the results of which are ideally gathered in systematic reviews, rated, summarized and published. In addition to the GCP (Good Clinical Practice)-compliant planning, conducting and analysis of clinical studies it is essential, that all study results are made publicly available, in order to avoid publication bias. This includes the public registration of planned and discontinued trials. In the last 25 years, the evidence-based medicine (EbM) has increasingly found its way into clinical practice and research. Here EbM is closely associated with the names Archibald Cochrane and David Sackett. In Germany, both the German Cochrane Centre (DCZ) and the network of evidence-based medicine (DNEbM) were established approximately 15 years ago. In the international Cochrane Collaboration clinicians and other scientists like statisticians interdisciplinary work side by side to develop the methods of evidence-based medicine and to address the topics of evidence generation and processing as well as the transfer of knowledge. Challenge: Existing evidence primarily serves doctors to support their decision-making, but is also the basis for providing scientific proof for a health care intervention's benefit to patients and ultimately payers/health insurances. The closure of existing evidence gaps requires substantial human and financial resources, a complex organizational structure and can only succeed with the involvement of clinical and methodological expertise and specific knowledge in the field of clinical research. In addition, the knowledge must be transferred into practice, using journals, guidelines, conferences, databases, information portals with processed evidence and not least the

  10. Clinical studies of innovative medical devices: what level of evidence for hospital-based health technology assessment?

    PubMed

    Boudard, Aurélie; Martelli, Nicolas; Prognon, Patrice; Pineau, Judith

    2013-08-01

    Like health technology assessment (HTA) agencies, hospitals are faced with requests for innovative and costly medical devices. However, local decision makers are frequently confronted with a lack of high-quality clinical data when assessing the effectiveness of innovative medical devices. The aim of this study was to quantify the level of evidence available for innovative medical devices in the context of hospital-based HTA. We searched the Medline, Embase and Cochrane Library databases for articles, letters and reports relating to 32 innovative medical devices requested at our hospital between January 2008 and March 2012. All clinical studies retrieved were screened and classified according to the Sackett 5-point level-of-evidence scale. We screened and classified 217 studies: 215 clinical trials and 2 cost-effectiveness studies. Only 47 of the 215 clinical studies (22%) provided high-level clinical evidence (levels 1-2); 33 (15%) were randomized controlled trials (RCTs). More than half of the 215 studies (52.1%) included fewer than 30 patients. Only 14 of the 47 high-quality studies reported the amount of missing data. For implantable medical devices, 84 (71.8%) studies specified the follow-up period and the mean follow-up period was 18.9 months. Finally, methodological quality did not increase with the risk level of the medical device. Our findings confirm that only a few studies of innovative medical devices provide high-level clinical evidence. Nevertheless, RCT may be the 'gold standard' for drugs, but it is not always appropriate for medical devices. Changes to the European regulation of medical devices, with the requirement for a demonstration of clinical efficacy and safety before release onto the European market, have raised expectations. © 2013 John Wiley & Sons Ltd.

  11. Evidence of the economic benefit of clinical pharmacy services: 1996-2000.

    PubMed

    Schumock, Glen T; Butler, Melissa G; Meek, Patrick D; Vermeulen, Lee C; Arondekar, Bhakti V; Bauman, Jerry L

    2003-01-01

    We sought to summarize and assess original evaluations of the economic impact of clinical pharmacy services published from 1996-2000, and to provide recommendations and methodologic considerations for future research. A systematic literature search was conducted to identify articles that were then blinded and randomly assigned to reviewers who confirmed inclusion and abstracted key information. Results were compared with those of a similar review of literature published from 1988-1995. In the 59 included articles, the studies were conducted across a variety of practice sites that consisted of hospitals (52%), community pharmacies and clinics (41%), health maintenance organizations (3%), and long-term or intermediate care facilities (3%). They focused on a broad range of clinical pharmacy services such as general pharmacotherapeutic monitoring (47%), target drug programs (20%), disease management programs (10%), and patient education or cognitive services (10%). Compared with the studies of the previous review, a greater proportion of evaluations were conducted in community pharmacies or clinics, and the types of services evaluated tended to be more comprehensive rather than specialized. Articles were categorized by type of evaluation: 36% were considered outcome analyses, 24% full economic analyses, 17% outcome descriptions, 15% cost and outcome descriptions, and 8% cost analyses. Compared with the studies of the previous review, a greater proportion of studies in the current review used more rigorous study designs. Most studies reported positive financial benefits of the clinical pharmacy service evaluated. In 16 studies, a benefit:cost ratio was reported by the authors or was able to be calculated by the reviewers (these ranged from 1.7:1-17.0:1, median 4.68:1). The body of literature from this 5-year period provides continued evidence of the economic benefit of clinical pharmacy services. Although the quality of study design has improved, whenever possible

  12. Mechanisms of intrahepatic triglyceride accumulation

    PubMed Central

    Ress, Claudia; Kaser, Susanne

    2016-01-01

    Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD. PMID:26819531

  13. Delay of gratification by orangutans (Pongo pygmaeus) in the accumulation task.

    PubMed

    Parrish, Audrey E; Perdue, Bonnie M; Stromberg, Erin E; Bania, Amanda E; Evans, Theodore A; Beran, Michael J

    2014-05-01

    There is considerable evidence indicating that chimpanzees can delay gratification for extended time intervals, particularly in the accumulation task in which food items accumulate within a participant's reach until the participant begins to consume them. However, there is limited evidence that other ape species might also exhibit this capacity, despite there being a number of similar studies indicating that nonape species (e.g., monkeys and birds) can delay gratification, but not for nearly as long as chimpanzees. To help define the taxonomic distribution of delay of gratification behavior in the order Primates, we tested 6 orangutans in the current experiments and compared their performance with comparable data from a previous study with capuchin monkeys. We varied delay length and visibility of the items that were still available for accumulation to determine the impact of these factors on performance. Species differences on the accumulation task emerged when comparing the current data to data from a previous study. Orangutans outperformed capuchin monkeys, suggesting that ape species may generally show better delay of gratification and delay maintenance abilities than monkeys. However, more studies are necessary to rule out alternative hypotheses on the distribution of delay maintenance abilities across primate species. ©2014 APA, all rights reserved.

  14. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

    PubMed Central

    Kotecha, Ritesh; Takami, Akiyoshi; Espinoza, J. Luis

    2016-01-01

    Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations. PMID:27232756

  15. Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

    PubMed Central

    Chen, Jiao; Li, Xiaozhong; Bai, Zhenjiang; Fang, Fang; Hua, Jun; Li, Ying; Pan, Jian; Wang, Jian; Feng, Xing; Li, Yanhong

    2016-01-01

    Objective To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis. Methods This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission. Results Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08–1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15–25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ≥10%: 4 [3–8], 7 [4–11] vs. 10 [6–16] days; P <0.001; n = 154) and in survivors (4 [3–8], 7 [5–11] vs. 10 [5–15] days; P <0.001; n = 121). Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65–0.82; P <0.001; n = 202) for predicting mortality in patients with severe sepsis, with a sensitivity of 67

  16. Urinary urgency - translating the evidence base into daily clinical practice.

    PubMed

    Cardozo, L; Chapple, C R; Dmochowski, R; Fitzgerald, M P; Hanno, P; Michel, M C; Staskin, D; Van Kerrebroeck, P; Wyndaele, J-J; Yamaguchi, O; Yoshida, M

    2009-12-01

    To consider the currently available knowledge and understanding of the symptom of urgency. Each faculty member reviewed the literature base of a different aspect of urgency and along with their personal clinical experience provided a base of evidence for discussion. This overview summarises relevant published literature and the current clinical experience of the authors. Whilst the mechanisms producing the sensation of urgency are still not fully understood and we are working within a definition that may complicate measurement and treatment, our pressing need is to effectively manage our patients for whom the practical nature of urgency can be all too apparent. Health care professionals have an important role to play today in helping to alleviate the widespread problem of urgency and its consequences.

  17. Thinking and practice of accelerating transformation of traditional Chinese medicine from experience medicine to evidence-based medicine.

    PubMed

    Liu, Baoyan; Zhang, Yanhong; Hu, Jingqing; He, Liyun; Zhou, Xuezhong

    2011-06-01

    The gradual development of Chinese medicine is based on constant accumulation and summary of experience in clinical practice, but without the benefit of undergoing the experimental medicine stage. Although Chinese medicine has formed a systematic and unique theory system through thousands of years, with the development of evidence-based medicine, the bondage of the research methods of experience medicine to Chinese medicine is appearing. The rapid transition and transformation from experience medicine to evidence-based medicine have become important content in the development of Chinese medicine. According to the features of Chinese medicine, we propose the research idea of "taking two ways simultaneously," which is the study both in the ideal condition and in the real world. Analyzing and constructing the theoretical basis and methodology of clinical research in the real world, and building the stage for research technique is key to the effective clinical research of Chinese medicine. Only by gradually maturing and completing the clinical research methods of the real world could we realize "taking two ways simultaneously" and complementing each other, continuously produce scientific and reliable evidence of Chinese medicine, as well as transform and develop Chinese medicine from experience medicine to evidence-based medicine.

  18. Transforming clinical practice guidelines and clinical pathways into fast-and-frugal decision trees to improve clinical care strategies.

    PubMed

    Djulbegovic, Benjamin; Hozo, Iztok; Dale, William

    2018-02-27

    Contemporary delivery of health care is inappropriate in many ways, largely due to suboptimal Q5 decision-making. A typical approach to improve practitioners' decision-making is to develop evidence-based clinical practice guidelines (CPG) by guidelines panels, who are instructed to use their judgments to derive practice recommendations. However, mechanisms for the formulation of guideline judgments remains a "black-box" operation-a process with defined inputs and outputs but without sufficient knowledge of its internal workings. Increased explicitness and transparency in the process can be achieved by implementing CPG as clinical pathways (CPs) (also known as clinical algorithms or flow-charts). However, clinical recommendations thus derived are typically ad hoc and developed by experts in a theory-free environment. As any recommendation can be right (true positive or negative), or wrong (false positive or negative), the lack of theoretical structure precludes the quantitative assessment of the management strategies recommended by CPGs/CPs. To realize the full potential of CPGs/CPs, they need to be placed on more solid theoretical grounds. We believe this potential can be best realized by converting CPGs/CPs within the heuristic theory of decision-making, often implemented as fast-and-frugal (FFT) decision trees. This is possible because FFT heuristic strategy of decision-making can be linked to signal detection theory, evidence accumulation theory, and a threshold model of decision-making, which, in turn, allows quantitative analysis of the accuracy of clinical management strategies. Fast-and-frugal provides a simple and transparent, yet solid and robust, methodological framework connecting decision science to clinical care, a sorely needed missing link between CPGs/CPs and patient outcomes. We therefore advocate that all guidelines panels express their recommendations as CPs, which in turn should be converted into FFTs to guide clinical care. © 2018 John Wiley

  19. The role of external evidence in data monitoring of a clinical trial.

    PubMed

    Pocock, S J

    1996-06-30

    Data monitoring of interim results from a randomized clinical trial should take into consideration evidence from other trials. This article presents both scientific and practical issues regarding the pros and cons of formally incorporating such external evidence into the decision making process for the current trial. Guidelines on how to use other trials' data are presented, along with cautiously sceptical comments on the impracticality of using formal meta-analyses in data monitoring. The arguments are illustrated by recent examples from specific trials, and the article concludes with some general recommendations.

  20. Developing clinical strength-of-evidence approach to define HIV-associated malignancies for cancer registration in Kenya.

    PubMed

    Korir, Anne; Mauti, Nathan; Moats, Pamela; Gurka, Matthew J; Mutuma, Geoffrey; Metheny, Christine; Mwamba, Peter M; Oyiro, Peter O; Fisher, Melanie; Ayers, Leona W; Rochford, Rosemary; Mwanda, Walter O; Remick, Scot C

    2014-01-01

    Sub-Saharan Africa cancer registries are beset by an increasing cancer burden further exacerbated by the AIDS epidemic where there are limited capabilities for cancer-AIDS match co-registration. We undertook a pilot study based on a "strength-of-evidence" approach using clinical data that is abstracted at the time of cancer registration for purposes of linking cancer diagnosis to AIDS diagnosis. The standard Nairobi Cancer Registry form was modified for registrars to abstract the following clinical data from medical records regarding HIV infection/AIDS in a hierarchal approach at time of cancer registration from highest-to-lowest strength-of-evidence: 1) documentation of positive HIV serology; 2) antiretroviral drug prescription; 3) CD4+ lymphocyte count; and 4) WHO HIV clinical stage or immune suppression syndrome (ISS), which is Kenyan terminology for AIDS. Between August 1 and October 31, 2011 a total of 1,200 cancer cases were registered. Of these, 171 cases (14.3%) met clinical strength-of-evidence criteria for association with HIV infection/AIDS; 69% (118 cases were tumor types with known HIV association - Kaposi's sarcoma, cervical cancer, non-Hodgkin's and Hodgkin's lymphoma, and conjunctiva carcinoma) and 31% (53) were consistent with non-AIDS defining cancers. Verifiable positive HIV serology was identified in 47 (27%) cases for an absolute seroprevalence rate of 4% among the cancer registered cases with an upper boundary of 14% among those meeting at least one of strength-of-evidence criteria. This pilot demonstration of a hierarchal, clinical strength-of-evidence approach for cancer-AIDS registration in Kenya establishes feasibility, is readily adaptable, pragmatic, and does not require additional resources for critically under staffed cancer registries. Cancer is an emerging public health challenge, and African nations need to develop well designed population-based studies in order to better define the impact and spectrum of malignant disease in the

  1. Boric acid for recurrent vulvovaginal candidiasis: the clinical evidence.

    PubMed

    Iavazzo, Christos; Gkegkes, Ioannis D; Zarkada, Ioanna M; Falagas, Matthew E

    2011-08-01

    Recurrent vulvovaginal candidiasis (VVC) remains a challenge to manage in clinical practice. Recent epidemiologic studies indicate that non-albicans Candida spp. are more resistant to conventional antifungal treatment with azoles and are considered as causative pathogens of vulvovaginal candidiasis. We searched PubMed and Scopus for studies that reported clinical evidence on the intravaginal use of boric acid for vulvovaginal candidiasis. We identified 14 studies (2 randomized clinical trials [RCTs], 9 case series, and 4 case reports) as eligible for inclusion in this review. Boric acid was compared with nystatin, terconazole, flucytosine, itraconazole, clotrimazole, ketoconazole, fluconazole, buconazole, and miconazole; as monotherapy, boric acid was studied in 7 studies. The mycologic cure rates varied from 40% to 100% in patients treated with boric acid; 4 of the 9 included case series reported statistically significant outcomes regarding cure (both mycologic and clinical) rates. None of the included studies reported statistically significant differences in recurrence rates. Regarding the adverse effects caused by boric acid use, vaginal burning sensation (<10% of cases), water discharge during treatment, and vaginal erythema were identified in 7 studies. Our findings suggest that boric acid is a safe, alternative, economic option for women with recurrent and chronic symptoms of vaginitis when conventional treatment fails because of the involvement of non-albicans Candida spp. or azole-resistant strains.

  2. Improving the clinical evidence of bone graft substitute technology in lumbar spine surgery.

    PubMed

    Hsu, Wellington K; Nickoli, M S; Wang, J C; Lieberman, J R; An, H S; Yoon, S T; Youssef, J A; Brodke, D S; McCullough, C M

    2012-12-01

    Bone graft substitutes have been used routinely for spine fusion for decades, yet clinical evidence establishing comparative data remains sparse. With recent scrutiny paid to the outcomes, complications, and costs associated with osteobiologics, a need to improve available data guiding efficacious use exists. We review the currently available clinical literature, studying the outcomes of various biologics in posterolateral lumbar spine fusion, and establish the need for a multicenter, independent osteobiologics registry.

  3. Cannabinoid-based medicines for neurological disorders--clinical evidence.

    PubMed

    Wright, Stephen

    2007-08-01

    Whereas the cannabis plant has a long history of medicinal use, it is only in recent years that a sufficient understanding of the pharmacology of the main plant constituents has allowed for a better understanding of the most rational therapeutic targets. The distribution of cannabinoid receptors, both within the nervous system and without, and the development of pharmacological tools to investigate their function has lead to a substantial increase in efforts to develop cannabinoids as therapeutic agents. Concomitant with these efforts, the understanding of the pharmacology of plant cannabinoids at receptor and other systems distinct from the cannabinoid receptors suggests that the therapeutic applications of plant-derived cannabinoids (and presumably their synthetic derivatives also) may be diverse. This review aims to discuss the clinical evidence investigating the use of medicines derived, directly or indirectly, from plant cannabinoids with special reference to neurological disorders. Published studies suggest that the oral administration of cannabinoids may not be the preferred route of administration and that plant extracts show greater evidence of efficacy than synthetic compounds. One of these, Sativex (GW Pharmaceuticals), was approved as a prescription medicine in Canada in 2005 and is currently under regulatory review in the EU.

  4. Tendinopathy: Evidence-Informed Physical Therapy Clinical Reasoning.

    PubMed

    Vicenzino, Bill

    2015-11-01

    Patients presenting with pain at the tendon, which is associated with physical tasks and activities that specifically load that tendon, are at the center of this special issue. The current terminology for a symptomatic tendon presentation is tendinopathy, as this does not denote an underlying pathology, but rather signals that all is not well in the tendon. Tendinopathy is a prevalent and substantial problem, as it interferes with a person's capacity to lead a physically active and healthy life, which has a considerable flow-on effect on society in general. This issue deals with the contemporary physical therapy management of tendinopathy by providing a mix of evidence review and clinical expert opinion on commonly presenting tendinopathies of the lower and upper limbs. J Orthop Sports Phys Ther 2015;45(11):816-818. doi:10.2519/jospt.2015.0110.

  5. Evidence review and clinical guidance for the use of ziprasidone in Canada

    PubMed Central

    2013-01-01

    While indicated for schizophrenia and acute mania, ziprasidone’s evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success PMID:23347694

  6. [Evidence-based clinical oral healthcare guidelines 4. Adherence requires an implementation strategy].

    PubMed

    Braspenning, J C C; Mettes, T G P H; van der Sanden, W J M; Wensing, M J P

    2015-03-01

    Adherence to clinical guidelines requires support in practice. However, systematic implementation of evidence-based guidelines is not common practice in oral healthcare. The Knowledge Institute Oral Care (KiMo) offers the opportunity to take into account potential barriers and facilitators during the development of evidence-based clinical practice guidelines. These factors which are relevant to the guideline and the oral healthcare practice provide the ingredients for a tailor-made programme of implementation that has a scientific basis. Elements of any implementation programme are the quality indicators derived from the oral healthcare guidelines. These indicators should fit, on the one hand, the specific goals of the guidelines (patient safety, effectiveness, efficiency, patient-centred, timeliness, accessibility) and, onthe other hand, the various perspectives of the different stakeholders, such as patients, caregivers, health insurers and inspectorate. These quality indicators provide information on adherence to the guidelines, the results of a certain treatment and the success of the implementation strategy, all with the aim to improve the quality of oral healthcare.

  7. Contemporary evidence-based practice in Canadian emergency medical services: a vision for integrating evidence into clinical and policy decision-making.

    PubMed

    Jensen, Jan L; Travers, Andrew H

    2017-05-01

    Nationally, emphasis on the importance of evidence-based practice (EBP) in emergency medicine and emergency medical services (EMS) has continuously increased. However, meaningful incorporation of effective and sustainable EBP into clinical and administrative decision-making remains a challenge. We propose a vision for EBP in EMS: Canadian EMS clinicians and leaders will understand and use the best available evidence for clinical and administrative decision-making, to improve patient health outcomes, the capability and quality of EMS systems of care, and safety of patients and EMS professionals. This vision can be implemented with the use of a structure, process, system, and outcome taxonomy to identify current barriers to true EBP, to recognize the opportunities that exist, and propose corresponding recommended strategies for local EMS agencies and at the national level. Framing local and national discussions with this approach will be useful for developing a cohesive and collaborative Canadian EBP strategy.

  8. [Job crisis and transformations in the new model of accumulation].

    PubMed

    Zerda-Sarmiento, Alvaro

    2012-06-01

    The general and structural crisis capitalism is going through is the token of the difficulties accumulation model has been dealing with since 70's in developed countries. This model has been trying to settle down again on the basis of neoliberal principle and a new technical-economical paradigm. The new accumulation pattern has had a effect in employment sphere which have been made evident at all the elements that constitute work relationships. In Colombia, this model implementation has been partial and segmented. However, its consequences (and the long-term current crisis) have been evident in unemployment, precarious work, segmentation, informal work and restricted and private health insurance. Besides, financial accumulation makes labour profits flow at different levels. The economic model current government has aimed to implement leads to strengthening exports, so making population life conditions more difficult. In order to overcome the current state of affairs, the work sphere needs to become more creative. This creative approach should look for new schemes for expression and mobilization of work sphere's claims. This is supposed to be done by establishing a different economic model aimed to build a more inclusive future, with social justice.

  9. Using the core curriculum on childhood trauma to strengthen clinical knowledge in evidence-based practitioners.

    PubMed

    Layne, Christopher M; Strand, Virginia; Popescu, Marciana; Kaplow, Julie B; Abramovitz, Robert; Stuber, Margaret; Amaya-Jackson, Lisa; Ross, Leslie; Pynoos, Robert S

    2014-01-01

    The high prevalence of trauma exposure in mental health service-seeking populations, combined with advances in evidence-based practice, competency-based training, common-elements research, and adult learning make this an opportune time to train the mental health workforce in trauma competencies. The Core Curriculum on Childhood Trauma (CCCT) utilizes a five-tiered conceptual framework (comprising Empirical Evidence, Core Trauma Concepts, Intervention Objectives, Practice Elements, and Skills), coupled with problem-based learning, to build foundational trauma knowledge and clinical reasoning skills. We present findings from three studies: Study 1 found that social work graduate students' participation in a CCCT course (N = 1,031) was linked to significant pre-post increases in self-reported confidence in applying core trauma concepts to their clinical work. Study 2 found significant pre-post increases in self-reported conceptual readiness (N = 576) and field readiness (N = 303) among social work graduate students participating in a "Gold Standard Plus" educational model that integrated classroom instruction in core trauma concepts, training in evidence-based trauma treatment (EBTT), and implementation of that EBTT in a supervised field placement. Students ranked the core concepts course as an equivalent or greater contributor to field readiness compared to standard EBTT training. Study 3 used qualitative methods to "distill" common elements (35 intervention objectives, 59 practice elements) from 26 manualized trauma interventions. The CCCT is a promising tool for educating "next-generation" evidence-based practitioners who possess competencies needed to implement modularized, individually tailored trauma interventions by strengthening clinical knowledge, clinical reasoning, and familiarity with common elements.

  10. Accumulator and random-walk models of psychophysical discrimination: a counter-evaluation.

    PubMed

    Vickers, D; Smith, P

    1985-01-01

    In a recent assessment of models of psychophysical discrimination, Heath criticises the accumulator model for its reliance on computer simulation and qualitative evidence, and contrasts it unfavourably with a modified random-walk model, which yields exact predictions, is susceptible to critical test, and is provided with simple parameter-estimation techniques. A counter-evaluation is presented, in which the approximations employed in the modified random-walk analysis are demonstrated to be seriously inaccurate, the resulting parameter estimates to be artefactually determined, and the proposed test not critical. It is pointed out that Heath's specific application of the model is not legitimate, his data treatment inappropriate, and his hypothesis concerning confidence inconsistent with experimental results. Evidence from adaptive performance changes is presented which shows that the necessary assumptions for quantitative analysis in terms of the modified random-walk model are not satisfied, and that the model can be reconciled with data at the qualitative level only by making it virtually indistinguishable from an accumulator process. A procedure for deriving exact predictions for an accumulator process is outlined.

  11. A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

    PubMed

    Rath, Ana; Salamon, Valérie; Peixoto, Sandra; Hivert, Virginie; Laville, Martine; Segrestin, Berenice; Neugebauer, Edmund A M; Eikermann, Michaela; Bertele, Vittorio; Garattini, Silvio; Wetterslev, Jørn; Banzi, Rita; Jakobsen, Janus C; Djurisic, Snezana; Kubiak, Christine; Demotes-Mainard, Jacques; Gluud, Christian

    2017-11-22

    Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement. Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Barriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes. Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases.

  12. Dietary fats and F2-isoprostanes: A review of the clinical evidence.

    PubMed

    Da Silva, Marine S; Bilodeau, Jean-François; Julien, Pierre; Rudkowska, Iwona

    2017-12-12

    Evidence supports that a high dietary fat intake increases oxidative stress and the risk of diet-induced metabolic disorders such as obesity, diabetes and cardiovascular diseases. F 2 -isoprostanes (F 2 -isoP) are formed by the non-enzymatic oxidation of arachidonic acid and are widely used as reliable biomarkers of oxidative stress in clinical studies. Dietary fats may influence F 2 -isoP levels, as they (1) are metabolic substrates for their formation, (2) modify the lipid composition of tissues, and (3) affect the plasma lipoprotein concentrations which are involved in F 2 -isoP transport. This review examined the latest clinical evidence on how dietary fats can affect blood circulation and excretion of F 2 -isoP in individuals with healthy or deteriorated metabolic profiles. Clinical studies reported that saturated or monounsaturated fat-rich diets did not affect F 2 -isoP levels in adults with healthy or deteriorated metabolic profiles. Though, ω-3 polyunsaturated fatty acids decreased F 2 -isoP levels in numerous studies, whereas trans-fatty acids raised F 2 -isoP excretion. Yet, the reported heterogeneous results reveal important considerations, such as the health status of the participants, the biological fluids used to determine F 2 -isoP, the analytical methods employed and the specific F 2 -isoP isomers detected. Therefore, future clinical studies should be designed in order to consider these issues in the studies of the effects of fat intake on oxidative stress.

  13. Concordance Between Clinical Practice and Published Evidence: Findings From Virginia Commonwealth University School of Dentistry.

    PubMed

    Chiang, Harmeet K; Best, Al M; Sarrett, David C

    2017-09-01

    To evaluate the concordance between clinical practice and published evidence by dental faculty and graduating students of the Virginia Commonwealth University School of Dentistry. A questionnaire previously developed by the National Dental Practice-Based Research Network with 12 clinical scenarios was administered to VCU faculty and graduating students. Responses were scored as either consistent or inconsistent with published evidence and then analyzed for differences between dental faculty, graduating students, and the national results. There were 43 dental faculty members with at least half-time student contact who responded to the survey. Faculty concordance ranged from 33% to 100%, and general practice faculty had the highest concordance (82%). Eighty-five of the graduating class of 98 responded to the survey, and student concordance ranged from 18% to 92% and averaged 67%. General practice faculty had higher concordance with published evidence than recently graduated dental students. Graduating students and dental faculty demonstrated higher concordance with evidence-based practice than practitioners in the National Dental Practice-Based Research Network. General practice dental faculty demonstrated adequate concordance, but students demonstrated only a medium-level concordance. Practitioners involved in teaching dental students are better able to keep up with evolving evidence and are better able to demonstrate evidence-based practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Scientific evidence of dockworker illness to nursing clinical reasoning.

    PubMed

    Almeida, Marlise Capa Verde de; Cezar-Vaz, Marta Regina

    2016-04-01

    To identify scientific evidence of occupational illness of dockworkers published in the literature. systematic review of the literature, developed according to the Cochrane method. The databases searched were: Cochrane, LILACS, MEDLINE/PubMed, CINAHL and SciELO. Studies from 1988 to 2014 were selected. The data were analyzed according to the level of evidence and Strengthening the Reporting of Observational Studies in Epidemiology. We included 14 studies, in which 11 (78.6%) were from international journals. The year of 2012 showed greater number of studies. All studies were classified as: Level of Evidence 4, highlighting lung cancer, musculoskeletal and ischemic diseases, causal link in chemical risks. The development of preventive measures should especially include chemical exposure of workers applying the clinical reasoning of nurses' environmental knowledge to care for illnesses. Identificar evidências científicas de adoecimento ocupacional do trabalhador portuário publicadas na literatura. Revisão sistemática da literatura, construída conforme o método Cochrane. As bases de dados pesquisadas foram Cochrane, LILACS, MEDLINE/PubMed, CINAHL e SciELO. Foram selecionados artigos publicados de 1988 a 2014. Os dados foram analisados conforme o Nível de Evidência e Strengthening the Reporting of Observational Studies in Epidemiology. Foram selecionadas 14 publicações, das quais 11 (78,6%) de revistas internacionais. O ano de 2012 reuniu maior número de publicações no período de estudo. Todas as publicações pertenciam ao Nível de Evidência 4, destacando o câncer pulmonar, doenças osteomusculares e isquêmicas, com nexo causal nos riscos químicos. A elaboração de medidas preventivas deve prever especialmente a exposição química do trabalhador, aplicando ao raciocínio clínico do enfermeiro um conhecimento ambiental para a assistência aos adoecimentos.

  15. Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment.

    PubMed

    Bayer, T A; Wirths, O

    2008-02-01

    Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.

  16. Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation

    PubMed Central

    Li, Ying; Chang, Wenqiang; Zhang, Ming; Li, Xiaobin; Jiao, Yang; Lou, Hongxiang

    2015-01-01

    Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD), a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS), which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections. PMID:26047493

  17. Improving the Clinical Evidence of Bone Graft Substitute Technology in Lumbar Spine Surgery

    PubMed Central

    Hsu, Wellington K.; Nickoli, M. S.; Wang, J. C.; Lieberman, J. R.; An, H. S.; Yoon, S. T.; Youssef, J. A.; Brodke, D. S.; McCullough, C. M.

    2012-01-01

    Bone graft substitutes have been used routinely for spine fusion for decades, yet clinical evidence establishing comparative data remains sparse. With recent scrutiny paid to the outcomes, complications, and costs associated with osteobiologics, a need to improve available data guiding efficacious use exists. We review the currently available clinical literature, studying the outcomes of various biologics in posterolateral lumbar spine fusion, and establish the need for a multicenter, independent osteobiologics registry. PMID:24353975

  18. A pragmatic evidence-based clinical management algorithm for burning mouth syndrome.

    PubMed

    Kim, Yohanan; Yoo, Timothy; Han, Peter; Liu, Yuan; Inman, Jared C

    2018-04-01

    Burning mouth syndrome is a poorly understood disease process with no current standard of treatment. The goal of this article is to provide an evidence-based, practical, clinical algorithm as a guideline for the treatment of burning mouth syndrome. Using available evidence and clinical experience, a multi-step management algorithm was developed. A retrospective cohort study was then performed, following STROBE statement guidelines, comparing outcomes of patients who were managed using the algorithm and those who were managed without. Forty-seven patients were included in the study, with 21 (45%) managed using the algorithm and 26 (55%) managed without. The mean age overall was 60.4 ±16.5 years, and most patients (39, 83%) were female. Cohorts showed no statistical difference in age, sex, overall follow-up time, dysgeusia, geographic tongue, or psychiatric disorder; xerostomia, however, was significantly different, skewed toward the algorithm group. Significantly more non-algorithm patients did not continue care (69% vs. 29%, p =0.001). The odds ratio of not continuing care for the non-algorithm group compared to the algorithm group was 5.6 [1.6, 19.8]. Improvement in pain was significantly more likely in the algorithm group ( p =0.001), with an odds ratio of 27.5 [3.1, 242.0]. We present a basic clinical management algorithm for burning mouth syndrome which may increase the likelihood of pain improvement and patient follow-up. Key words: Burning mouth syndrome, burning tongue, glossodynia, oral pain, oral burning, therapy, treatment.

  19. Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

    PubMed

    Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

    2013-01-01

    Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

  20. Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

    PubMed Central

    Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

    2016-01-01

    An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

  1. Five-year review of an international clinical research-training program

    PubMed Central

    Suemoto, Claudia Kimie; Ismail, Sherine; Corrêa, Paulo César Rodrigues Pinto; Khawaja, Faiza; Jerves, Teodoro; Pesantez, Laura; Germani, Ana Claudia Camargo Gonçalves; Zaina, Fabio; dos Santos, Augusto Cesar Soares; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomás, Rita; Illigens, Ben MW; Fregni, Felipe

    2015-01-01

    The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008–2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background. PMID:25878518

  2. Five-year review of an international clinical research-training program.

    PubMed

    Suemoto, Claudia Kimie; Ismail, Sherine; Corrêa, Paulo César Rodrigues Pinto; Khawaja, Faiza; Jerves, Teodoro; Pesantez, Laura; Germani, Ana Claudia Camargo Gonçalves; Zaina, Fabio; Dos Santos, Augusto Cesar Soares; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomás, Rita; Illigens, Ben Mw; Fregni, Felipe

    2015-01-01

    The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background.

  3. Keeping agricultural soil out of rivers: evidence of sediment and nutrient accumulation within field wetlands in the UK.

    PubMed

    Ockenden, Mary C; Deasy, Clare; Quinton, John N; Surridge, Ben; Stoate, Chris

    2014-03-15

    Intensification of agriculture has resulted in increased soil degradation and erosion, with associated pollution of surface waters. Small field wetlands, constructed along runoff pathways, offer one option for slowing down and storing runoff in order to allow more time for sedimentation and for nutrients to be taken up by plants or micro-organisms. This paper describes research to provide quantitative evidence for the effectiveness of small field wetlands in the UK landscape. Ten wetlands were built on four farms in Cumbria and Leicestershire, UK. Annual surveys of sediment and nutrient accumulation in 2010, 2011 and 2012 indicated that most sediment was trapped at a sandy site (70 tonnes over 3 years), compared to a silty site (40 tonnes over 3 years) and a clay site (2 tonnes over 3 years). The timing of rainfall was more important than total annual rainfall for sediment accumulation, with most sediment transported in a few intense rainfall events, especially when these coincided with bare soil or poor crop cover. Nutrient concentration within sediments was inversely related to median particle size, but the total mass of nutrients trapped was dependent on the total mass of sediment trapped. Ratios of nutrient elements in the wetland sediments were consistent between sites, despite different catchment characteristics across the individual wetlands. The nutrient value of sediment collected from the wetlands was similar to that of soil in the surrounding fields; dredged sediment was considered to have value as soil replacement but not as fertiliser. Overall, small field wetlands can make a valuable contribution to keeping soil out of rivers. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Clinical team functioning and IT innovation: a study of the diffusion of a point-of-care online evidence system.

    PubMed

    Gosling, A Sophie; Westbrook, Johanna I; Braithwaite, Jeffrey

    2003-01-01

    To investigate the association between clinical team functioning and diffusion (awareness, use, and impact) of a 24-hour online evidence retrieval system. To examine the relationships between clinical team characteristics and the adoption of the online evidence system. 18 clinical teams, consisting of 180 clinicians from three Australian hospitals, were identified and studied. Teams were categorized as small ( 15). Clinical team functioning was assessed using the Team Climate Inventory (TCI). Awareness, use, and impact of an online evidence retrieval system were measured using a self-administered questionnaire. The relationships between TCI scores and awareness, use, and impact were examined using t-tests and one-way ANOVAs. Chi square analyses were used to examine differences between small and large teams. RESULTS were interpreted within a diffusion of innovations framework. Clinical team functioning was not related to awareness or use of the online evidence retrieval system. However, clinical team functioning was significantly associated with the impact of online evidence in terms of reported experience of improved patient care following system use. Clinicians in small teams ( 15) teams. Team functioning had the greatest impact on the fourth stage of innovation diffusion, the effective use of online evidence for clinical care. This supports Rogers' diffusion of innovation theory, to the effect that different types of communication about an innovation are important at different stages in the diffusion process. Members of small teams were more aware of the system than members of large teams. Team functioning is amenable to improvement through interventions. The findings suggest that the role of team climate in the diffusion of information systems is a promising area for future research.

  5. Description of a Standardized Treatment Center that Utilizes Evidence-Based Clinic Operations to Facilitate Implementation of an Evidence-Based Treatment

    ERIC Educational Resources Information Center

    Donohue, Brad; Allen, Daniel N.; Romero, Valerie; Hill, Heather H.; Vasaeli, Kathryn; Lapota, Holly; Tracy, Kendra; Gorney, Suzanne; Abdel-al, Ruweida; Caldas, Diana; Herdzik, Karen; Bradshaw, Kelsey; Valdez, Robby; Van Hasselt, Vincent B.

    2009-01-01

    Developers of evidence-based therapies are enhancing methods of teaching therapists to implement "best practices" with integrity. However, there is a relative dearth of information available as to clinic operations and related contextual factors necessary to sustain successful implementation of these treatments. This article describes various…

  6. Regulatory effects of curcumin on lipid accumulation in monocytes/macrophages

    USDA-ARS?s Scientific Manuscript database

    Recent evidence suggests potential benefits from phytochemicals and micronutrients in protecting against oxidative and lipid-mediated damage, but the molecular mechanisms of these actions are still unclear. Here we investigated whether the dietary polyphenol curcumin can modulate the accumulation of...

  7. Tacit knowledge as the unifying factor in evidence based medicine and clinical judgement

    PubMed Central

    Thornton, Tim

    2006-01-01

    The paper outlines the role that tacit knowledge plays in what might seem to be an area of knowledge that can be made fully explicit or codified and which forms a central element of Evidence Based Medicine. Appeal to the role the role of tacit knowledge in science provides a way to unify the tripartite definition of Evidence Based Medicine given by Sackett et al: the integration of best research evidence with clinical expertise and patient values. Each of these three elements, crucially including research evidence, rests on an ineliminable and irreducible notion of uncodified good judgement. The paper focuses on research evidence, drawing first on the work of Kuhn to suggest that tacit knowledge contributes, as a matter of fact, to puzzle solving within what he calls normal science. A stronger argument that it must play a role in research is first motivated by looking to Collins' first hand account of replication in applied physics and then broader considerations of replication in justifying knowledge claims in scientific research. Finally, consideration of an argument from Wittgenstein shows that whatever explicit guidelines can be drawn up to guide judgement the specification of what counts as correctly following them has to remain implicit. Overall, the paper sets out arguments for the claim that even though explicit guidelines and codifications can play a practical role in informing clinical practice, they rest on a body of tacit or implicit skill that is in principle ineliminable. It forms the bedrock of good judgement and unites the integration of research, expertise and values. PMID:16759426

  8. Tacit knowledge as the unifying factor in evidence based medicine and clinical judgement.

    PubMed

    Thornton, Tim

    2006-03-17

    The paper outlines the role that tacit knowledge plays in what might seem to be an area of knowledge that can be made fully explicit or codified and which forms a central element of Evidence Based Medicine. Appeal to the role the role of tacit knowledge in science provides a way to unify the tripartite definition of Evidence Based Medicine given by Sackett et al: the integration of best research evidence with clinical expertise and patient values. Each of these three elements, crucially including research evidence, rests on an ineliminable and irreducible notion of uncodified good judgement. The paper focuses on research evidence, drawing first on the work of Kuhn to suggest that tacit knowledge contributes, as a matter of fact, to puzzle solving within what he calls normal science. A stronger argument that it must play a role in research is first motivated by looking to Collins' first hand account of replication in applied physics and then broader considerations of replication in justifying knowledge claims in scientific research. Finally, consideration of an argument from Wittgenstein shows that whatever explicit guidelines can be drawn up to guide judgement the specification of what counts as correctly following them has to remain implicit.Overall, the paper sets out arguments for the claim that even though explicit guidelines and codifications can play a practical role in informing clinical practice, they rest on a body of tacit or implicit skill that is in principle ineliminable. It forms the bedrock of good judgement and unites the integration of research, expertise and values.

  9. Limitations in conduct and reporting of cochrane reviews rarely inhibit the determination of the validity of evidence for clinical decision-making.

    PubMed

    Alper, Brian S; Fedorowicz, Zbys; van Zuuren, Esther J

    2015-08-01

    To determine how often clinical conclusions derived from Cochrane Reviews have uncertain validity due to review conduct and reporting deficiencies. We evaluated 5142 clinical conclusions in DynaMed (an evidence-based point-of-care clinical reference) based on 4743 Cochrane Reviews. Clinical conclusions with level 2 evidence due to shortcomings in the review's conduct or reporting (rather than deficiencies in the underlying evidence) were confirmed by a DynaMed editor and two Cochrane Review authors. Thirty-one Cochrane Reviews (0.65%) had confirmed deficiencies in conduct and reporting as the reason for classifying 37 assessed clinical conclusions (0.72%) as level 2 evidence. In all cases, it was not feasible for the assessors to specify a clear criticism of the studies included in the reviews. The deficiencies were specific to not accounting for dropouts (2) or inadequate assessment and reporting of allocation concealment (11), other specific trial quality criteria (14), or all trial quality criteria (4). Cochrane Reviews provide high-quality assessment and synthesis of evidence, with fewer than 1% of Cochrane Reviews having limitations which hinder the summary of best current evidence for clinical decision-making. We expect this will further decrease following recent Cochrane quality initiatives. © 2015 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.

  10. Apolipoprotein B synthesis inhibition: results from clinical trials.

    PubMed

    Visser, Maartje E; Kastelein, John J P; Stroes, Erik S G

    2010-08-01

    Mipomersen is a second-generation antisense oligonucleotide developed to inhibit the synthesis of apolipoprotein B-100 in the liver. In this review we will summarize the results of recent preclinical and clinical studies addressing safety and low-density lipoprotein-cholesterol (LDL-c) lowering efficacy of this new compound. In phase 3 clinical trials, mipomersen has been shown to significantly reduce LDL-c in patients with homozygous and heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. Injection site reactions, flu-like symptoms and increases in liver transaminases were the main adverse events. A recent safety study, designed to investigate the effects of mipomersen on intrahepatic triglyceride content, failed to show evidence of clinically relevant hepatic steatosis after 13 weeks of treatment. Mipomersen is a new agent to lower LDL-c in patients at increased risk of cardiovascular disease and/or intolerant to statins. Whereas safety concerns have focused on hepatic fat accumulation, to date no evidence of clinically relevant increases of intrahepatic triglyceride content are reported. Ongoing and future studies are eagerly awaited to assess the impact of mipomersen on hepatic triglyceride content after prolonged exposure.

  11. Weighing the evidence: risks and benefits of participatory documentary in corporatized clinics.

    PubMed

    Hansen, Helena

    2013-12-01

    This paper describes the effects of one U.S.-based public psychiatry clinic's shift to a centralized, corporate style of management, in response to pressures to cut expenditures by focusing on "evidence based" treatments. Participant observation research conducted between 2008 and 2012 for a larger study involving 127 interviews with policy makers, clinic managers, clinical practitioners and patients revealed that the shift heralded the decline of arts based therapies in the clinic, and of the social networks that had developed around them. It also inspired a participatory video self-documentary project among art group members, to portray the importance of arts-based therapies and garner public support for such therapies. Group members found a way to take action in the face of unilateral decision making, but experienced subsequent restrictions on clinic activities and discharge of core members from the clinic. The paper ends with a discussion of biopolitics, central legibility through corporate standardization, and the potential and risks of participatory documentaries to resist these trends. Copyright © 2013. Published by Elsevier Ltd.

  12. The Cost of Accumulating Evidence in Perceptual Decision Making

    PubMed Central

    Drugowitsch, Jan; Moreno-Bote, Rubén; Churchland, Anne K.; Shadlen, Michael N.; Pouget, Alexandre

    2012-01-01

    Decision making often involves the accumulation of information over time, but acquiring information typically comes at a cost. Little is known about the cost incurred by animals and humans for acquiring additional information from sensory variables, due, for instance, to attentional efforts. Through a novel integration of diffusion models and dynamic programming, we were able to estimate the cost of making additional observations per unit of time from two monkeys and six humans in a reaction time random dot motion discrimination task. Surprisingly, we find that, the cost is neither zero nor constant over time, but for the animals and humans features a brief period in which it is constant but increases thereafter. In addition, we show that our theory accurately matches the observed reaction time distributions for each stimulus condition, the time-dependent choice accuracy both conditional on stimulus strength and independent of it, and choice accuracy and mean reaction times as a function of stimulus strength. The theory also correctly predicts that urgency signals in the brain should be independent of the difficulty, or stimulus strength, at each trial. PMID:22423085

  13. The INVEST project: investigating the use of evidence synthesis in the design and analysis of clinical trials.

    PubMed

    Clayton, Gemma L; Smith, Isabelle L; Higgins, Julian P T; Mihaylova, Borislava; Thorpe, Benjamin; Cicero, Robert; Lokuge, Kusal; Forman, Julia R; Tierney, Jayne F; White, Ian R; Sharples, Linda D; Jones, Hayley E

    2017-05-15

    When designing and analysing clinical trials, using previous relevant information, perhaps in the form of evidence syntheses, can reduce research waste. We conducted the INVEST (INVestigating the use of Evidence Synthesis in the design and analysis of clinical Trials) survey to summarise the current use of evidence synthesis in trial design and analysis, to capture opinions of trialists and methodologists on such use, and to understand any barriers. Our sampling frame was all delegates attending the International Clinical Trials Methodology Conference in November 2015. Respondents were asked to indicate (1) their views on the use of evidence synthesis in trial design and analysis, (2) their own use during the past 10 years and (3) the three greatest barriers to use in practice. Of approximately 638 attendees of the conference, 106 (17%) completed the survey, half of whom were statisticians. Support was generally high for using a description of previous evidence, a systematic review or a meta-analysis in trial design. Generally, respondents did not seem to be using evidence syntheses as often as they felt they should. For example, only 50% (42/84 relevant respondents) had used a meta-analysis to inform whether a trial is needed compared with 74% (62/84) indicating that this is desirable. Only 6% (5/81 relevant respondents) had used a value of information analysis to inform sample size calculations versus 22% (18/81) indicating support for this. Surprisingly large numbers of participants indicated support for, and previous use of, evidence syntheses in trial analysis. For example, 79% (79/100) of respondents indicated that external information about the treatment effect should be used to inform aspects of the analysis. The greatest perceived barrier to using evidence synthesis methods in trial design or analysis was time constraints, followed by a belief that the new trial was the first in the area. Evidence syntheses can be resource-intensive, but their use in

  14. Accelerated Mutation Accumulation in Asexual Lineages of a Freshwater Snail

    PubMed Central

    Neiman, Maurine; Hehman, Gery; Miller, Joseph T.; Logsdon, John M.; Taylor, Douglas R.

    2010-01-01

    Sexual reproduction is both extremely costly and widespread relative to asexual reproduction, meaning that it must also confer profound advantages in order to persist. One theorized benefit of sex is that it facilitates the clearance of harmful mutations, which would accumulate more rapidly in the absence of recombination. The extent to which ineffective purifying selection and mutation accumulation are direct consequences of asexuality and whether the accelerated buildup of harmful mutations in asexuals can occur rapidly enough to maintain sex within natural populations, however, remain as open questions. We addressed key components of these questions by estimating the rate of mutation accumulation in the mitochondrial genomes of multiple sexual and asexual representatives of Potamopyrgus antipodarum, a New Zealand snail characterized by mixed sexual/asexual populations. We found that increased mutation accumulation is associated with asexuality and occurs rapidly enough to be detected in recently derived asexual lineages of P. antipodarum. Our results demonstrate that increased mutation accumulation in asexuals can differentially affect coexisting and ecologically similar sexual and asexual lineages. The accelerated rate of mutation accumulation observed in asexual P. antipodarum provides some of the most direct evidence to date for a link between asexuality and mutation accumulation and implies that mutational buildup could be rapid enough to contribute to the short-term evolutionary mechanisms that favor sexual reproduction. PMID:19995828

  15. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  16. Primary total hip arthroplasty in Catalonia: What is the clinical evidence that supports our prosthesis?

    PubMed

    Chaverri-Fierro, D; Lobo-Escolar, L; Espallargues, M; Martínez-Cruz, O; Domingo, L; Pons-Cabrafiga, M

    The implementation of National Prostheses Registries allows us to obtain a large amount of data and make conclusions in order to improve the use of them. Sweden was the first country to implement a National Prostheses Registry in 1979. Catalonia has been doing this since 2005. The aim of our study is to analyse the evidence that supports primary total hip replacement in Catalonia in the last 9 years, based on the Arthroplasty Registry of Catalonia (RACat). A review of the literature was carried out of the prosthesis (acetabular cups/stems) reported in the RACat between the period 2005 to 2013 in the following databases: ODEP (Orthopaedic Data Evaluation Panel), TRIP database, PubMed, and Google Scholar. Those prostheses implanted in less than 10 units (182 acetabular components corresponding to 49 models/228 stems corresponding to 63 models) were excluded. A total of 18,634 (99%) implanted acetabular cups were analysed out of a total number of 18,816, corresponding to 74 different models. In 18 models (2527 acetabular cups) no clinical evidence to support its use was found. An analysis was performed on 19,367 (98.84%) out of a total number of 19,595 implanted stems, corresponding to 75 different models. In 16 models (1845 stems) no clinical evidence was found to support their use. Variable evidence was found in the 56 models of acetabular cups (16,107) and 59 models of stems (17,522), most of it corresponding to level iv clinical evidence. There was a significant number implanted prostheses evaluated (13.56% acetabular cups/9.5% stems) for which no clinical evidence was found. The elevated number of models is highlighted (49 types for acetabular cups/63 types for stems) with less than 10 units implanted, which corresponds to only 1% of the total implants. The use of arthroplasty registers is shown to be an extremely helpful tool that allows analyses and conclusions to be made for the follow-up and post-marketing surveillance period. Copyright © 2016 SECOT

  17. Are Evidence Standards Different for Genomic- vs. Clinical-Based Precision Medicine? A Quantitative Analysis of Individualized Warfarin Therapy.

    PubMed

    Dhanda, D S; Guzauskas, G F; Carlson, J J; Basu, A; Veenstra, D L

    2017-11-01

    Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics: value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic vs. amiodarone-warfarin drug-drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research. Over the past decade, the EVPI for the pharmacogenomic strategy decreased from $1,550 to $140 vs. $1,220 to $280 per patient for the drug-interaction strategy. Evidence levels thus appear to be higher for pharmacogenomic-guided vs. drug-interaction-guided warfarin dosing. Clinical guidelines and reimbursement policies for warfarin PM could be informed by these findings. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  18. Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

    PubMed

    Petersen, Tom; Laslett, Mark; Juhl, Carsten

    2017-05-12

    Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only

  19. What do evidence-based secondary journals tell us about the publication of clinically important articles in primary healthcare journals?

    PubMed Central

    McKibbon, Kathleen Ann; Wilczynski, Nancy L; Haynes, Robert Brian

    2004-01-01

    Background We conducted this analysis to determine i) which journals publish high-quality, clinically relevant studies in internal medicine, general/family practice, general practice nursing, and mental health; and ii) the proportion of clinically relevant articles in each journal. Methods We performed an analytic survey of a hand search of 170 general medicine, general healthcare, and specialty journals for 2000. Research staff assessed individual articles by using explicit criteria for scientific merit for healthcare application. Practitioners assessed the clinical importance of these articles. Outcome measures were the number of high-quality, clinically relevant studies published in the 170 journal titles and how many of these were published in each of four discipline-specific, secondary "evidence-based" journals (ACP Journal Club for internal medicine and its subspecialties; Evidence-Based Medicine for general/family practice; Evidence-Based Nursing for general practice nursing; and Evidence-Based Mental Health for all aspects of mental health). Original studies and review articles were classified for purpose: therapy and prevention, screening and diagnosis, prognosis, etiology and harm, economics and cost, clinical prediction guides, and qualitative studies. Results We evaluated 60,352 articles from 170 journal titles. The pass criteria of high-quality methods and clinically relevant material were met by 3059 original articles and 1073 review articles. For ACP Journal Club (internal medicine), four titles supplied 56.5% of the articles and 27 titles supplied the other 43.5%. For Evidence-Based Medicine (general/family practice), five titles supplied 50.7% of the articles and 40 titles supplied the remaining 49.3%. For Evidence-Based Nursing (general practice nursing), seven titles supplied 51.0% of the articles and 34 additional titles supplied 49.0%. For Evidence-Based Mental Health (mental health), nine titles supplied 53.2% of the articles and 34 additional

  20. Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.

    PubMed

    Farmakis, Dimitrios; Alvarez, Julian; Gal, Tuvia Ben; Brito, Dulce; Fedele, Francesco; Fonseca, Candida; Gordon, Anthony C; Gotsman, Israel; Grossini, Elena; Guarracino, Fabio; Harjola, Veli-Pekka; Hellman, Yaron; Heunks, Leo; Ivancan, Visnja; Karavidas, Apostolos; Kivikko, Matti; Lomivorotov, Vladimir; Longrois, Dan; Masip, Josep; Metra, Marco; Morelli, Andrea; Nikolaou, Maria; Papp, Zoltán; Parkhomenko, Alexander; Poelzl, Gerhard; Pollesello, Piero; Ravn, Hanne Berg; Rex, Steffen; Riha, Hynek; Ricksten, Sven-Erik; Schwinger, Robert H G; Vrtovec, Bojan; Yilmaz, M Birhan; Zielinska, Marzenna; Parissis, John

    2016-11-01

    Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Evidence-based emergency medicine. Creating a system to facilitate translation of evidence into standardized clinical practice: a preliminary report.

    PubMed

    Wright, Stewart W; Trott, Alexander; Lindsell, Christopher J; Smith, Carol; Gibler, W Brian

    2008-01-01

    The Institute of Medicine, through its landmark report concerning errors in medicine, suggests that standardization of practice through systematic development and implementation of evidence-based clinical pathways is an effective way of reducing errors in emergency systems. The specialty of emergency medicine is well positioned to develop a complete system of innovative quality improvement, incorporating best practice guidelines with performance measures and practitioner feedback mechanisms to reduce errors and therefore improve quality of care. This article reviews the construction, ongoing development, and initial impact of such a system at a large, urban, university teaching hospital and at 2 affiliated community hospitals. The Committee for Procedural Quality and Evidence-Based Practice was formed within the Department of Emergency Medicine to establish evidence-based guidelines for nursing and provider care. The committee measures the effect of such guidelines, along with other quality measures, through pre- and postguideline patient care medical record audits. These measures are fed back to the providers in a provider-specific, peer-matched "scorecard." The Committee for Procedural Quality and Evidence-Based Practice affects practice and performance within our department. Multiple physician and nursing guidelines have been developed and put into use. Using asthma as an example, time to first nebulizer treatment and time to disposition from the emergency department decreased. Initial therapeutic agent changed and documentation improved. A comprehensive, guideline-driven, evidence-based approach to clinical practice is feasible within the structure of a department of emergency medicine. High-level departmental support with dedicated personnel is necessary for the success of such a system. Internet site development (available at http://www.CPQE.com) for product storage has proven valuable. Patient care has been improved in several ways; however, consistent and

  2. A systematic review of evidence on the links between patient experience and clinical safety and effectiveness

    PubMed Central

    Doyle, Cathal; Lennox, Laura; Bell, Derek

    2013-01-01

    Objective To explore evidence on the links between patient experience and clinical safety and effectiveness outcomes. Design Systematic review. Setting A wide range of settings within primary and secondary care including hospitals and primary care centres. Participants A wide range of demographic groups and age groups. Primary and secondary outcome measures A broad range of patient safety and clinical effectiveness outcomes including mortality, physical symptoms, length of stay and adherence to treatment. Results This study, summarising evidence from 55 studies, indicates consistent positive associations between patient experience, patient safety and clinical effectiveness for a wide range of disease areas, settings, outcome measures and study designs. It demonstrates positive associations between patient experience and self-rated and objectively measured health outcomes; adherence to recommended clinical practice and medication; preventive care (such as health-promoting behaviour, use of screening services and immunisation); and resource use (such as hospitalisation, length of stay and primary-care visits). There is some evidence of positive associations between patient experience and measures of the technical quality of care and adverse events. Overall, it was more common to find positive associations between patient experience and patient safety and clinical effectiveness than no associations. Conclusions The data presented display that patient experience is positively associated with clinical effectiveness and patient safety, and support the case for the inclusion of patient experience as one of the central pillars of quality in healthcare. It supports the argument that the three dimensions of quality should be looked at as a group and not in isolation. Clinicians should resist sidelining patient experience as too subjective or mood-oriented, divorced from the ‘real’ clinical work of measuring safety and effectiveness. PMID:23293244

  3. Evidence to Support Tooth Brushing in Critically Ill Patients

    PubMed Central

    Ames, Nancy J.

    2012-01-01

    Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully. PMID:21532045

  4. Evidence to support tooth brushing in critically ill patients.

    PubMed

    Ames, Nancy J

    2011-05-01

    Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully.

  5. A pragmatic evidence-based clinical management algorithm for burning mouth syndrome

    PubMed Central

    Yoo, Timothy; Han, Peter; Liu, Yuan; Inman, Jared C.

    2018-01-01

    Background Burning mouth syndrome is a poorly understood disease process with no current standard of treatment. The goal of this article is to provide an evidence-based, practical, clinical algorithm as a guideline for the treatment of burning mouth syndrome. Material and Methods Using available evidence and clinical experience, a multi-step management algorithm was developed. A retrospective cohort study was then performed, following STROBE statement guidelines, comparing outcomes of patients who were managed using the algorithm and those who were managed without. Results Forty-seven patients were included in the study, with 21 (45%) managed using the algorithm and 26 (55%) managed without. The mean age overall was 60.4 ±16.5 years, and most patients (39, 83%) were female. Cohorts showed no statistical difference in age, sex, overall follow-up time, dysgeusia, geographic tongue, or psychiatric disorder; xerostomia, however, was significantly different, skewed toward the algorithm group. Significantly more non-algorithm patients did not continue care (69% vs. 29%, p=0.001). The odds ratio of not continuing care for the non-algorithm group compared to the algorithm group was 5.6 [1.6, 19.8]. Improvement in pain was significantly more likely in the algorithm group (p=0.001), with an odds ratio of 27.5 [3.1, 242.0]. Conclusions We present a basic clinical management algorithm for burning mouth syndrome which may increase the likelihood of pain improvement and patient follow-up. Key words:Burning mouth syndrome, burning tongue, glossodynia, oral pain, oral burning, therapy, treatment. PMID:29750091

  6. Connecting Education to Quality: Engaging Medical Students in the Development of Evidence-Based Clinical Decision Support Tools.

    PubMed

    Crabtree, Elizabeth A; Brennan, Emily; Davis, Amanda; Squires, Jerry E

    2017-01-01

    Evidence-based practice (EBP) skills are crucial for delivering high-quality patient care. It is essential that medical students learn EBP concepts through a practical, in-depth research project. To date, literature on preparing students in this manner is limited. In academic year 2014-2015, the Medical University of South Carolina's (MUSC's) Center for Evidence-Based Practice (now known as the Value Institute) partnered with College of Medicine faculty to revitalize the undergraduate medical student EBP curriculum. Without adding to the number of the lecture hours, the curriculum was restructured to be more process driven, project based, and clinically relevant. The resulting yearlong EBP course partnered small teams of medical students with interprofessional clinical teams to engage the students in developing evidence-based clinical decision support tools. The content developed during the EBP projects is currently being used to develop evidence-based clinical practice guidelines and accompanying order sets. It is likely that this model will serve as a new framework for guideline development and will greatly expand the breadth of evidence-based content currently produced and available for clinicians at the MUSC. It would be feasible to offer a similar course within the MUSC to other disciplines and colleges, or at other institutions, if there were support from administration, interest on the part of clinicians and medical faculty, and individuals with the required expertise available to develop the curriculum and facilitate the course. It is worth considering how to improve the course and evaluating opportunities to implement it within other settings.

  7. Clinical translation of photobiomodulation therapy using evidences from precision molecular pathway analyses (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Arany, Praveen

    2017-02-01

    Can `light' be a Drug? To satisfy this definition as a pharmaceutical agent, light must be absorbed and change bodily function. Much evidence from our understanding of our visual cycle and Vitamin D metabolism have all noted this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. The use of lasers and light devices at high doses in dermatology, ophthalmology, oncology and dentistry are now considered mainstream for certain clinical applications such as surgery, skin rejuvenation, ocular and soft tissue recontouring, anti-tumor and anti-microbial photodynamic therapy. In contrast, therapeutic use of low dose biophotonics devices is called Low Level Light / Laser Therapy (LLLT), now termed Photobiomodulation (PBM) Therapy. This therapy is defined as a non-thermal use of non-ionizing forms of electromagnetic radiation to alleviate pain, inflammation, modulating the immune responses and promoting wound healing and tissue regeneration. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, limited mechanistic insights have prevented the development of rigorous, reproducible clinical protocols. This presentation will outline our current efforts at ongoing efforts in our group to assess molecular pathways and precisely define clinical treatment variables to enable clinical translation with PBM therapies.

  8. Atypical femur fractures: a review of the evidence and its implication to clinical practice

    PubMed Central

    Girgis, Christian M.

    2011-01-01

    Whilst bisphosphonates are an established modality in the treatment of osteoporosis, there have been increasing concerns regarding the risk of an unusual form of femur fracture amongst patients receiving bisphosphonates for prolonged periods. These fractures, referred to as ‘atypical’, have been characterized by a number of clinical and radiographic features that distinguish them from ‘typical’ osteoporotic fractures. The evidence base is currently split between a large number of case series demonstrating an association between the occurrence of atypical fractures and bisphosphonate use and several population-based studies that do not confirm such an association. Hence, a degree of uncertainty surrounds this important issue. In this review, we examine the emerging evidence on atypical femur fractures, assess hypotheses on their biomechanical evolution and discuss the wider clinical implications of this phenomenon. PMID:22870488

  9. [A Study of the Evidence-Based Nursing Practice Competence of Nurses and Its Clinical Applications].

    PubMed

    Hsu, Li-Ling; Hsieh, Suh-Ing; Huang, Ya-Hsuan

    2015-10-01

    Nurses must develop competence in evidence-based nursing in order to provide the best practice medical care to patients. Evidence-based nursing uses issue identification, data mining, and information consolidation from the related medical literature to help nurses find the best evidence. Therefore, for medical institutions to provide quality clinical care, it is necessary for nurses to develop competence in evidence-based nursing. This study aims to explore the effect of a fundamental evidence-based nursing course, as a form of educational intervention, on the development of evidence-based nursing knowledge, self-efficacy in evidence-based practice activities, and outcome expectations of evidence-based practice in nurse participants. Further the competence of these nurses in overcoming obstacles in evidence-based nursing practice. This quasi-experimental study used a pre-post test design with a single group of participants. A convenience sample of 34 nurses from a municipal hospital in northern Taiwan received 8 hours of a fundamental evidence-based nursing course over a two-week period. Participants were asked to complete four questionnaires before and after the intervention. The questionnaires measured the participants' basic demographics, experience in mining the medical literature, evidence-based nursing knowledge, self-efficacy in evidence-based practice activities, outcome expectations of evidence-based practice, competence in overcoming obstacles in evidence-based nursing practice, and learning satisfaction. Collected data was analyzed using paired t, Wilcoxon Signed Rank, and McNemar tests to measure the differences among participants' evidence-based nursing knowledge and practice activities before and after the workshop. The nurses demonstrated significantly higher scores from pre-test to post-test in evidence-based nursing knowledge II, self-efficacy in evidence-based nursing practice activities, and outcome expectations of evidence-based practice

  10. Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials

    PubMed Central

    Bekelman, Justin E.; Deye, James A.; Vikram, Bhadrasain; Bentzen, Soren M.; Bruner, Deborah; Curran, Walter J.; Dignam, James; Efstathiou, Jason A.; FitzGerald, T. J.; Hurkmans, Coen; Ibbott, Geoffrey S.; Lee, J. Jack; Merchant, Timothy E.; Michalski, Jeff; Palta, Jatinder R.; Simon, Richard; Ten Haken, Randal K.; Timmerman, Robert; Tunis, Sean; Coleman, C. Norman; Purdy, James

    2012-01-01

    Background In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute (NCI) sponsored a two day workshop to examine the challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. Lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities like proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: 1) Develop a tiered (and more efficient) system for radiotherapy QA and tailor intensity of QA to clinical trial objectives. Tiers include (i) general credentialing, (ii) trial specific credentialing, and (iii) individual case review; 2) Establish a case QA repository; 3) Develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and 4) Explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA may impact clinical trial accrual, cost, outcomes and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. PMID:22425219

  11. First evidence of an extensive Acheulean large cutting tool accumulation in Europe from Porto Maior (Galicia, Spain).

    PubMed

    Méndez-Quintas, E; Santonja, M; Pérez-González, A; Duval, M; Demuro, M; Arnold, L J

    2018-02-15

    We describe a European Acheulean site characterised by an extensive accumulation of large cutting tools (LCT). This type of Lower Paleolithic assemblage, with dense LCT accumulations, has only been found on the African continent and in the Near East until now. The identification of a site with large accumulations of LCTs favours the hypothesis of an African origin for the Acheulean of Southwest Europe. The lithic tool-bearing deposits date back to 293-205 thousand years ago. Our chronological findings confirm temporal overlap between sites with clear "African" Acheulean affinities and Early Middle Paleolithic sites found elsewhere in the region. These complex technological patterns could be consistent with the potential coexistence of different human species in south-western Europe during the Middle Pleistocene.

  12. Nurse clinic versus home delivery of evidence-based community leg ulcer care: A randomized health services trial

    PubMed Central

    Harrison, Margaret B; Graham, Ian D; Lorimer, Karen; VandenKerkhof, Elizabeth; Buchanan, Maureen; Wells, Phil S; Brandys, Tim; Pierscianowski, Tadeusz

    2008-01-01

    Background International studies report that nurse clinics improve healing rates for the leg ulcer population. However, these studies did not necessarily deliver similar standards of care based on evidence in the treatment venues (home and clinic). A rigorous evaluation of home versus clinic care is required to determine healing rates with equivalent care and establish the acceptability of clinic-delivered care. Methods Health Services RCT was conducted where mobile individuals were allocated to either home or nurse clinic for leg ulcer management. In both arms, care was delivered by specially trained nurses, following an evidence protocol. Primary outcome: 3-month healing rates. Secondary outcomes: durability of healing (recurrence), time free of ulcers, HRQL, satisfaction, resource use. Data were collected at base-line, every 3 months until healing occurred, with 1 year follow-up. Analysis was by intention to treat. Results 126 participants, 65 randomized to receive care in their homes, 61 to nurse-run clinics. No differences found between groups at baseline on socio-demographic, HRQL or clinical characteristics. mean age 69 years, 68% females, 84% English-speaking, half with previous episode of ulceration, 60% ulcers at inclusion < 5 cm2 for < 6 months. No differences in 3-month healing rates: clinic 58.3% compared to home care at 56.7% (p = 0.5) or in secondary outcomes. Conclusion Our findings indicate that organization of care not the setting where care is delivered influences healing rates. Key factors are a system that supports delivery of evidence-based recommendations with care being provided by a trained nursing team resulting in equivalent healing rates, HRQL whether care is delivered in the home or in a community nurse-led clinic. Trial registration ClinicalTrials.gov Protocol Registration System: NCT00656383 PMID:19036149

  13. Weighing the evidence: Risks and benefits of participatory documentary in corporatized clinics

    PubMed Central

    Hansen, Helena

    2014-01-01

    This paper describes the effects of one U.S.-based public psychiatry clinic’s shift to a centralized, corporate style of management, in response to pressures to cut expenditures by focusing on “evidence based” treatments. Participant observation research conducted between 2008 and 2012 for a larger study involving 127 interviews with policy makers, clinic managers, clinical practitioners and patients revealed that the shift heralded the decline of arts based therapies in the clinic, and of the social networks that had developed around them. It also inspired a participatory video self-documentary project among art group members, to portray the importance of arts-based therapies and garner public support for such therapies. Group members found a way to take action in the face of unilateral decision making, but experienced subsequent restrictions on clinic activities and discharge of core members from the clinic. The paper ends with a discussion of biopolitics, central legibility through corporate standardization, and the potential and risks of participatory documentaries to resist these trends. PMID:23932854

  14. Conceptual, Methodological, and Ethical Problems in Communicating Uncertainty in Clinical Evidence

    PubMed Central

    Han, Paul K. J.

    2014-01-01

    The communication of uncertainty in clinical evidence is an important endeavor that poses difficult conceptual, methodological, and ethical problems. Conceptual problems include logical paradoxes in the meaning of probability and “ambiguity”— second-order uncertainty arising from the lack of reliability, credibility, or adequacy of probability information. Methodological problems include questions about optimal methods for representing fundamental uncertainties and for communicating these uncertainties in clinical practice. Ethical problems include questions about whether communicating uncertainty enhances or diminishes patient autonomy and produces net benefits or harms. This article reviews the limited but growing literature on these problems and efforts to address them and identifies key areas of focus for future research. It is argued that the critical need moving forward is for greater conceptual clarity and consistent representational methods that make the meaning of various uncertainties understandable, and for clinical interventions to support patients in coping with uncertainty in decision making. PMID:23132891

  15. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

    PubMed

    Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B

    2017-05-01

    Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  16. Incorporating uncertainty regarding applicability of evidence from meta-analyses into clinical decision making.

    PubMed

    Kriston, Levente; Meister, Ramona

    2014-03-01

    Judging applicability (relevance) of meta-analytical findings to particular clinical decision-making situations remains challenging. We aimed to describe an evidence synthesis method that accounts for possible uncertainty regarding applicability of the evidence. We conceptualized uncertainty regarding applicability of the meta-analytical estimates to a decision-making situation as the result of uncertainty regarding applicability of the findings of the trials that were included in the meta-analysis. This trial-level applicability uncertainty can be directly assessed by the decision maker and allows for the definition of trial inclusion probabilities, which can be used to perform a probabilistic meta-analysis with unequal probability resampling of trials (adaptive meta-analysis). A case study with several fictitious decision-making scenarios was performed to demonstrate the method in practice. We present options to elicit trial inclusion probabilities and perform the calculations. The result of an adaptive meta-analysis is a frequency distribution of the estimated parameters from traditional meta-analysis that provides individually tailored information according to the specific needs and uncertainty of the decision maker. The proposed method offers a direct and formalized combination of research evidence with individual clinical expertise and may aid clinicians in specific decision-making situations. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Perspectives on research evidence and clinical practice: a survey of Australian physiotherapists.

    PubMed

    Grimmer-Somers, Karen; Lekkas, Peter; Nyland, Leah; Young, Alexandra; Kumar, Saravana

    2007-09-01

    Physiotherapists' use of research evidence with clinical decision-making has interested researchers world-wide since 1980; however, little is known about such practices in Australia. The present survey sought information on Australian physiotherapists' perceptions of the importance of research, and barriers to uptake of evidence in clinical practice, when compared with an international cohort from 2001. An Australian-relevant version of an English (UK) National Health Service (NHS) survey instrument was used to canvass 453 physiotherapists, randomly selected from the South Australian Physiotherapy Registration Board 2004-2005 records. The first survey was mailed in August 2005, a reminder was sent two weeks later to non-responders and a follow-up survey was sent in April 2006 to non-responders whose addresses had changed since 2005. There was a 51% response rate. Of the non-responders, 12% were not contactable at their listed address, highlighting the mobility of Australian physiotherapists. Most respondents had undertaken research as students (59.5%) or as students and clinicians (11.5%). Of these, 37.1% were encouraged to embark on more research, and 20.5% were discouraged. The significant predictors of positive perceived importance of research were: previous research experience; being positive about undertaking further research; working in hospitals and holding a postgraduate degree. Clinicians working privately were significantly less likely than managers to be positive about research importance. The only significant predictor for not perceiving barriers to uptake of evidence was being positive about undertaking future research. The study identified constraints on uptake of evidence into practice that were related to accessing, reading and interpreting published research, and implementing findings. Found consistently across employment categories were barriers relating to lack of time, uncertainty about what the research reported, scepticism about the value of

  18. Disease-associated protein seeding suggests a dissociation between misfolded protein accumulation and neurodegeneration in prion disease

    PubMed Central

    Alibhai, James; Diack, Abigail; Manson, Jean

    2017-01-01

    ABSTRACT Chronic neurodegenerative diseases, such as prion diseases or Alzheimer's disease, are associated with progressive accumulation of host proteins which misfold and aggregate. Neurodegeneration is restricted to specific neuronal populations which show clear accumulation of misfolded proteins, whilst neighbouring neurons remain unaffected. Such data raise interesting questions about the vulnerability of specific neuronal populations to neurodegeneration and much research has concentrated only on the mechanisms of neurodegeneration in afflicted neuronal populations. An alternative, undervalued and almost completely unstudied question however is how and why neuronal populations are resilient to neurodegeneration. One potential answer is unaffected regions do not accumulate misfolded proteins, thus mechanisms of neurodegeneration do not become activated. In this perspectives, we discuss novel data from our laboratories which demonstrate that misfolded proteins do accumulate in regions of the brain which do not show evidence of neurodegeneration and further evidence that microglial responses may define the severity of neurodegeneration. PMID:29023184

  19. Attitudes, knowledge and behavior of Japanese physical therapists with regard to evidence-based practice and clinical practice guidelines: a cross-sectional mail survey

    PubMed Central

    Fujimoto, Shuhei; Kon, Noriko; Takasugi, Jun; Nakayama, Takeo

    2017-01-01

    [Purpose] This study aimed to investigate Japanese physical therapists’ attitudes of evidence-based practice and clinical practice guidelines. [Subjects and Methods] In 2014, a cross-sectional postal mail survey using a self-administered questionnaire was conducted. Of 2,982 physical therapists belonging to the Chiba Prefecture Physical Therapist Association, 1,000 were randomly selected. The questionnaire comprised 42 items pertaining to the attitudes of and behavior toward evidence-based practice and clinical practice guidelines. It was investigated to reveal the relationship between clinical practice guidelines/evidence-based practice and therapist characteristics. [Results] The response rate was 39.6%, and 384 questionnaires were available. The main results were as follows: 83.3% participants agreed to the importance of evidence-based practice, 77.1% agree to that evidence-based practice supports clinical decision of physical therapists, and about 11% agreed to have been educated about evidence-based practice. Then, 29.2% used, 54.9% agreed to the importance of, and 13.3% agreed to the utility of clinical practice guidelines. An important factor related mostly to a positive attitude, knowledge and behavior of evidence-based practice and clinical practice guidelines was participating in research activities. [Conclusion] Many of physical therapists do not use and understand the importance of clinical practice guidelines. Participating in research activities may partially contribute to improving these conditions. PMID:28265139

  20. Perceptions of Approved Clinical Instructors: Barriers in the Implementation of Evidence-Based Practice

    PubMed Central

    Hankemeier, Dorice A.; Van Lunen, Bonnie L.

    2013-01-01

    Context: As evidence-based practice (EBP) becomes prevalent in athletic training education, the barriers that Approved Clinical Instructors (ACIs) experience in implementing it with students need to be understood. Objective: To investigate barriers ACIs face when implementing EBP concepts in clinical practice and in teaching EBP to professional athletic training students and to investigate the educational emphases to improve the barriers. Design: Qualitative study. Setting: Telephone interviews. Patients or Other Participants: Sixteen ACIs (11 men, 5 women; experience as an athletic trainer = 10 ± 4.7 years, experience as an ACI = 6.81 ± 3.9 years) were interviewed. Data Collection and Analysis: We interviewed each participant by telephone. Interview data were analyzed and coded for common themes and subthemes regarding barriers and educational emphases. Themes were triangulated through multiple-analyst triangulation and interpretive verification. Results: Barriers to EBP incorporation and educational emphasis placed on EBP were the main themes reported. Resources, personnel, and student characteristics were subthemes identified as barriers. Resource barriers included time, equipment, access to current literature, and knowledge. Coworkers, clinicians, and coaches who were unwilling to accept evidence regarding advancements in treatment were identified as personnel barriers. Programmatic improvement and communication improvement were subthemes of the educational emphasis placed on EBP theme. The ACIs reported the need for better integration between the clinical setting and the classroom and expressed the need for EBP to be integrated throughout the athletic training education program. Conclusions: Integration of the classroom and clinical experience is important in advancing ACIs' use of EBP with their students. Collaborative efforts within the clinical and academic program could help address the barriers ACIs face when implementing EBP. This collaboration could

  1. Argumentation and evidence.

    PubMed

    Upshur, R E G; Colak, Errol

    2003-01-01

    This essay explores the role of informal logic and its application in the context of current debates regarding evidence-based medicine. This aim is achieved through a discussion of the goals and objectives of evidence-based medicine and a review of the criticisms raised against evidence-based medicine. The contributions to informal logic by Stephen Toulmin and Douglas Walton are explicated and their relevance for evidence-based medicine is discussed in relation to a common clinical scenario: hypertension management. This essay concludes with a discussion on the relationship between clinical reasoning, rationality, and evidence. It is argued that informal logic has the virtue of bringing explicitness to the role of evidence in clinical reasoning, and brings sensitivity to understanding the role of dialogical context in the need for evidence in clinical decision making.

  2. Finding 'Evidence of Absence' in Medical Notes: Using NLP for Clinical Inferencing.

    PubMed

    Carter, Marjorie E; Divita, Guy; Redd, Andrew; Rubin, Michael A; Samore, Matthew H; Gupta, Kalpana; Trautner, Barbara W; Gundlapalli, Adi V

    2016-01-01

    Extracting evidence of the absence of a target of interest from medical text can be useful in clinical inferencing. The purpose of our study was to develop a natural language processing (NLP) pipelineto identify the presence of indwelling urinary catheters from electronic medical notes to aid in detection of catheter-associated urinary tract infections (CAUTI). Finding clear evidence that a patient does not have an indwelling urinary catheter is useful in making a determination regarding CAUTI. We developed a lexicon of seven core concepts to infer the absence of a urinary catheter. Of the 990,391 concepts extractedby NLP from a large corpus of 744,285 electronic medical notes from 5589 hospitalized patients, 63,516 were labeled as evidence of absence.Human review revealed three primary causes for false negatives. The lexicon and NLP pipeline were refined using this information, resulting in outputs with an acceptable false positive rate of 11%.

  3. [Cough and hypoxemia as clinical manifestation of pulmonary alveolar proteinosis. Clinical case report].

    PubMed

    Nieto, Mary; Dicembrino, Manuela; Ferraz, Rubén; Romagnoli, Fernando; Giugno, Hilda; Ernst, Glenda; Siminovich, Monica; Botto, Hugo

    2016-06-01

    Alveolar proteinosis is a rare chronic lung disease, especially in children, characterized by abnormal accumulation of lipoproteins and derived surfactant in the intra-alveolar space that generates a severe reduction of gas exchange. Idiopathic presentation form constitutes over 90% of cases, a phenomenon associated with production of autoimmune antibodies directed at the receptor for granulocyte-macrophage colony-stimulating factor. A case of a girl of 5 years of age treated because of atypical pneumonia with unfavorable evolution due to persistent hypoxemia is presented. The diagnosis is obtained through pathologic examination of lung biopsy by thoracotomy, as treatment is carried out by 17bronchopulmonary bronchoscopy lavages and the patient evidences marked clinical improvement. Sociedad Argentina de Pediatría.

  4. How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular Diseases be Improved?

    PubMed

    Sawata, Hiroshi; Tsutani, Kiichiro

    2011-06-29

    Clinical investigations are important for obtaining evidence to improve medical treatment. Large-scale clinical trials with thousands of participants are particularly important for this purpose in cardiovascular diseases. Conducting large-scale clinical trials entails high research costs. This study sought to investigate global trends in large-scale clinical trials in cardiovascular diseases. We searched for trials using clinicaltrials.gov (URL: http://www.clinicaltrials.gov/) using the key words 'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials with 300 or more participants examining cardiovascular diseases. The search revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized controlled trials, 15% involved more than 10,000 participants, and 59% were funded by industry. In RCTs whose results were disclosed, 55% of industry-funded trials and 25% of non-industry funded trials reported statistically significant superiority over control (p = 0.012, 2-sided Fisher's exact test). Our findings highlighted concerns regarding potential bias related to funding sources, and that researchers should be aware of the importance of trial information disclosures and conflicts of interest. We should keep considering management and training regarding information disclosures and conflicts of interest for researchers. This could lead to better clinical evidence and further improvements in the development of medical treatment worldwide.

  5. Do Firms Underinvest in Long-Term Research? Evidence from Cancer Clinical Trials.

    PubMed

    Budish, Eric; Roin, Benjamin N; Williams, Heidi

    2015-07-01

    We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials--and hence, project durations--are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinical-trial endpoints, targeted R&D subsidies, and patent design.

  6. Five-month-old infants have expectations for the accumulation of nonsolid substances.

    PubMed

    Anderson, Erin M; Hespos, Susan J; Rips, Lance J

    2018-06-01

    Infants fail to represent quantities of non-cohesive substances in paradigms where they succeed with solid objects. Some investigators have interpreted these results as evidence that infants do not yet have representations for substances. More recent research, however, shows that 5-month-old infants expect objects and substances to behave and interact in different ways. In the present experiments, we test whether infants have expectations for substances when the outcomes are not simply the opposite of those for objects. In Experiment 1, we find that 5-month-old infants expect that when a cup of sand pours behind a screen, it will accumulate in just one pile rather than two. Similarly, infants expect that when two cups of sand pour in separate streams, two distinct piles will accumulate rather than one. Infants look significantly longer at outcomes with an inconsistent number of piles, providing evidence that infants have expectations for how sand accumulates. To test whether the number of cups or the number of pours guided expectations about accumulation, Experiment 2 placed these cues in conflict. This resulted in chance performance, suggesting that, for infants to build expectations about these outcomes, they need both cues (cup and pour) to converge. These findings offer insight into the nature of infants' representations for non-cohesive substances like sand. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Atelectasis as a cause of postoperative fever: where is the clinical evidence?

    PubMed

    Mavros, Michael N; Velmahos, George C; Falagas, Matthew E

    2011-08-01

    Atelectasis is considered to be the most common cause of early postoperative fever (EPF) but the existing evidence is contradictory. We sought to determine if atelectasis is associated with EPF by analyzing the relevant published evidence. We performed a systematic search in PubMed and Scopus databases to identify studies examining the association between atelectasis and EPF. A total of eight studies, including 998 cardiac, abdominal, and maxillofacial surgery patients, were eligible for analysis. Only two studies specifically examined our question, and six additional articles reported sufficient data to be included. Only one study reported a significant association between postoperative atelectasis and fever, whereas the remaining studies indicated no such association. The performance of EPF as a diagnostic test for atelectasis was also assessed, and EPF performed poorly (pooled diagnostic OR, 1.40; 95% CI, 0.92-2.12). The significant heterogeneity among the studies precluded a formal metaanalysis. The available evidence regarding the association of atelectasis and fever is scarce. We found no clinical evidence supporting the concept that atelectasis is associated with EPF. More so, there is no clear evidence that atelectasis causes fever at all. Large studies are needed to precisely evaluate the contribution of atelectasis in EPF.

  8. [Clinical applicability of evidence-based orthopedics--a cross-sectional study of the quality of orthopedic evidence].

    PubMed

    Vavken, P; Culen, G; Dorotka, R

    2008-01-01

    The demand to routinely apply evidence-based methods in orthopedic surgery increases steadily. In order to do so, however, the validity and reliability of the "evidence" has to be scrutinized. The object of this study was to assess the quality of the most recent orthopedic evidence and to determine variables that have an influence on quality. All 2006 controlled trials from orthopedic journals with high impact factors were analysed in a cross-sectional study. A score based on the CONSORT statement was used to assess study quality. Selected variables were tested for their influence on the quality of the study. Two independent blinded observers reviewed 126 studies. The overall quality was moderate to high. The most neglected parameters were power analysis, intention-to-treat, and concealment. The participation of a methodologically trained investigator increases study quality significantly. There was no difference in study quality irrespective of whether or not there was statistically significant result. Using our quality score we were able show fairly good results for recent orthopedic studies. The most frequently neglected issues in orthopedic research are blinding, power analysis, and intention-to-treat. This may distort the results of clinical investigations considerably and, especially, lack of concealment causes false-positive findings. Our data show furthermore that participation of a methodologist significantly increases quality of the study and consequently strengthens the reliability of results.

  9. Predicting Regional Pattern of Longitudinal β-Amyloid Accumulation by Baseline PET.

    PubMed

    Guo, Tengfei; Brendel, Matthias; Grimmer, Timo; Rominger, Axel; Yakushev, Igor

    2017-04-01

    Knowledge about spatial and temporal patterns of β-amyloid (Aβ) accumulation is essential for understanding Alzheimer disease (AD) and for design of antiamyloid drug trials. Here, we tested whether the regional pattern of longitudinal Aβ accumulation can be predicted by baseline amyloid PET. Methods: Baseline and 2-y follow-up 18 F-florbetapir PET data from 58 patients with incipient and manifest dementia due to AD were analyzed. With the determination of how fast amyloid deposits in a given region relative to the whole-brain gray matter, a pseudotemporal accumulation rate for each region was calculated. The actual accumulation rate of 18 F-florbetapir was calculated from follow-up data. Results: Pseudotemporal measurements from baseline PET data explained 87% ( P < 0.001) of the variance in longitudinal accumulation rate across 62 regions. The method accurately predicted the top 10 fast and slow accumulating regions. Conclusion: Pseudotemporal analysis of baseline PET images is capable of predicting the regional pattern of longitudinal Aβ accumulation in AD at a group level. This approach may be useful in exploring spatial patterns of Aβ accumulation in other amyloid-associated disorders such as Lewy body disease and atypical forms of AD. In addition, the method allows identification of brain regions with a high accumulation rate of Aβ, which are of particular interest for antiamyloid clinical trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Preserving residual renal function in dialysis patients: an update on evidence to assist clinical decision making

    PubMed Central

    Jensen, Jens Dam; Peters, Christian Daugaard; Jespersen, Bente

    2011-01-01

    It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice. PMID:25949486

  11. Role of Ambulatory and Home Blood Pressure Monitoring in Clinical Practice: A Narrative Review

    PubMed Central

    Shimbo, Daichi; Abdalla, Marwah; Falzon, Louise; Townsend, Raymond R.; Muntner, Paul

    2015-01-01

    Hypertension, a common cardiovascular disease (CVD) risk factor, is usually diagnosed and treated based on blood pressure readings obtained in the clinic setting. Blood pressure may differ considerably when measured in the clinic versus outside of the clinic setting. Over the past several decades, evidence has accumulated on two approaches for measuring out-of-clinic blood pressure: ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM). Blood pressure measures on ABPM and HBPM each have a stronger association with CVD outcomes than clinic blood pressure. Controversy exists whether ABPM or HBPM is superior for estimating CVD risk, and under what circumstances these methods should be used in clinical practice for assessing out-of-clinic blood pressure. This review describes ABPM and HBPM procedures, the blood pressure phenotypic measures that can be ascertained, and the evidence that supports the use of each approach to measure out-of-clinic blood pressure. This review also describes barriers to the successful implementation of ABPM and HBPM in clinical practice, proposes core competencies for the conduct of these procedures, and highlights important areas for future research. PMID:26457954

  12. Swallowing and Dysphagia Rehabilitation: Translating Principles of Neural Plasticity into Clinically Oriented Evidence

    ERIC Educational Resources Information Center

    Robbins, JoAnne; Butler, Susan G.; Daniels, Stephanie K.; Gross, Roxann Diez; Langmore, Susan; Lazarus, Cathy L.; Martin-Harris, Bonnie; McCabe, Daniel; Musson, Nan; Rosenbek, John

    2008-01-01

    Purpose: This review presents the state of swallowing rehabilitation science as it relates to evidence for neural plastic changes in the brain. The case is made for essential collaboration between clinical and basic scientists to expand the positive influences of dysphagia rehabilitation in synergy with growth in technology and knowledge. The…

  13. Clinical Teachers' Attitudes toward the Efficacy of Evidence-Based Medicine Workshop and Self-Reported Ability in Evidence-Based Practice in Iran

    ERIC Educational Resources Information Center

    Kouhpayehzadeh, Jalil; Baradaran, Hamid; Arabshahi, Kamran Soltani; Knill-Jones, Robin

    2006-01-01

    Introduction: Evidence-based medicine (EBM) has been introduced in medical schools worldwide, but there is little known about effective methods for teaching EBM skills, particularly in developing countries. This study assesses the impact of an EBM workshop on clinical teachers' attitudes and use of EBM skills. Methods: Seventy-two clinical…

  14. Anthocyanins facilitate tungsten accumulation in Brassica

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hale, K.L.

    2002-11-01

    Accumulation of molybdenum in Brassica was recently found to be correlated with anthocyanin content, involving the formation of a blue complex. Here the role of anthocyanins in tungsten sequestration was investigated using three species of Brassica: B. rapa (cv. Fast plants), B. juncea (Indian mustard) and B. oleracea (red cabbage). Seedlings of B. rapa and B. juncea turned blue when supplied with colourless tungstate. The blue compound co-localized with anthocyanins in the peripheral cell layers, and the degree of blueness was correlated with anthocyanin content. The direct involvement of anthocyanins in the blue coloration was evident when purified anthocyanins showedmore » a colour change from pink to blue in vitro upon addition of tungstate, over a wide pH range. Anthocyanin production was upregulated 3-fold by W in B. juncea, possibly reflecting a function for anthocyanins in W tolerance or sequestration. The presence of anthocyanins facilitated W accumulation in B. rapa: anthocyanin-containing seedlings accumulated 3-fold more W than an anthocyaninless mutant. There was no correlation between anthocyanin content and W tolerance under these conditions. The nature of the interaction between anthocyanins and tungstate was investigated. X-ray absorption spectroscopy showed no change in the local chemical environment of Wupon uptake of tungstate by the plant; HPLC analysis of purified anthocyanin with or without tungstate showed no peak shift after metal treatment.« less

  15. Rendering clinical psychology an evidence-based scientific discipline: a case study.

    PubMed

    St Stoyanov, Drozdstoj; Machamer, Peter K; Schaffner, Kenneth F

    2012-02-01

    Both modern neuroscience and clinical psychology taken as separate fields have failed to reveal the explanatory mechanisms underlying mental disorders. The evidence acquired inside the mono-disciplinary matrices of neurobiology, clinical psychology and psychopathology are deeply insufficient in terms of their validity, reliability and utility. Further, no effective trans-disciplinary connections have been developed between them. In this context, our case study aims at illustrating some specific facets of clinical psychology as a crucial discipline for explaining and understanding mental disorder. The methods employed in clinical psychology are scrutinized using the exemplar case of the Minnesota Multiphasic Personality Inventory (MMPI). We demonstrate that a clinical interview and a clinical psychological rating scale consist of the same kind of cognitive content. The provisional difference can be described in terms of its having two comparable complementary cognitive structures. The test is composed of self-evaluation reports (items) formulated as questions or statements. The psychopathological structured interview is formulated in terms of subjective experience indicated as symptoms (these are self-reports recorded by the physician), complemented with the so-called 'signs' or the presumably 'objective' observations of the overt behaviours of the patient. However, the cognitive content of clinical judgment is beyond any doubt as subjective as the narrative of the patient. None of the components of the structured psychopathological interview is independent of the inter-subjective system created in the situation of clinical assessment. Therefore, the protocols from various clinicians that serve to sustain the reliability claim of the 'scientific' Diagnostic Statistical Manual of Mental Disorders cannot be regarded as independent measurements of the cognitive content and value of the psychological rating scales or vice versa. © 2011 Blackwell Publishing Ltd.

  16. Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features

    PubMed Central

    Tamayo, Pablo; Cho, Yoon-Jae; Tsherniak, Aviad; Greulich, Heidi; Ambrogio, Lauren; Schouten-van Meeteren, Netteke; Zhou, Tianni; Buxton, Allen; Kool, Marcel; Meyerson, Matthew; Pomeroy, Scott L.; Mesirov, Jill P.

    2011-01-01

    Purpose Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. Patients and Methods A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78). Results On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse. Conclusion The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification. PMID:21357789

  17. Dental wax decreases calculus accumulation in small dogs.

    PubMed

    Smith, Mark M; Smithson, Christopher W

    2014-01-01

    A dental wax was evaluated after unilateral application in 20 client-owned, mixed and purebred small dogs using a clean, split-mouth study model. All dogs had clinical signs of periodontal disease including plaque, calculus, and/or gingivitis. The wax was randomly applied to the teeth of one side of the mouth daily for 30-days while the contralateral side received no treatment. Owner parameters evaluated included compliance and a subjective assessment of ease of wax application. Gingivitis, plaque and calculus accumulation were scored at the end of the study period. Owners considered the wax easy to apply in all dogs. Compliance with no missed application days was achieved in 8 dogs. The number of missed application days had no effect on wax efficacy. There was no significant difference in gingivitis or plaque accumulation scores when comparing treated and untreated sides. Calculus accumulation scores were significantly less (22.1 %) for teeth receiving the dental wax.

  18. Evidence and evidence gaps - an introduction.

    PubMed

    Dreier, Gabriele; Löhler, Jan

    2016-01-01

    Background: Medical treatment requires the implementation of existing evidence in the decision making process in order to be able to find the best possible diagnostic, therapeutic or prognostic measure for the individual patient based on the physician's own expertise. Clinical trials form the evidence base and ideally, their results are assembled, analyzed, summarized, and made available in systematic review articles. Beside planning, conducting, and evaluating clinical trials in conformity with GCP (good clinical practice), it is essential that all results of conducted studies are publicly available in order to avoid publication bias. This includes also the public registration of planned and cancelled trials. History: During the last 25 years, evidence-based medicine became increasingly important in medical care and research. It is closely associated with the names of Archibald Cochrane and David Sackett. About 15 years ago, the Deutsche Cochrane Zentrum (Cochrane Germany) and the Deutsche Netzwerk Evidenzbasierte Medizin e.V. (German Network for Evidence-based Medicine, DNEbM) were founded in Germany. In the International Cochrane Collaboration, clinicians and methodologists come together on an interdisciplinary level to further develop methods of evidence-based medicine and to discuss the topics of evidence generation and processing as well as knowledge transfer. Problem: Evidence is particularly important for physicians in the process of decision making, however, at the same time it is the base of a scientific proof of benefit for the patient and finally for the payers in health care. The closure of evidence gaps requires enormously high staff and financial resources, significant organizational efforts, and it is only successful when clinical and methodical expertise as well as specific knowledge in the field of clinical research are included. On the other hand, the knowledge has to be transferred into practice. For this purpose, practice guidelines, meetings

  19. Kombucha: a systematic review of the clinical evidence.

    PubMed

    Ernst, E

    2003-04-01

    Kombucha has become a popular complementary remedy. The aim of this systematic review was to critically evaluate the evidence related to its efficacy and safety. Computerised literature searches were carried out to locate all human medical investigations of kombucha regardless of study design. Data were extracted and validated by the present author and are reported in narrative form. No clinical studies were found relating to the efficacy of this remedy. Several case reports and case series raise doubts about the safety of kombucha. They include suspected liver damage, metabolic acidosis and cutaneous anthrax infections. One fatality is on record. On the basis of these data it was concluded that the largely undetermined benefits do not outweigh the documented risks of kombucha. It can therefore not be recommended for therapeutic use. Copyright 2003 S. Karger GmbH, Freiburg

  20. Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

    PubMed Central

    Shahin, Mohamed H.A.; Johnson, Julie A.

    2013-01-01

    Purpose of review To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice. Recent findings Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice. Summary Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics. PMID:23478884

  1. Chiropractic clinical practice guideline: evidence-based treatment of adult neck pain not due to whiplash

    PubMed Central

    Anderson-Peacock, Elizabeth; Blouin, Jean-Sébastien; Bryans, Roland; Danis, Normand; Furlan, Andrea; Marcoux, Henri; Potter, Brock; Ruegg, Rick; Gross Stein, Janice; White, Eleanor

    2005-01-01

    OBJECTIVE To provide an evidence-based clinical practice guideline for the chiropractic cervical treatment of adults with acute or chronic neck pain not due to whiplash. This is a considerable health concern considered to be a priority by stakeholders, and about which the scientific information was poorly organized. OPTIONS Cervical treatments: manipulation, mobilization, ischemic pressure, clinic- and home-based exercise, traction, education, low-power laser, massage, transcutaneous electrical nerve stimulation, pillows, pulsed electromagnetic therapy, and ultrasound. OUTCOMES The primary outcomes considered were improved (reduced and less intrusive) pain and improved (increased and easier) ranges of motion (ROM) of the adult cervical spine. EVIDENCE An “extraction” team recorded evidence from articles found by literature search teams using 4 separate literature searches, and rated it using a Table adapted from the Oxford Centre for Evidence-based Medicine. The searches were 1) Treatment; August, 2003, using MEDLINE, CINAHL, AMED, MANTIS, ICL, The Cochrane Library (includes CENTRAL), and EBSCO, identified 182 articles. 2) Risk management (adverse events); October, 2004, identified 230 articles and 2 texts. 3) Risk management (dissection); September, 2003, identified 79 articles. 4) Treatment update; a repeat of the treatment search for articles published between September, 2003 and November, 2004 inclusive identified 121 articles. VALUES To enable the search of the literature, the authors (Guidelines Development Committee [GDC]) regarded chiropractic treatment as including elements of “conservative” care in the search strategies, but not in the consideration of the range of chiropractic practice. Also, knowledge based only on clinical experience was considered less valid and reliable than good-caliber evidence, but where the caliber of the relevant evidence was low or it was non-existent, unpublished clinical experience was considered to be equivalent to

  2. Evidence-based protocol for structural rehabilitation of the spine and posture: review of clinical biomechanics of posture (CBP®) publications

    PubMed Central

    Oakley, Paul A.; Harrison, Donald D.; Harrison, Deed E.; Haas, Jason W.

    2005-01-01

    BACKGROUND Although practice protocols exist for SMT and functional rehabilitation, no practice protocols exist for structural rehabilitation. Traditional chiropractic practice guidelines have been limited to acute and chronic pain treatment, with limited inclusion of functional and exclusion of structural rehabilitation procedures. OBJECTIVE (1) To derive an evidence-based practice protocol for structural rehabilitation from publications on Clinical Biomechanics of Posture (CBP®) methods, and (2) to compare the evidence for Diversified, SMT, and CBP®. METHODS Clinical control trials utilizing CBP® methods and spinal manipulative therapy (SMT) were obtained from searches in Mantis, CINAHL, and Index Medicus. Using data from SMT review articles, evidence for Diversified Technique (as taught in chiropractic colleges), SMT, and CBP® were rated and compared. RESULTS From the evidence from Clinical Control Trials on SMT and CBP®, there is very little evidence support for Diversified (our rating = 18), as taught in chiropractic colleges, for the treatment of pain subjects, while CBP® (our rating = 46) and SMT for neck pain (rating = 58) and low back pain (our rating = 202) have evidence-based support. CONCLUSIONS While CBP® Technique has approximately as much evidence-based support as SMT for neck pain, CBP® has more evidence to support its methods than the Diversified technique taught in chiropractic colleges, but not as much as SMT for low back pain. The evolution of chiropractic specialization has occurred, and doctors providing structural-based chiropractic care require protocol guidelines for patient quality assurance and standardization. A structural rehabilitation protocol was developed based on evidence from CBP® publications. PMID:17549209

  3. Strain accumulation and rotation in the Eastern California Shear Zone

    USGS Publications Warehouse

    Savage, J.C.; Gan, Weijun; Svarc, J.L.

    2001-01-01

    Although the Eastern California Shear Zone (ECSZ) (strike ???N25??W) does not quite coincide with a small circle drawn about the Pacific-North America pole of rotation, trilateration and GPS measurements demonstrate that the motion within the zone corresponds to right-lateral simple shear across a vertical plane (strike N33??W??5??) roughly parallel to the tangent to that local small circle (strike ???N40??W). If the simple shear is released by slip on faults subparallel to the shear zone, the accumulated rotation is also released, leaving no secular rotation. South of the Garlock fault the principal faults (e.g., Calico-Blackwater fault) strike ???N40??W, close enough to the strike of the vertical plane across which maximum right-lateral shear accumulates to almost wholly accommodate that accumulation of both strain and rotation by right-lateral slip. North of the Garlock fault dip slip as well as strike slip on the principal faults (strike ???N20??W) is required to accommodate the simple shear accumulation. In both cases the accumulated rotation is released with the shear strain. The Garlock fault, which transects the ECSZ, is not offset by north-northwest striking faults nor, despite geological evidence for long-term left-lateral slip, does it appear at the present time to be accumulating left-lateral simple shear strain across the fault due to slip at depth. Rather the motion is explained by right-lateral simple shear across the orthogonal ECSZ. Left-lateral slip on the Garlock fault will release the shear strain accumulating there but would augment the accumulating rotation, resulting in a secular clockwise rotation rate ???80 nrad yr-1 (4.6?? Myr-1).

  4. International lessons in new methods for grading and integrating cost effectiveness evidence into clinical practice guidelines.

    PubMed

    Antioch, Kathryn M; Drummond, Michael F; Niessen, Louis W; Vondeling, Hindrik

    2017-01-01

    Economic evidence is influential in health technology assessment world-wide. Clinical Practice Guidelines (CPG) can enable economists to include economic information on health care provision. Application of economic evidence in CPGs, and its integration into clinical practice and national decision making is hampered by objections from professions, paucity of economic evidence or lack of policy commitment. The use of state-of-art economic methodologies will improve this. Economic evidence can be graded by 'checklists' to establish the best evidence for decision making given methodological rigor. New economic evaluation checklists, Multi-Criteria Decision Analyses (MCDA) and other decision criteria enable health economists to impact on decision making world-wide. We analyse the methodologies for integrating economic evidence into CPG agencies globally, including the Agency of Health Research and Quality (AHRQ) in the USA, National Health and Medical Research Council (NHMRC) and Australian political reforms. The Guidelines and Economists Network International (GENI) Board members from Australia, UK, Canada and Denmark presented the findings at the conference of the International Health Economists Association (IHEA) and we report conclusions and developments since. The Consolidated Guidelines for the Reporting of Economic Evaluations (CHEERS) 24 item check list can be used by AHRQ, NHMRC, other CPG and health organisations, in conjunction with the Drummond ten-point check list and a questionnaire that scores that checklist for grading studies, when assessing economic evidence. Cost-effectiveness Analysis (CEA) thresholds, opportunity cost and willingness-to-pay (WTP) are crucial issues for decision rules in CEA generally, including end-of-life therapies. Limitations of inter-rater reliability in checklists can be addressed by including more than one assessor to reach a consensus, especially when impacting on treatment decisions. We identify priority areas to generate

  5. Bayes factors for the linear ballistic accumulator model of decision-making.

    PubMed

    Evans, Nathan J; Brown, Scott D

    2018-04-01

    Evidence accumulation models of decision-making have led to advances in several different areas of psychology. These models provide a way to integrate response time and accuracy data, and to describe performance in terms of latent cognitive processes. Testing important psychological hypotheses using cognitive models requires a method to make inferences about different versions of the models which assume different parameters to cause observed effects. The task of model-based inference using noisy data is difficult, and has proven especially problematic with current model selection methods based on parameter estimation. We provide a method for computing Bayes factors through Monte-Carlo integration for the linear ballistic accumulator (LBA; Brown and Heathcote, 2008), a widely used evidence accumulation model. Bayes factors are used frequently for inference with simpler statistical models, and they do not require parameter estimation. In order to overcome the computational burden of estimating Bayes factors via brute force integration, we exploit general purpose graphical processing units; we provide free code for this. This approach allows estimation of Bayes factors via Monte-Carlo integration within a practical time frame. We demonstrate the method using both simulated and real data. We investigate the stability of the Monte-Carlo approximation, and the LBA's inferential properties, in simulation studies.

  6. Faculty Training in Evidence-Based Medicine: Improving Evidence Acquisition and Critical Appraisal

    ERIC Educational Resources Information Center

    Nicholson, Laura J.; Warde, Carole M.; Boker, John R.

    2007-01-01

    Introduction: Evidence-based medicine (EBM) integrates published clinical evidence with patient values and clinical expertise, the output of which is informed medical decision making. Key skills for evidence-based practice include acquisition and appraisal of clinical information. Faculty clinicians often lack expertise in these skills and are…

  7. Immunomodulators in SLE: Clinical evidence and immunologic actions

    PubMed Central

    Durcan, L.; Petri, M.

    2016-01-01

    Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible for a significant burden of morbidity, and immunosuppressives which are limited by suboptimal efficacy, increased infections and malignancies. There are significant deficiencies in our immunosuppressive armamentarium, making immunomodulatory therapies crucial, offering the opportunity to prevent disease flare and the subsequent accrual of damage. Currently available immunomodulators include prasterone (synthetic dehydroeipandrosterone), vitamin D, hydroxychloroquine and belimumab. These therapies, acting via numerous cellular and cytokine pathways, have been shown to modify the aberrant immune responses associated with SLE without overt immunosuppression. Vitamin D is important in SLE and supplementation appears to have a positive impact on disease activity particularly proteinuria. Belimumab has specific immunomodulatory properties and is an effective therapy in those with specific serological and clinical characteristics predictive of response. Hydroxychloroquine is a crucial background medication in SLE with actions in many molecular pathways. It has disease specific effects in reducing flare, treating cutaneous disease and inflammatory arthralgias in addition to other effects such as reduced thrombosis, increased longevity, improved lipids, better glycemic control and blood pressure. Dehydroeipandrosterone is also an immunomodulator in SLE which can have positive effects on disease activity and has bone protective properties. This review outlines the immunologic actions of these drugs and the clinical evidence supporting their use. PMID:27371107

  8. Glomerular disease augments kidney accumulation of synthetic anionic polymers.

    PubMed

    Liu, Gary W; Prossnitz, Alexander N; Eng, Diana G; Cheng, Yilong; Subrahmanyam, Nithya; Pippin, Jeffrey W; Lamm, Robert J; Ngambenjawong, Chayanon; Ghandehari, Hamidreza; Shankland, Stuart J; Pun, Suzie H

    2018-06-02

    Polymeric drug carriers can alter the pharmacokinetics of their drug cargoes, thereby improving drug therapeutic index and reducing side effects. Understanding and controlling polymer properties that drive tissue-specific accumulation is critical in engineering targeted drug delivery systems. For kidney disease applications, targeted drug delivery to renal cells that reside beyond the charge- and size-selective glomerular filtration barrier could have clinical potential. However, there are limited reports on polymer properties that might enhance kidney accumulation. Here, we studied the effects of molecular weight and charge on the in vivo kidney accumulation of polymers in health and disease. We synthesized a panel of well-defined polymers by atom transfer radical polymerization to answer several questions. First, the biodistribution of low molecular weight (23-27 kDa) polymers composed of various ratios of neutral:anionic monomers (1:0, 1:1, 1:4) in normal mice was determined. Then, highly anionic (1:4 monomer ratio) low molecular and high molecular weight (47 kDa) polymers were tested in both normal and experimental focal segmental glomerulosclerosis (FSGS) mice, a model that results in loss of glomerular filtration selectivity. Through these studies, we observed that kidney-specific polymer accumulation increases with anionic monomer content, but not molecular weight; experimental FSGS increases kidney accumulation of anionic polymers; and anionic polymers accumulate predominantly in proximal tubule cells, with some distribution in kidney glomeruli. These findings can be applied to the design of polymeric drug carriers to enhance or mitigate kidney accumulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

    PubMed Central

    2012-01-01

    Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

  10. Evidence-Based Practice for Outpatient Clinical Teams

    ERIC Educational Resources Information Center

    Hamilton, John D.

    2006-01-01

    This column focuses on evidence-based practice (EBP) within multidisciplinary outpatient settings, but first provides some definitions. Besides EBP (Burns and Hoagwood, 2005; Guyatt and Rennie, 2002), there are also evidence-based medicine (EBM; March et al., 2005), evidence-based service (EBS; Chorpita et al., 2002), and evidence-based treatment…

  11. Molecular chaperone accumulation as a function of stress evidences adaptation to high hydrostatic pressure in the piezophilic archaeon Thermococcus barophilus.

    PubMed

    Cario, Anaïs; Jebbar, Mohamed; Thiel, Axel; Kervarec, Nelly; Oger, Phil M

    2016-07-05

    The accumulation of mannosyl-glycerate (MG), the salinity stress response osmolyte of Thermococcales, was investigated as a function of hydrostatic pressure in Thermococcus barophilus strain MP, a hyperthermophilic, piezophilic archaeon isolated from the Snake Pit site (MAR), which grows optimally at 40 MPa. Strain MP accumulated MG primarily in response to salinity stress, but in contrast to other Thermococcales, MG was also accumulated in response to thermal stress. MG accumulation peaked for combined stresses. The accumulation of MG was drastically increased under sub-optimal hydrostatic pressure conditions, demonstrating that low pressure is perceived as a stress in this piezophile, and that the proteome of T. barophilus is low-pressure sensitive. MG accumulation was strongly reduced under supra-optimal pressure conditions clearly demonstrating the structural adaptation of this proteome to high hydrostatic pressure. The lack of MG synthesis only slightly altered the growth characteristics of two different MG synthesis deletion mutants. No shift to other osmolytes was observed. Altogether our observations suggest that the salinity stress response in T. barophilus is not essential and may be under negative selective pressure, similarly to what has been observed for its thermal stress response.

  12. Molecular chaperone accumulation as a function of stress evidences adaptation to high hydrostatic pressure in the piezophilic archaeon Thermococcus barophilus

    PubMed Central

    Cario, Anaïs; Jebbar, Mohamed; Thiel, Axel; Kervarec, Nelly; Oger, Phil M.

    2016-01-01

    The accumulation of mannosyl-glycerate (MG), the salinity stress response osmolyte of Thermococcales, was investigated as a function of hydrostatic pressure in Thermococcus barophilus strain MP, a hyperthermophilic, piezophilic archaeon isolated from the Snake Pit site (MAR), which grows optimally at 40 MPa. Strain MP accumulated MG primarily in response to salinity stress, but in contrast to other Thermococcales, MG was also accumulated in response to thermal stress. MG accumulation peaked for combined stresses. The accumulation of MG was drastically increased under sub-optimal hydrostatic pressure conditions, demonstrating that low pressure is perceived as a stress in this piezophile, and that the proteome of T. barophilus is low-pressure sensitive. MG accumulation was strongly reduced under supra-optimal pressure conditions clearly demonstrating the structural adaptation of this proteome to high hydrostatic pressure. The lack of MG synthesis only slightly altered the growth characteristics of two different MG synthesis deletion mutants. No shift to other osmolytes was observed. Altogether our observations suggest that the salinity stress response in T. barophilus is not essential and may be under negative selective pressure, similarly to what has been observed for its thermal stress response. PMID:27378270

  13. Clinical and molecular evidence of the consumption of broccoli, glucoraphanin and sulforaphane in humans.

    PubMed

    Conzatti, Adriana; Fróes, Fernanda Carolina Telles da Silva; Schweigert Perry, Ingrid Dalira; Souza, Carolina Guerini de

    2014-11-30

    Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin (GRA), which is found in great amounts especially in broccoli. Its consumption has been reported to be associated with a lower risk of myocardial infarction and cancer development. Additionally, its effects have been studied in neurodegenerative diseases, diabetes, and atherosclerosis, most of the times using animal models and cell cultures. Given the promising results of SFN, this review aimed to investigate evidence documented in human intervention studies with broccoli, GRA and SFN. A search was performed on PubMed and Virtual Health Library databases by two independent researchers using the descriptors "broccoli" or "glucoraphanin" or "sulforaphane", which should appear on the study's title or abstract. This review included randomized clinical trials performed in humans that were published in English and Portuguese from 2003 to 2013 and that considered clinical and molecular parameters of cell damage as outcomes of interest. Seventeen studies were selected, and the predominant type of intervention was broccoli sprouts. More consistent results were obtained for the clinical parameters blood glucose and lipid profile and for molecular parameters of oxidative stress, indicating that there was an improvement in these parameters after intervention. Less solid evidence was found with regard to decreased inflammation, Helicobacter pylori colonization, and protection against cancer. Although being relevant, the evidence for the use of broccoli, GRA and SFN in humans are limited; thus, further intervention studies are needed to evaluate outcomes more consistently and reach better grounded conclusions. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  14. Clinical research data sharing: what an open science world means for researchers involved in evidence synthesis.

    PubMed

    Ross, Joseph S

    2016-09-20

    The International Committee of Medical Journal Editors (ICMJE) recently announced a bold step forward to require data generated by interventional clinical trials that are published in its member journals to be responsibly shared with external investigators. The movement toward a clinical research culture that supports data sharing has important implications for the design, conduct, and reporting of systematic reviews and meta-analyses. While data sharing is likely to enhance the science of evidence synthesis, facilitating the identification and inclusion of all relevant research, it will also pose key challenges, such as requiring broader search strategies and more thorough scrutiny of identified research. Furthermore, the adoption of data sharing initiatives by the clinical research community should challenge the community of researchers involved in evidence synthesis to follow suit, including the widespread adoption of systematic review registration, results reporting, and data sharing, to promote transparency and enhance the integrity of the research process.

  15. Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical Evidence

    PubMed Central

    Ud-Din, Sara; Bayat, Ardeshir

    2014-01-01

    Electrical stimulation (ES) has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC), alternating current (AC), high-voltage pulsed current (HVPC), low-intensity direct current (LIDC) and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE) for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used. PMID:27429287

  16. From dental science to clinical practice: Knowledge translation and evidence-based dentistry principles.

    PubMed

    Afrashtehfar, Kelvin I; Assery, Mansour K

    2017-07-01

    It has been claimed that in order to decrease the gap between what we know and what we do, research findings must be translated from knowledge to action. Such practices better enable dentists to make evidence-based decisions instead of personal ideas and judgments. To this end, this literature review aims to revisit the concepts of knowledge translation and evidence-based dentistry (EBD) and depict their role and influence within dental education. It addresses some possible strategies to facilitate knowledge translation (KT), encourage dental students to use EBD principles, and to encourage dental educators to create an environment in which students become self-directed learners. It concludes with a call to develop up-to-date and efficient online platforms that could grant dentists better access to EBD sources in order to more efficiently translate research evidence into the clinic.

  17. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence.

    PubMed

    Sarris, Jerome; Panossian, Alexander; Schweitzer, Isaac; Stough, Con; Scholey, Andrew

    2011-12-01

    Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Caco-2 accumulation of lutein is greater from human milk than from infant formula despite similar bioaccessibility.

    PubMed

    Lipkie, Tristan E; Banavara, Dattatreya; Shah, Bhavini; Morrow, Ardythe L; McMahon, Robert J; Jouni, Zeina E; Ferruzzi, Mario G

    2014-10-01

    Clinical evidence suggests that the bioavailability of lutein is lower from infant formula than from human milk. The purpose of this study was to assess characteristics of human milk and lutein-fortified infant formula that may impact carotenoid delivery. Carotenoid bioaccessibility and intestinal absorption were modeled by in vitro digestion coupled with Caco-2 human intestinal cell culture. Twelve human milk samples were assessed from 1-6 months postpartum, and 10 lutein-fortified infant formula samples from three lutein sources in both ready-to-use and reconstituted powder forms. The relative bioaccessibility of lutein was not different (p > 0.05) between human milk (29 ± 2%) and infant formula (36 ± 4%). However, lutein delivery was 4.5 times greater from human milk than infant formula when including Caco-2 accumulation efficiency. Caco-2 accumulation of lutein was increasingly efficient with decreasing concentration of lutein from milk. Carotenoid bioaccessibility and Caco-2 accumulation were not affected by lactation stage, total lipid content, lutein source, or form of infant formula (powder vs. liquid). These data suggest that the bioavailability of carotenoids is greater from human milk than infant formula primarily due to intestinal absorptive processes, and that absorption of lutein is potentiated by factors from human milk especially at low lutein concentration. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The Collaborative Assessment and Management of Suicidality (CAMS): An Evolving Evidence-Based Clinical Approach to Suicidal Risk

    ERIC Educational Resources Information Center

    Jobes, David A.

    2012-01-01

    The Collaborative Assessment and Management of Suicidality (CAMS) is an evidence-based clinical intervention that has significantly evolved over 25 years of clinical research. CAMS is best understood as a therapeutic framework that emphasizes a unique collaborative assessment and treatment planning process between the suicidal patient and…

  20. Evidence of common and separate eye and hand accumulators underlying flexible eye-hand coordination

    PubMed Central

    Jana, Sumitash; Gopal, Atul

    2016-01-01

    Eye and hand movements are initiated by anatomically separate regions in the brain, and yet these movements can be flexibly coupled and decoupled, depending on the need. The computational architecture that enables this flexible coupling of independent effectors is not understood. Here, we studied the computational architecture that enables flexible eye-hand coordination using a drift diffusion framework, which predicts that the variability of the reaction time (RT) distribution scales with its mean. We show that a common stochastic accumulator to threshold, followed by a noisy effector-dependent delay, explains eye-hand RT distributions and their correlation in a visual search task that required decision-making, while an interactive eye and hand accumulator model did not. In contrast, in an eye-hand dual task, an interactive model better predicted the observed correlations and RT distributions than a common accumulator model. Notably, these two models could only be distinguished on the basis of the variability and not the means of the predicted RT distributions. Additionally, signatures of separate initiation signals were also observed in a small fraction of trials in the visual search task, implying that these distinct computational architectures were not a manifestation of the task design per se. Taken together, our results suggest two unique computational architectures for eye-hand coordination, with task context biasing the brain toward instantiating one of the two architectures. NEW & NOTEWORTHY Previous studies on eye-hand coordination have considered mainly the means of eye and hand reaction time (RT) distributions. Here, we leverage the approximately linear relationship between the mean and standard deviation of RT distributions, as predicted by the drift-diffusion model, to propose the existence of two distinct computational architectures underlying coordinated eye-hand movements. These architectures, for the first time, provide a computational basis for

  1. Evidence-based clinical practice guidelines for liver cirrhosis 2015.

    PubMed

    Fukui, Hiroshi; Saito, Hidetsugu; Ueno, Yoshiyuki; Uto, Hirofumi; Obara, Katsutoshi; Sakaida, Isao; Shibuya, Akitaka; Seike, Masataka; Nagoshi, Sumiko; Segawa, Makoto; Tsubouchi, Hirohito; Moriwaki, Hisataka; Kato, Akinobu; Hashimoto, Etsuko; Michitaka, Kojiro; Murawaki, Toshikazu; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-07-01

    The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for

  2. The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications.

    PubMed

    Stugiewicz, Magdalena; Tkaczyszyn, Michał; Kasztura, Monika; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

    2016-07-01

    Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  3. Conifer ovulate cones accumulate pollen principally by simple impaction.

    PubMed

    Cresswell, James E; Henning, Kevin; Pennel, Christophe; Lahoubi, Mohamed; Patrick, Michael A; Young, Phillipe G; Tabor, Gavin R

    2007-11-13

    In many pine species (Family Pinaceae), ovulate cones structurally resemble a turbine, which has been widely interpreted as an adaptation for improving pollination by producing complex aerodynamic effects. We tested the turbine interpretation by quantifying patterns of pollen accumulation on ovulate cones in a wind tunnel and by using simulation models based on computational fluid dynamics. We used computer-aided design and computed tomography to create computational fluid dynamics model cones. We studied three species: Pinus radiata, Pinus sylvestris, and Cedrus libani. Irrespective of the approach or species studied, we found no evidence that turbine-like aerodynamics made a significant contribution to pollen accumulation, which instead occurred primarily by simple impaction. Consequently, we suggest alternative adaptive interpretations for the structure of ovulate cones.

  4. Conifer ovulate cones accumulate pollen principally by simple impaction

    PubMed Central

    Cresswell, James E.; Henning, Kevin; Pennel, Christophe; Lahoubi, Mohamed; Patrick, Michael A.; Young, Phillipe G.; Tabor, Gavin R.

    2007-01-01

    In many pine species (Family Pinaceae), ovulate cones structurally resemble a turbine, which has been widely interpreted as an adaptation for improving pollination by producing complex aerodynamic effects. We tested the turbine interpretation by quantifying patterns of pollen accumulation on ovulate cones in a wind tunnel and by using simulation models based on computational fluid dynamics. We used computer-aided design and computed tomography to create computational fluid dynamics model cones. We studied three species: Pinus radiata, Pinus sylvestris, and Cedrus libani. Irrespective of the approach or species studied, we found no evidence that turbine-like aerodynamics made a significant contribution to pollen accumulation, which instead occurred primarily by simple impaction. Consequently, we suggest alternative adaptive interpretations for the structure of ovulate cones. PMID:17986613

  5. Evidence-based medicine: medical librarians providing evidence at the point of care.

    PubMed

    Yaeger, Lauren H; Kelly, Betsy

    2014-01-01

    Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. .. by best available external clinical evidence we mean clinically relevant research.' Health care reform authorized by the Affordable Care Act is based on the belief that evidence-based practice (EBP) generates cost savings due to the delivery of more effective care.2 Medical librarians, skilled in identifying appropriate resources and working with multiple complex interfaces, can support clinicians' efforts to practice evidence based medicine by providing time and expertise in articulating the clinical question and identifying the best evidence.

  6. The Physics of Decision Making:. Stochastic Differential Equations as Models for Neural Dynamics and Evidence Accumulation in Cortical Circuits

    NASA Astrophysics Data System (ADS)

    Holmes, Philip; Eckhoff, Philip; Wong-Lin, K. F.; Bogacz, Rafal; Zacksenhouse, Miriam; Cohen, Jonathan D.

    2010-03-01

    We describe how drift-diffusion (DD) processes - systems familiar in physics - can be used to model evidence accumulation and decision-making in two-alternative, forced choice tasks. We sketch the derivation of these stochastic differential equations from biophysically-detailed models of spiking neurons. DD processes are also continuum limits of the sequential probability ratio test and are therefore optimal in the sense that they deliver decisions of specified accuracy in the shortest possible time. This leaves open the critical balance of accuracy and speed. Using the DD model, we derive a speed-accuracy tradeoff that optimizes reward rate for a simple perceptual decision task, compare human performance with this benchmark, and discuss possible reasons for prevalent sub-optimality, focussing on the question of uncertain estimates of key parameters. We present an alternative theory of robust decisions that allows for uncertainty, and show that its predictions provide better fits to experimental data than a more prevalent account that emphasises a commitment to accuracy. The article illustrates how mathematical models can illuminate the neural basis of cognitive processes.

  7. Types, Mechanisms, and Clinical Cardiovascular Consequences

    PubMed Central

    Javaheri, Shahrokh; Barbe, Ferran; Campos-Rodriguez, Francisco; Dempsey, Jerome A.; Khayat, Rami; Javaheri, Sogol; Malhotra, Atul; Martinez-Garcia, Miguel A.; Mehra, Reena; Pack, Allan I.; Polotsky, Vsevolod Y.; Redline, Susan; Somers, Virend K.

    2017-01-01

    Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke. Several discoveries in the pathogenesis, along with developments in the treatment of sleep apnea, have accumulated in recent years. In this review, we discuss the mechanisms of sleep apnea, the evidence that addresses the links between sleep apnea and cardiovascular disease, and research that has addressed the effect of sleep apnea treatment on cardiovascular disease and clinical endpoints. Finally, we review the recent development in sleep apnea treatment options, with special consideration of treating patients with heart disease. Future directions for selective areas are suggested. PMID:28209226

  8. Azelaic Acid: Evidence-based Update on Mechanism of Action and Clinical Application.

    PubMed

    Schulte, Brian C; Wu, Wesley; Rosen, Ted

    2015-09-01

    Azelaic acid is a complex molecule with many diverse activities. The latter include anti-infective and anti-inflammatory action. The agent also inhibits follicular keratinization and epidermal melanogenesis. Due to the wide variety of biological activities, azelaic acid has been utilized as a management tool in a broad spectrum of disease states and cutaneous disorders. This paper reviews the clinical utility of azelaic acid, noting the quality of the evidence supporting each potential use.

  9. Immunomodulators in SLE: Clinical evidence and immunologic actions.

    PubMed

    Durcan, L; Petri, M

    2016-11-01

    Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease. Current treatment strategies rely heavily on corticosteroids, which are in turn responsible for a significant burden of morbidity, and immunosuppressives which are limited by suboptimal efficacy, increased infections and malignancies. There are significant deficiencies in our immunosuppressive armamentarium, making immunomodulatory therapies crucial, offering the opportunity to prevent disease flare and the subsequent accrual of damage. Currently available immunomodulators include prasterone (synthetic dehydroeipandrosterone), vitamin D, hydroxychloroquine and belimumab. These therapies, acting via numerous cellular and cytokine pathways, have been shown to modify the aberrant immune responses associated with SLE without overt immunosuppression. Vitamin D is important in SLE and supplementation appears to have a positive impact on disease activity particularly proteinuria. Belimumab has specific immunomodulatory properties and is an effective therapy in those with specific serological and clinical characteristics predictive of response. Hydroxychloroquine is a crucial background medication in SLE with actions in many molecular pathways. It has disease specific effects in reducing flare, treating cutaneous disease and inflammatory arthralgias in addition to other effects such as reduced thrombosis, increased longevity, improved lipids, better glycemic control and blood pressure. Dehydroeipandrosterone is also an immunomodulator in SLE which can have positive effects on disease activity and has bone protective properties. This review outlines the immunologic actions of these drugs and the clinical evidence supporting their use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

    PubMed

    Federici, Silvia; Sormani, Maria Pia; Ozen, Seza; Lachmann, Helen J; Amaryan, Gayane; Woo, Patricia; Koné-Paut, Isabelle; Dewarrat, Natacha; Cantarini, Luca; Insalaco, Antonella; Uziel, Yosef; Rigante, Donato; Quartier, Pierre; Demirkaya, Erkan; Herlin, Troels; Meini, Antonella; Fabio, Giovanna; Kallinich, Tilmann; Martino, Silvana; Butbul, Aviel Yonatan; Olivieri, Alma; Kuemmerle-Deschner, Jasmin; Neven, Benedicte; Simon, Anna; Ozdogan, Huri; Touitou, Isabelle; Frenkel, Joost; Hofer, Michael; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco

    2015-05-01

    The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Maximum likelihood decoding analysis of Accumulate-Repeat-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    Repeat-Accumulate (RA) codes are the simplest turbo-like codes that achieve good performance. However, they cannot compete with Turbo codes or low-density parity check codes (LDPC) as far as performance is concerned. The Accumulate Repeat Accumulate (ARA) codes, as a subclass of LDPC codes, are obtained by adding a pre-coder in front of RA codes with puncturing where an accumulator is chosen as a precoder. These codes not only are very simple, but also achieve excellent performance with iterative decoding. In this paper, the performance of these codes with (ML) decoding are analyzed and compared to random codes by very tight bounds. The weight distribution of some simple ARA codes is obtained, and through existing tightest bounds we have shown the ML SNR threshold of ARA codes approaches very closely to the performance of random codes. We have shown that the use of precoder improves the SNR threshold but interleaving gain remains unchanged with respect to RA code with puncturing.

  12. The effectiveness of toolkits as knowledge translation strategies for integrating evidence into clinical care: a systematic review

    PubMed Central

    Yamada, Janet; Shorkey, Allyson; Barwick, Melanie; Widger, Kimberley; Stevens, Bonnie J

    2015-01-01

    Objectives The aim of this systematic review was to evaluate the effectiveness of toolkits as a knowledge translation (KT) strategy for facilitating the implementation of evidence into clinical care. Toolkits include multiple resources for educating and/or facilitating behaviour change. Design Systematic review of the literature on toolkits. Methods A search was conducted on MEDLINE, EMBASE, PsycINFO and CINAHL. Studies were included if they evaluated the effectiveness of a toolkit to support the integration of evidence into clinical care, and if the KT goal(s) of the study were to inform, share knowledge, build awareness, change practice, change behaviour, and/or clinical outcomes in healthcare settings, inform policy, or to commercialise an innovation. Screening of studies, assessment of methodological quality and data extraction for the included studies were conducted by at least two reviewers. Results 39 relevant studies were included for full review; 8 were rated as moderate to strong methodologically with clinical outcomes that could be somewhat attributed to the toolkit. Three of the eight studies evaluated the toolkit as a single KT intervention, while five embedded the toolkit into a multistrategy intervention. Six of the eight toolkits were partially or mostly effective in changing clinical outcomes and six studies reported on implementation outcomes. The types of resources embedded within toolkits varied but included predominantly educational materials. Conclusions Future toolkits should be informed by high-quality evidence and theory, and should be evaluated using rigorous study designs to explain the factors underlying their effectiveness and successful implementation. PMID:25869686

  13. Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop.

    PubMed

    Lenz, B; Braendli-Baiocco, A; Engelhardt, J; Fant, P; Fischer, H; Francke, S; Fukuda, R; Gröters, S; Harada, T; Harleman, H; Kaufmann, W; Kustermann, S; Nolte, T; Palazzi, X; Pohlmeyer-Esch, G; Popp, A; Romeike, A; Schulte, A; Lima, B Silva; Tomlinson, L; Willard, J; Wood, C E; Yoshida, M

    2018-02-01

    Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.

  14. Electronic Clinic Journaling: The Use of Weblogs to Support Evidence-Based Practice in Doctor of Audiology Students

    ERIC Educational Resources Information Center

    Neldon, Gayle B.

    2009-01-01

    Evidence-based practice (EBP) is a strategy for the provision of high quality health care. The use of journals to document clinical experiences and reflection has been used in speech-language pathology as well as nursing and psychology. This study uses qualitative analysis to study what AuD students learn about evidence-based practice from writing…

  15. Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany.

    PubMed

    Isbary, Georg; Staab, Thomas R; Amelung, Volker E; Dintsios, Charalabos-Markos; Iking-Konert, Christof; Nesurini, Sonja Mariotti; Walter, Miriam; Ruof, Jörg

    2018-06-01

    In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects. To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA). For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications. Eleven of 21 benefit assessments included crossover trials. Significant intergroup differences (P < 0.05) in overall survival (OS) were noted in 7 of 11 trials with and 7 of 10 without crossover. For 6 of 11 medicines with crossover, these were demonstrated before crossover. Treatment effects generally worsened with increasing proportions of crossover. The EMA requested additional data more frequently if crossover was performed, particularly if no OS data were available before crossover. The G-BA granted a considerable benefit to 73% of medicines with crossover and 40% of those without. Evidence levels were intermediate for 50% and 75%, respectively. None of the medicines received the highest evidence level. In G-BA appraisals, oncology medicines with crossover received better additional benefit ratings, but were assigned lower evidence levels, than those without. The five medicines with crossover after progression were assigned lower evidence levels than the six medicines with crossover after demonstration of superior OS, indicating that the way in which crossover is implemented may be one factor influencing the assignment of evidence levels by the G-BA. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  16. Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review.

    PubMed

    Roffi, Alice; Di Matteo, Berardo; Krishnakumar, Gopal Shankar; Kon, Elizaveta; Filardo, Giuseppe

    2017-02-01

    The treatment of large bone defects represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have also been used to further improve bone healing. Among these, platelet-rich plasma (PRP) is the most exploited strategy. The aim of the present study was to systematically review the available literature to identify: 1) preclinical in-vivo results supporting the rational of PRP use for bone healing; 2) evidence from the clinical practice on the actual clinical benefit of PRP for the treatment of fractures and complications such as delayed unions and non-unions. A systematic review of the literature was performed on the application of PRP in bone healing, using the following inclusion criteria: pre-clinical and clinical reports of any level of evidence, written in English language, published in the last 20 years (1996-2016), on the use of PRP to stimulate long-bone defect treatment, with focus on fracture and delayed/non-unions healing. The search in the Pubmed database identified 64 articles eligible for inclusion: 45 were preclinical in-vivo studies and 19 were clinical studies. Despite the fact that the overall pre-clinical results seem to support the benefit of PRP in 91.1 % of the studies, a more in depth analysis underlined a lower success rate, with a positive outcome of 84.4 % in terms of histological analysis, and even lower values considering radiological and biomechanical results (75.0 % and 72.7 % positive outcome respectively). This was also mirrored in the clinical literature, where the real benefit of PRP use to treat fractures and non-unions is still under debate. Overall, the available literature presents major limitations in terms of low quality and extreme heterogeneity, which hamper the possibility to optimize PRP treatment and translate it into a real clinical benefit despite positive preclinical findings on its biological potential to favour bone healing.

  17. Mental exercises for cognitive function: clinical evidence.

    PubMed

    Kawashima, Ryuta

    2013-01-01

    The purpose of this study was to examine the beneficial effects of a new cognitive intervention program designed for the care and prevention of dementia, namely Learning Therapy. The training program used systematized basic problems in arithmetic and Japanese language as training tasks. In study 1, 16 individuals in the experimental group and 16 in the control group were recruited from a nursing home. In both groups, all individuals were clinically diagnosed with senile dementia of the Alzheimer type. In study 2, we performed a single-blind, randomized controlled trial in our cognitive intervention program of 124 community-dwelling seniors. In both studies, the daily training program using reading and arithmetic tasks was carried out approximately 5 days a week, for 15 to 20 minutes a day in the intervention groups. Neuropsychological measures were determined simultaneously in the groups both prior to and after six months of the intervention. The results of our investigations indicate that our cognitive intervention using reading and arithmetic problems demonstrated a transfer effect and they provide convincing evidence that cognitive training maintains and improves the cognitive functions of dementia patients and healthy seniors.

  18. Association of Lipid Accumulation Product with Cardio-Metabolic Risk Factors in Postmenopausal Women.

    PubMed

    Namazi Shabestari, Alireza; Asadi, Mojgan; Jouyandeh, Zahra; Qorbani, Mostafa; Kelishadi, Roya

    2016-06-01

    The lipid accumulation product is a novel, safe and inexpensive index of central lipid over accumulation based on waist circumference and fasting concentration of circulating triglycerides. This study was designed to investigate the ability of lipid accumulation product to predict Cardio-metabolic risk factors in postmenopausal women. In this Cross-sectional study, 264 postmenopausal women by using convenience sampling method were selected from menopause clinic in Tehran. Cardio-metabolic risk factors were measured, and lipid accumulation product (waist-58×triglycerides [nmol/L]) was calculated. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was estimated by ROC (Receiver-operating characteristic) curve analysis. Metabolic syndrome was diagnosed in 41.2% of subjects. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was 47.63 (sensitivity:75%; specificity:77.9%). High lipid accumulation product increases risk of all Cardio-metabolic risk factors except overweight, high Total Cholesterol, high Low Density Lipoprotein Cholesterol and high Fasting Blood Sugar in postmenopausal women. Our findings show that lipid accumulation product is associated with metabolic syndrome and some Cardio-metabolic risk factors Also lipid accumulation product may have been a useful tool for predicting cardiovascular disease and metabolic syndrome risk in postmenopausal women.

  19. Retrieving clinical evidence: a comparison of PubMed and Google Scholar for quick clinical searches.

    PubMed

    Shariff, Salimah Z; Bejaimal, Shayna Ad; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

    2013-08-15

    Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. To compare the performance of searches in PubMed and Google Scholar. We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

  20. The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

    PubMed Central

    Makrigiannakis, Antonis; Vrekoussis, Thomas; Zoumakis, Emmanouel; Kalantaridou, Sophia N.; Jeschke, Udo

    2017-01-01

    Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. PMID:28629172

  1. Clinically assisted hydration and the Liverpool Care Pathway: Catholic ethics and clinical evidence.

    PubMed

    Nowarska, Anna

    2015-08-01

    The Liverpool Care Pathway for the Dying Patient (LCP), a framework introduced for providing comfortable care at the last stage of life, has recently become highly contentious. Among the most serious allegations levelled against it, has been that the LCP may be used as a covert form of euthanasia by withdrawal of clinically assisted hydration (CAH). This concern has been raised, in particular by a number of Catholic medical professionals, who have asserted that the LCP is incompatible with Catholic ethics. This paper examines the key Catholic ethical principles relevant to treatment and care towards the end of life (the sanctity/inviolability of life principle, the distinction between ordinary and extraordinary means). Relevant current clinical evidence regarding CAH in relation to terminal thirst, dehydration, prolongation of life and possible negative impacts on the dying is also scrutinised. It is argued that for some patients at the very end of life it may be permissible and even desirable to withhold or withdraw it. Thus, as administration of CAH may become extraordinary, forgoing it in some situations is fully compatible with Catholic ethics. The article therefore concludes that the stance of the LCP in respect of provision of CAH is fully in alignment with Catholic teaching. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Counseling in the clinical setting to prevent unintended pregnancy: an evidence-based research agenda.

    PubMed

    Moos, Merry K; Bartholomew, Neva E; Lohr, Kathleen N

    2003-02-01

    Unintended pregnancies account for about half of all pregnancies in the United States and, in 1995, numbered nearly 3 million pregnancies. They pose appreciable medical, emotional, social and financial costs on women, their families and society. The US is not attaining national goals to decrease unintended pregnancies, and little is known about effective means for reducing unintended pregnancy rates in adults or adolescents.To examine the evidence about the effectiveness, benefits and harms of counseling in a clinical setting to prevent unintended pregnancy in adults and adolescents and to use the evidence to propose a research agenda.We identified English-language articles from comprehensive searches of the MEDLINE, CINAHL, PsychLit and other databases from 1985 through May 2000; the main clinical search terms included pregnancy (mistimed, unintended, unplanned, unwanted), family planning, contraceptive behavior, counseling, sex counseling, and knowledge, attitudes and behavior. We also used published systematic reviews, hand searching of relevant articles, the second Guide to Clinical Preventive Services and extensive peer review to identify important articles not otherwise found and to assure completeness. Of 673 abstracts examined, we retained 354 for full article review; of these, we used 74 for the systematic evidence review and abstracted data from 13 articles for evidence tables. Four studies addressed the effectiveness of counseling in a clinical setting in changing knowledge, skills and attitudes about contraception and pregnancy; all had poor internal validity and generalizability and collectively did not provide definitive guidance about effective counseling strategies. Nine studies (three in teenage populations) addressed the relationship of knowledge on contraceptive use and adherence. Knowledge of correct contraceptive methods may be positively associated with appropriate use, but reservations about the method itself, partner support of the method

  3. Approved Clinical Instructors' Perspectives on Implementation Strategies in Evidence-Based Practice for Athletic Training Students

    PubMed Central

    Hankemeier, Dorice A.; Van Lunen, Bonnie L.

    2011-01-01

    Context: Understanding implementation strategies of Approved Clinical Instructors (ACIs) who use evidence-based practice (EBP) in clinical instruction will help promote the use of EBP in clinical practice. Objective: To examine the perspectives and experiences of ACIs using EBP concepts in undergraduate athletic training education programs to determine the importance of using these concepts in clinical practice, clinical EBP implementation strategies for students, and challenges of implementing EBP into clinical practice while mentoring and teaching their students. Design: Qualitative study. Setting: Telephone interviews. Patients or Other Participants: Sixteen ACIs (11 men, 5 women; experience as a certified athletic trainer = 10 ± 4.7 years, experience as an ACI = 6.8 ± 3.9 years) were interviewed. Data Collection and Analysis: We interviewed each participant by telephone. Interview transcripts were analyzed and coded for common themes and subthemes regarding implementation strategies. Established themes were triangulated through peer review and member checking to verify the data. Results: The ACIs identified EBP implementation as important for validation of the profession, changing paradigm shift, improving patient care, and improving student educational experiences. They promoted 3 methods of implementing EBP concepts with their students: self-discovery, promoting critical thinking, and sharing information. They assisted students with the steps of EBP and often faced challenges in implementation of the first 3 steps of EBP: defining a clinical question, literature searching, and literature appraisal. Finally, ACIs indicated that modeling the behavior of making clinical decisions based on evidence was the best way to encourage students to continue using EBP. Conclusions: Athletic training education program directors should encourage and recommend specific techniques for EBP implementation in the clinical setting. The ACIs believed that role modeling is a

  4. Local accumulation times for spatial difference in morphogen concentration

    NASA Astrophysics Data System (ADS)

    Wen, Xiaoqing; Yin, Hongwei

    During development of multicellular organisms, spatial patterns of cells and tissue organizations rely on the action of morphogens, which are signaling molecules and act as dose-dependent regulators of gene expression and cellular differentiation. Since some experimental evidences have indicated that the spatial difference in morphogen concentration regulates cellular proliferation rather than this concentration profile in developing tissues, we propose spatially discrete models to describe this difference for a synthesis-diffusion-degradation process of morphogen in infinite and finite development fields, respectively. For both of models, we respectively derive analytical expressions of local accumulation times, which are required to form the steady state of the spatial difference in morphogen concentration. Our results show that the local accumulation times for the spatial difference in morphogen concentrations are different from the ones for morphogen concentration profiles.

  5. Lumiracoxib: the evidence of its clinical impact on the treatment of osteoarthritis

    PubMed Central

    Profit, Louise; Chrisp, Paul

    2007-01-01

    Introduction: The symptoms of osteoarthritis (OA) include joint pain, stiffness, and a reduced ability to perform normal daily activities, which result in decreased quality of life. There is currently no known cure or means of preventing the progression of joint damage due to OA. Therefore, treatment focuses on the control of symptoms, including the use of various agents [including nonselective and selective nonsteroidal antiinflammatory drugs (NSAIDs)] to provide pain relief and reduce inflammation. Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of OA. Aims: To review the evidence for the treatment of OA with lumiracoxib. Evidence review: There is evidence that lumiracoxib reduces the pain and stiffness associated with OA, and is as effective as nonselective NSAIDs, and the COX-2 inhibitor celecoxib. There is some evidence that lumiracoxib treatment results in a lower incidence of upper gastrointestinal (GI) ulcer complications compared with nonselective NSAIDs. However, evidence suggests that there is no GI benefit in patients receiving concomitant aspirin medication. With the exception of GI ulcers, the evidence indicates that lumiracoxib has a tolerability profile similar to nonselective NSAIDs: low risk of cardiovascular (CV) events and a low incidence of edema. Changes in liver function occur in some patients, largely at doses >100 mg. The cost effectiveness of lumiracoxib compared with nonselective NSAIDs remains to be determined. Clinical value: Lumiracoxib is an alternative treatment option for OA which provides effective pain relief without the GI complications associated with nonselective NSAIDs, and with a low risk of CV events. Lumiracoxib is contraindicated in patients with current, previous, or at risk of, hepatic impairment. PMID:21221181

  6. Clinical practice guidelines on the evidence-based use of integrative therapies during and following breast cancer treatment

    PubMed Central

    Greenlee, Heather; DuPont-Reyes, Melissa J.; Balneaves, Lynda G.; Carlson, Linda E.; Cohen, Misha R.; Deng, Gary; Johnson, Jillian A.; Mumber, Matthew; Seely, Dugald; Zick, Suzanna; Boyce, Lindsay; Tripathy, Debu

    2018-01-01

    Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. PMID:28436999

  7. Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials.

    PubMed

    Figueroa, Xavier A; Wright, James K

    2016-09-27

    First, to demonstrate that B-level evidence exists for the use of hyperbaric oxygen therapy (HBOT) as an effective treatment in mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS). Second, to alert readers and researchers that currently used pressurized air controls (≥21% O2, >1.0 ATA) are therapeutically active and cannot be utilized as sham controls without further validation. Review of published, peer-reviewed articles of HBOT prospective and controlled clinical trials of mTBI/PPCS symptoms. Published results demonstrate that HBOT is effective in the treatment of mTBI/PPCS symptoms. Doses of oxygen that are applied at ≥21% O2 and at pressures of >1.0 ATA produce improvements from baseline measures. Some of the recently published clinical trials are mischaracterized as sham-controlled clinical trials (i.e., sham = 21% O2/1.2-1.3 ATA), but are best characterized as dose-varying (variation in oxygen concentration, pressure applied, or both) clinical trials. Hyperbaric oxygen and hyperbaric air have demonstrated therapeutic effects on mTBI/PPCS symptoms and can alleviate posttraumatic stress disorder symptoms secondary to a brain injury in 5 out of 5 peer-reviewed clinical trials. The current use of pressurized air (1.2-1.3 ATA) as a placebo or sham in clinical trials biases the results due to biological activity that favors healing. © 2016 American Academy of Neurology.

  8. Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment*

    PubMed Central

    da Silva, Luiz Vicente Ribeiro Ferreira; Ferreira, Flavia de Aguiar; Reis, Francisco José Caldeira; de Britto, Murilo Carlos Amorim; Levy, Carlos Emilio; Clark, Otavio; Ribeiro, José Dirceu

    2013-01-01

    Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO–an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group. PMID:24068273

  9. A Model for Evidence Accumulation in the Lexical Decision Task

    ERIC Educational Resources Information Center

    Wagenmakers, Eric-Jan; Steyvers, Mark; Raaijmakers, Jeroen G. W.; Shiffrin, Richard M.; van Rijn, Hedderik; Zeelenberg, Rene

    2004-01-01

    We present a new model for lexical decision, REM-LD, that is based on REM theory (e.g., Shiffrin & Steyvers, 1997). REM-LD uses a principled (i.e., Bayes' rule) decision process that simultaneously considers the diagnosticity of the evidence for the 'WORD' response and the 'NONWORD' response. The model calculates the odds ratio that the presented…

  10. How are evidence and knowledge used in orthopaedic decision-making? Three comparative case studies of different approaches to implementation of clinical guidance in practice.

    PubMed

    Grove, Amy; Clarke, Aileen; Currie, Graeme

    2018-05-31

    The uptake and use of clinical guidelines is often insufficient to change clinical behaviour and reduce variation in practice. As a consequence of diverse organisational contexts, the simple provision of guidelines cannot ensure fidelity or guarantee their use when making decisions. Implementation research in surgery has focused on understanding what evidence exists for clinical practice decisions but limits understanding to the technical, educational and accessibility issues. This research aims to identify where, when and how evidence and knowledge are used in orthopaedic decision-making and how variation in these factors contributes to different approaches to implementation of clinical guidance in practice. We used in-depth case studies to examine guideline implementation in real-life surgical practice. We conducted comparative case studies in three English National Health Service hospitals over a 12-month period. Each in-depth case study consisted of a mix of qualitative methods including interviews, observations and document analysis. Data included field notes from observations of day-to-day practice, 64 interviews with NHS surgeons and staff and the collection of 121 supplementary documents. Case studies identified 17 sources of knowledge and evidence which influenced clinical decisions in elective orthopaedic surgery. A comparative analysis across cases revealed that each hospital had distinct approaches to decision-making. Decision-making is described as occurring as a result of how 17 types of knowledge and evidence were privileged and of how they interacted and changed in context. Guideline implementation was contingent and mediated through four distinct contextual levels. Implementation could be assessed for individual surgeons, groups of surgeons or the organisation as a whole, but it could also differ between these levels. Differences in how evidence and knowledge were used contributed to variations in practice from guidelines. A range of complex and

  11. Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

    PubMed Central

    Brocklebank, Vicky

    2017-01-01

    Abstract Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs. PMID:28980670

  12. Streptococcus mutans Adherence: Presumptive Evidence for Protein-Mediated Attachment Followed by Glucan-Dependent Cellular Accumulation

    PubMed Central

    Staat, Robert H.; Langley, Sharon D.; Doyle, R. J.

    1980-01-01

    Adherence of Streptococcus mutans to smooth surfaces has been attributed to the production of sucrose-derived d-glucans. However, several studies indicate that the bacterium will adhere in the absence of sucrose. The present data confirmed that S. mutans adherence to saliva-coated hydroxyapatite beads in the absence of sucrose is described by the Langmuir equation. The nature of the sucrose-independent adherence was studied with the Persea americana agglutinin as a selective adherence inhibitor. Pretreatment of the bacterium with P. americana agglutinin caused a 10-fold reduction in adherence, and the inhibition was not reversed with the addition of sucrose. Pretreatment of S. mutans with proteases also reduced adherence, regardless of the sucrose content, whereas periodate oxidation and glucanohydrolase treatment of the bacteria reduced sucrose-mediated adherence to the levels found for sucrose-independent adherence. The P. americana agglutinin, glucanohydrolase, and pepsin pretreatment of the cells did not eliminate sucrose-induced agglutination. Scanning electron microscopy showed that short streptococcal chains were bound to saliva-coated hydroxyapatite crystals in the sucrose-independent system, whereas the presence of sucrose caused larger bacterial clumps to be found. A two-reaction model of S. mutans adherence was developed from these data. It is proposed that one reaction is attachment to the tooth pellicle which is mediated by cell-surface proteins rather than glucans or teichoic acids. The other reaction is cellular accumulation mediated by sucrose-derived d-glucans and cell surface lectins. A series of sequential adherence experiments with P. americana agglutinin as a selective inhibitor provided presumptive evidence for the validity of our model of S. mutans adherence. Images Fig. 1 PMID:7380545

  13. Analytical evidence of heterogeneous lead accumulation in the hypothalamic defence area and nucleus tractus solitarius.

    PubMed

    Guimarães, D; Santos, J P; Carvalho, M L; Diniz, M S; House, B; Miller, V M

    2014-09-01

    Lead is a potent toxicant associated with adverse cardiovascular effects and hypertension in children. Yet, few studies have determined if autonomic dysfunction associated with lead exposure involves brain regions which regulate autonomic responses. Central autonomic nuclei such as the nucleus tractus solitarius (NTS) and hypothalamic defence area (HDA) may be particularly sensitive to lead infiltration because they are adjacent to ventricles and areas with semi-permeable blood-brain-barriers. To understand if autonomic nuclei are sensitive to lead accumulation Wistar rats were exposed to lead from the gestational period and lead levels were quantified in brain regions that regulate arterial pressure: the NTS and the HDA. Energy dispersive X-ray fluorescence (EDXRF) was used to quantify total brain lead levels and revealed no differences between exposed and control tissues; measured values were close to the detection limit (2μg/g). Electrothermal atomic absorption spectrometry (ETAAS) was also used, which has a greater sensitivity, to quantify lead. There was ∼2.1μg/g lead in the NTS and ∼3.1μg/g lead in the HDA of exposed rats, and no lead in the control rats. There were greater lead levels in the HDA (∼50%) as compared with the NTS. Pathology studies revealed more prominent lead granules in the HDA as compared with the NTS. Increased microglia and astrocyte activation was also noted in the NTS of lead exposed rats as compared with the HDA. Regional differences in neuro-inflammatory responses likely contribute to heterogeneous lead accumulation, with enhanced clearance of lead in the NTS. Future studies will resolve the mechanisms underpinning tissue-specific lead accumulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Regional Greenland accumulation variability from Operation IceBridge airborne accumulation radar

    NASA Astrophysics Data System (ADS)

    Lewis, Gabriel; Osterberg, Erich; Hawley, Robert; Whitmore, Brian; Marshall, Hans Peter; Box, Jason

    2017-03-01

    The mass balance of the Greenland Ice Sheet (GrIS) in a warming climate is of critical interest to scientists and the general public in the context of future sea-level rise. An improved understanding of temporal and spatial variability of snow accumulation will reduce uncertainties in GrIS mass balance models and improve projections of Greenland's contribution to sea-level rise, currently estimated at 0.089 ± 0.03 m by 2100. Here we analyze 25 NASA Operation IceBridge accumulation radar flights totaling > 17 700 km from 2013 to 2014 to determine snow accumulation in the GrIS dry snow and percolation zones over the past 100-300 years. IceBridge accumulation rates are calculated and used to validate accumulation rates from three regional climate models. Averaged over all 25 flights, the RMS difference between the models and IceBridge accumulation is between 0.023 ± 0.019 and 0.043 ± 0.029 m w.e. a-1, although each model shows significantly larger differences from IceBridge accumulation on a regional basis. In the southeast region, for example, the Modèle Atmosphérique Régional (MARv3.5.2) overestimates by an average of 20.89 ± 6.75 % across the drainage basin. Our results indicate that these regional differences between model and IceBridge accumulation are large enough to significantly alter GrIS surface mass balance estimates. Empirical orthogonal function analysis suggests that the first two principal components account for 33 and 19 % of the variance, and correlate with the Atlantic Multidecadal Oscillation (AMO) and wintertime North Atlantic Oscillation (NAO), respectively. Regions that disagree strongest with climate models are those in which we have the fewest IceBridge data points, requiring additional in situ measurements to verify model uncertainties.

  15. Evaluating online continuing medical education seminars: evidence for improving clinical practices.

    PubMed

    Weston, Christine M; Sciamanna, Christopher N; Nash, David B

    2008-01-01

    The purpose of this study was to evaluate the potential for online continuing medical education (CME) seminars to improve quality of care. Primary care physicians (113) participated in a randomized controlled trial to evaluate an online CME series. Physicians were randomized to view either a seminar about type 2 diabetes or a seminar about systolic heart failure. Following the seminar, physicians were presented with 4 clinical vignettes and asked to describe what tests, treatments, counseling, or referrals they would recommend. Physicians who viewed the seminars were significantly more likely to recommend guideline-consistent care to patients in the vignettes. For example, physicians who viewed the diabetes seminar were significantly more likely to order an eye exam for diabetes patients (63%) compared with physicians in the control group (27%). For some guidelines there were no group differences. These results provide early evidence of the effectiveness of online CME programs to improve physician clinical practice.

  16. Differing levels of clinical evidence: exploring communication challenges in shared decision making. Introduction.

    PubMed

    Smith, Quentin W; Street, Richard L; Volk, Robert J; Fordis, Michael

    2013-02-01

    The near ubiquitous access to information is transforming the roles and relationships among clinical professionals, patients, and their care givers in nearly all aspects of healthcare. Informed patients engage their physicians in conversations about their conditions, options and the tradeoffs among diagnostic and therapeutic benefits and harms. The processes of care today increasingly and explicitly integrate exploration of patient values and preferences as patients and clinicians jointly engage in reaching decisions about care. The informed patient of today who can understand and use scientific information can participate as an equal partner with her clinician. Others with beliefs or educational, cultural, or literacy backgrounds that pose challenges to comprehending and applying evidence may face disenfranchisement. These barriers are significant enough, even in the face of certainty of evidence, that clinicians and investigators have given much thought to how best to engage all patients in decision making. However, barriers remain, as most decision making must occur in settings where uncertainty, if not considerable uncertainty, accompanies any statement of what we know. In September 2011, health care and health communication experts came together in Rockville, Maryland under the auspices of the Agency for Healthcare Research and Quality (AHRQ) John M. Eisenberg Center for Clinical Decisions and Communications Science Annual Meeting to explore the challenges of differing levels of evidence in promoting shared decisions and to propose strategies for going forward in addressing these challenges. Eight scholarly papers emerged, and with this introductory article, comprise this special issue of Medical Care Research and Review.

  17. The influence of large wood accumulations on riparian seed bank diversity

    NASA Astrophysics Data System (ADS)

    Osei, N. A.

    2012-04-01

    Little is known about the structure and complexity of seed bank within the riparian corridor and the how large wood accumulations contribute to riparian seed bank diversity. This study aimed to examine and quantify seed bank assemblage and diversity along the undisturbed riparian corridor of the Highland Water, a second order lowland stream draining the New Forest. Seed bank samples were collected from five riparian corridor microhabitats namely mid-channel bars, floodplains, bare banks, banks adjacent large wood accumulations and within large wood accumulations that differed in their hydrologic connectivity with the river. Descriptive statistics and ordination methods applied to the floristic and sediment data sets indicates that sediment organic matter content, species richness and proportions of functional types distinctly differed among the riparian microhabitats types but there was no difference in viable seed densities. Banks adjacent large wood accumulations were the most floristically diverse and rich in organic matter with mid-channel bars exhibiting the reverse. This was due to the ability of large wood accumulations to buffer varying magnitudes of physical gradients and sort seeds and sediments, therefore altering the character of bare banks. This study not only strengthen the evidence that riparian corridors exhibit elevated spatial sediment and vegetation heterogeneity but also demonstrates the importance of large wood accumulation as habitat modifiers, ecosystem engineers and conservation sink for moisture, organic matter and seeds, resources essential for riparian vegetation conservation, recovery and restoration efforts.

  18. Accumulation of polyubiquitylated proteins in response to Ala-Ala-Phe-chloromethylketone is independent of the inhibition of Tripeptidyl peptidase II.

    PubMed

    Villasevil, Eugenia M; Guil, Sara; López-Ferreras, Lorena; Sánchez, Carlos; Del Val, Margarita; Antón, Luis C

    2010-09-01

    In the present study we have addressed the issue of proteasome independent cytosolic protein degradation. Tripeptidyl peptidase II (TPPII) has been suggested to compensate for a reduced proteasome activity, partly based on evidence using the inhibitor Ala-Ala-Phe-chloromethylketone (AAF-cmk). Here we show that AAF-cmk induces the formation of polyubiquitin-containing accumulations in osteosarcoma and Burkitt's lymphoma cell lines. These accumulations meet many of the landmarks of the aggresomes that form after proteasome inhibition. Using a combination of experiments with chemical inhibitors and interference of gene expression, we show that TPPII inhibition is not responsible for these accumulations. Our evidence suggests that the relevant target(s) is/are in the ubiquitin-proteasome pathway, most likely upstream the proteasome. We obtained evidence supporting this model by inhibition of Hsp90, which also acts upstream the proteasome. Although our data suggest that Hsp90 is not a target of AAF-cmk, its inhibition resulted in accumulations similar to those obtained with AAF-cmk. Therefore, our results question the proposed role for TPPII as a prominent alternative to the proteasome in cellular proteolysis. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Preferential Osmolyte Accumulation: a Mechanism of Osmotic Stress Adaptation in Diazotrophic Bacteria

    PubMed Central

    Madkour, Magdy A.; Smith, Linda Tombras; Smith, Gary M.

    1990-01-01

    A common cellular mechanism of osmotic-stress adaptation is the intracellular accumulation of organic solutes (osmolytes). We investigated the mechanism of osmotic adaptation in the diazotrophic bacteria Azotobacter chroococcum, Azospirillum brasilense, and Klebsiella pneumoniae, which are adversely affected by high osmotic strength (i.e., soil salinity and/or drought). We used natural-abundance 13C nuclear magnetic resonance spectroscopy to identify all the osmolytes accumulating in these strains during osmotic stress generated by 0.5 M NaCl. Evidence is presented for the accumulation of trehalose and glutamate in Azotobacter chroococcum ZSM4, proline and glutamate in Azospirillum brasilense SHS6, and trehalose and proline in K. pneumoniae. Glycine betaine was accumulated in all strains grown in culture media containing yeast extract as the sole nitrogen source. Alternative nitrogen sources (e.g., NH4Cl or casamino acids) in the culture medium did not result in measurable glycine betaine accumulation. We suggest that the mechanism of osmotic adaptation in these organisms entails the accumulation of osmolytes in hyperosmotically stressed cells resulting from either enhanced uptake from the medium (of glycine betaine, proline, and glutamate) or increased net biosynthesis (of trehalose, proline, and glutamate) or both. The preferred osmolyte in Azotobacter chroococcum ZSM4 shifted from glutamate to trehalose as a consequence of a prolonged osmotic stress. Also, the dominant osmolyte in Azospirillum brasilense SHS6 shifted from glutamate to proline accumulation as the osmotic strength of the medium increased. PMID:16348295

  20. Evidence and evidence gaps in therapies of nasal obstruction and rhinosinusitis

    PubMed Central

    Rotter, Nicole

    2016-01-01

    Therapeutic decisions in otorhinolaryngology are based on clinical experience, surgical skills, and scientific evidence. Recently, evidence-based therapies have gained increased attention and importance due to their potential to improve the individual patient’s treatment and their potential at the same time to reduce treatment costs. In clinical practice, it is almost impossible to stay ahead of the increasing mass of literature and on the other hand critically assess the presented data. A solid scientific and statistical knowledge as well as a significant amount of spare time are required to detect systematic bias and other errors in study designs, also with respect to assessing whether or not a study should be part of an individual therapeutic decision. Meta-analyses, reviews, and clinical guidelines are, therefore, of increasing importance for evidence-based therapy in clinical practice. This review is an update of the availability of external evidence for the treatment of nasal obstruction and rhinosinusitis. It becomes evident that both groups of diseases differ significantly in the availability of external evidence. Furthermore, it becomes obvious that surgical treatment options are normally based on evidence of significantly lower quality than medical treatment options. PMID:28025606

  1. Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research

    PubMed Central

    Kim, Hyungsuk; Clark, David; Dionne, Raymond A.

    2010-01-01

    Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388

  2. Accumulated α-synuclein affects the progression of GM2 gangliosidoses.

    PubMed

    Suzuki, Kyoko; Yamaguchi, Akira; Yamanaka, Shoji; Kanzaki, Seiichi; Kawashima, Masato; Togo, Takashi; Katsuse, Omi; Koumitsu, Noriko; Aoki, Naoya; Iseki, Eizo; Kosaka, Kenji; Yamaguchi, Kayoko; Hashimoto, Makoto; Aoki, Ichiro; Hirayasu, Yoshio

    2016-10-01

    The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSDs) but it remains unclear if ASyn accumulation contributes to LSD pathology. ASyn also accumulates in the neurons of Sandhoff disease (SD) patients and SD model mice (Hexb-/- ASyn+/+ mice). SD is a lysosomal storage disorder caused by the absence of a functional β-subunit on the β-hexosaminidase A and B enzymes, which leads to the accumulation of ganglioside in the central nervous system. Here, we explored the role of accumulated ASyn in the progression of Hexb-/- mice by creating a Hexb-/- ASyn-/- double-knockout mice. Our results show that Hexb-/- ASyn-/- mice demonstrated active microglia levels and less dopaminergic neuron loss, without altering the neuronal storage of ganglioside. The autophagy and ubiquitin proteasome pathways are defective in the neurons of Hexb-/- ASyn+/+ mice. In ultrastructural physiological studies, the mitochondria structures look degenerated and dysfunctional. As a result, expression of manganese superoxide dismutase 2 are reduced, and reactive oxygen species-mediated oxidative damage in the neurons of Hexb-/- ASyn+/+ mice. Interestingly, these dysfunctions improved in Hexb-/- ASyn-/- mice. But any clinical improvement were hardly observed in Hexb-/- ASyn-/- mice. Taken together, these findings suggest that ASyn accumulation plays an important role in the pathogenesis of neuropathy in SD and other LSDs, and is therefore a target for novel therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Lateral Augmentation Procedures in Anterior Cruciate Ligament Reconstruction: Anatomic, Biomechanical, Imaging, and Clinical Evidence.

    PubMed

    Weber, Alexander E; Zuke, William; Mayer, Erik N; Forsythe, Brian; Getgood, Alan; Verma, Nikhil N; Bach, Bernard R; Bedi, Asheesh; Cole, Brian J

    2018-02-01

    There has been an increasing interest in lateral-based soft tissue reconstructive techniques as augments to anterior cruciate ligament reconstruction (ACLR). The objective of these procedures is to minimize anterolateral rotational instability of the knee after surgery. Despite the relatively rapid increase in surgical application of these techniques, many clinical questions remain. To provide a comprehensive update on the current state of these lateral-based augmentation procedures by reviewing the origins of the surgical techniques, the biomechanical data to support their use, and the clinical results to date. Systematic review. A systematic search of the literature was conducted via the Medline, EMBASE, Scopus, SportDiscus, and CINAHL databases. The search was designed to encompass the literature on lateral extra-articular tenodesis (LET) procedures and the anterolateral ligament (ALL) reconstruction. Titles and abstracts were reviewed for relevance and sorted into the following categories: anatomy, biomechanics, imaging/diagnostics, surgical techniques, and clinical outcomes. The search identified 4016 articles. After review for relevance, 31, 53, 27, 35, 45, and 78 articles described the anatomy, biomechanics, imaging/diagnostics, surgical techniques, and clinical outcomes of either LET procedures or the ALL reconstruction, respectively. A multitude of investigations were available, revealing controversy in addition to consensus in several categories. The level of evidence obtained from this search was not adequate for systematic review or meta-analysis; thus, a current concepts review of the anatomy, biomechanics, imaging, surgical techniques, and clinical outcomes was performed. Histologically, the ALL appears to be a distinct structure that can be identified with advanced imaging techniques. Biomechanical evidence suggests that the anterolateral structures of the knee, including the ALL, contribute to minimizing anterolateral rotational instability

  4. Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

    PubMed Central

    Bejaimal, Shayna AD; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

    2013-01-01

    Background Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. Objective To compare the performance of searches in PubMed and Google Scholar. Methods We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Results Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). Conclusions For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles. PMID:23948488

  5. Re-accumulation of Asteroids to Equilibrium Figures

    NASA Astrophysics Data System (ADS)

    Hestroffer, D.; Tanga, P.; Richardson, D. C.; Berthier, J.; Cellino, A.; Durech, J.; Michel, P.

    2008-09-01

    Since their formation, asteroids since their formation have experienced little physical, geological or thermal evolution. Like comets they are thought to be among the most pristine remnants of the early solar system. One physical process, however, has played a major role since the ancient times: collisions. Dynamical families were produced by catastrophic collisions involving large enough energy to break the parent body. Other lines of evidence suggest that catastrophic collisions can also produce rubble-piles, i.e., loosely bound of post-collisional aggregates that re-accumulate to form a single body, and are kept together by gravity. The main objective of this work is to understand if—and under what conditions—Jacobi ellipsoids or other equilibrium figures can be obtained naturally by this way. This is done by performing numerical experiments simulating the re-accumulation process, and by performing high-angular resolution observations in order to better constrain the shape and density of the targets. It is shown that the outcomes of reaccumulation events tend to produce a rather narrow variety of possible shapes, and in some cases also binary systems.

  6. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment.

    PubMed

    Greenlee, Heather; DuPont-Reyes, Melissa J; Balneaves, Lynda G; Carlson, Linda E; Cohen, Misha R; Deng, Gary; Johnson, Jillian A; Mumber, Matthew; Seely, Dugald; Zick, Suzanna M; Boyce, Lindsay M; Tripathy, Debu

    2017-05-06

    Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

    PubMed

    Patel, Maxine X; Sethi, Faisil N; Barnes, Thomas Re; Dix, Roland; Dratcu, Luiz; Fox, Bernard; Garriga, Marina; Haste, Julie C; Kahl, Kai G; Lingford-Hughes, Anne; McAllister-Williams, Hamish; O'Brien, Aileen; Parker, Caroline; Paterson, Brodie; Paton, Carol; Posporelis, Sotiris; Taylor, David M; Vieta, Eduard; Völlm, Birgit; Wilson-Jones, Charlotte; Woods, Laura

    2018-06-01

    The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

  8. Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice.

    PubMed

    Howell, D; Oliver, T K; Keller-Olaman, S; Davidson, J R; Garland, S; Samuels, C; Savard, J; Harris, C; Aubin, M; Olson, K; Sussman, J; MacFarlane, J; Taylor, C

    2014-04-01

    Sleep disturbance is prevalent in cancer with detrimental effects on health outcomes. Sleep problems are seldom identified or addressed in cancer practice. The purpose of this review was to identify the evidence base for the assessment and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) for oncology practice. The search of the health literature included grey literature data sources and empirical databases from June 2004 to June 2012. The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers and guideline methodologists to develop clinical practice recommendations for pan-Canadian use reported in a separate paper. Three clinical practice guidelines and 12 randomized, controlled trials were identified as the main source of evidence. Additional guidelines and systematic reviews were also reviewed for evidence-based recommendations on the assessment and management of insomnia not necessarily in cancer. A need to routinely screen for sleep disturbances was identified and the randomized, controlled trial (RCT) evidence suggests benefits for cognitive behavioural therapy for improving sleep quality in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater recognition in clinical practice and in future research.

  9. Evaluation of evidence-based literature and formulation of recommendations for the clinical preventive guidelines for immigrants and refugees in Canada

    PubMed Central

    Tugwell, Peter; Pottie, Kevin; Welch, Vivian; Ueffing, Erin; Chambers, Andrea; Feightner, John

    2011-01-01

    Background: This article describes the evidence review and guideline development method developed for the Clinical Preventive Guidelines for Immigrants and Refugees in Canada by the Canadian Collaboration for Immigrant and Refugee Health Guideline Committee. Methods: The Appraisal of Guidelines for Research and Evaluation (AGREE) best-practice framework was combined with the recently developed Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to produce evidence-based clinical guidelines for immigrants and refugees in Canada. Results: A systematic approach was designed to produce the evidence reviews and apply the GRADE approach, including building on evidence from previous systematic reviews, searching for and comparing evidence between general and specific immigrant populations, and applying the GRADE criteria for making recommendations. This method was used for priority health conditions that had been selected by practitioners caring for immigrants and refugees in Canada. Interpretation: This article outlines the 14-step method that was defined to standardize the guideline development process for each priority health condition. PMID:20573711

  10. Use of evidence in the process of practice change in a clinical team: a study-forming part of the Autocontrol Project.

    PubMed

    Mehta, V; Kushniruk, A; Gauthier, S; Richard, Y; Deland, E; Veilleux, M; Grant, A

    1998-01-01

    The Autocontrol Project is concerned with the accessing, processing and communication of high quality information so that a clinical team can make and implement decisions for practice change, and then evaluate if improvement has been achieved. High quality information is used as evidence for change. In this study, we have evaluated how evidence is used by a clinical team to explain an identified problem of inappropriate use of blood gas tests. In an experimental study of the Surgical Intensive Care Unit, video recordings of team meetings of nurses and doctors were undertaken, structured according to a problem-based format. Evidence of current practice patterns derived from the hospital information system, as well as the results of a questionnaire to the unit's staff about knowledge and use of blood gas measurements, were supplied to the participants beforehand. At the second meeting, the output of the first meetings and a summarised analysis of pertinent literature were made available. This second meeting was required to finalise the list of causes of inappropriate blood gas use and propose pragmatic strategies for practice change. The video data of the meetings were coded to analyse the use of evidence, the categories of causes, issues and solutions proposed, and the quality of team interaction. The results indicate that in order to achieve consensus, the team used different types of evidence, including objective evidence of practice patterns, personal experience about direct and indirect organisational influences, and literature-based research evidence of best practice. Furthermore, group dynamics were favoured by the problem-based meeting structure, and a high level of cognitive critiquing between team members was observed. This research suggests that a combination of approaches involving identification of both operational factors (e.g. appropriate access to different types of evidence and meeting structure) and cognitive and behavioural approaches (e

  11. Teaching clinical reasoning to medical students.

    PubMed

    Gay, Simon; Bartlett, Maggie; McKinley, Robert

    2013-10-01

    Keele Medical School's new curriculum includes a 5-week course to extend medical students' consultation skills beyond those historically required for competent inductive diagnosis. Clinical reasoning is a core skill for the practice of medicine, and is known to have implications for patient safety, yet historically it has not been explicitly taught. Rather, it has been assumed that these skills will be learned by accumulating a body of knowledge and by observing expert clinicians. This course aims to assist students to develop their own clinical reasoning skills and promote their greater understanding of, and potential to benefit from, the clinical reasoning skills of others. The course takes place in the fourth or penultimate year, and is integrated with students' clinical placements, giving them opportunities to practise and quickly embed their learning. This course emphasises that clinical reasoning extends beyond initial diagnosis into all other aspects of clinical practice, particularly clinical management. It offers students a variety of challenging and interesting opportunities to engage with clinical reasoning across a wide range of clinical practice. It addresses bias through metacognition and increased self-awareness, considers some of the complexities of prescribing and non-pharmacological interventions, and promotes pragmatic evidence-based practice, information management within the consultation and the maximising of patient adherence. This article describes clinical reasoning-based classroom and community teaching. Early evaluation suggests that students value the course and benefit from it. © 2013 John Wiley & Sons Ltd.

  12. Mitochondrial accumulation of APP and Aβ: significance for Alzheimer disease pathogenesis

    PubMed Central

    Pavlov, Pavel F; Petersen, Camilla Hansson; Glaser, Elzbieta; Ankarcrona, Maria

    2009-01-01

    Accumulating evidence suggest that alterations in energy metabolism are among the earliest events that occur in the Alzheimer disease (AD) affected brain. Energy consumption is drastically decreased in the AD-affected regions of cerebral cortex and hippocampus pointing towards compromised mitochondrial function of neurons within specific brain regions. This is accompanied by an elevated production of reactive oxygen species contributing to increased rates of neuronal loss in the AD-affected brain regions. In this review, we will discuss the role of mitochondrial function and dysfunction in AD. We will focus on the consequences of amyloid precursor protein and amyloid-β peptide accumulation in mitochondria and their involvement in AD pathogenesis. PMID:19725915

  13. Iron accumulation in multiple sclerosis: an early pathogenic event.

    PubMed

    LeVine, Steven M; Bilgen, Mehmet; Lynch, Sharon G

    2013-03-01

    Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

  14. Lubiprostone in constipation: clinical evidence and place in therapy.

    PubMed

    Wilson, Nicholas; Schey, Ron

    2015-03-01

    Constipation is one of the most common function bowel disorders encountered by primary care providers and gastroenterologists. Disorders of chronic constipation, including irritable bowel syndrome with constipation, chronic idiopathic constipation, and opioid-induced chronic constipation, are associated with significant medical costs and a negative impact on quality of life. Although there is evidence supporting the effectiveness of some over-the-counter laxatives in chronic constipation, currently there is no evidence supporting lifestyle modification, dietary change or over-the-counter laxatives as effective long-term therapy for patients with chronic constipation. Lubiprostone is a prostaglandin-derived bicyclic fatty acid available to use for long-term treatment of constipation. Lubiprostone works by increasing intraluminal chloride ion secretion, which results in a passive influx of water and sodium, leading to increased intestinal peristalsis and colonic laxation with decreased intestinal stool transit time. Randomized, double-blind, placebo-controlled trials of lubiprostone in patients with chronic constipation, irritable bowel syndrome and opioid-induced constipation have shown it to be effective and free of serious adverse effects. The most common side effects associated with lubiprostone are mild to moderate nausea and diarrhea. Currently lubiprostone is approved for treatment of chronic constipation and opioid-induced constipation for men and women at 24 µg twice daily and for treatment of irritable bowel syndrome with constipation in women at 8 µg twice daily. Additional research continues to shed light on the molecular mechanisms of lubiprostone and further work may expand its clinical applications.

  15. 5-Aminolevulinic Acid Accumulation in a Cerebral Infarction Mimicking High-Grade Glioma.

    PubMed

    Behling, Felix; Hennersdorf, Florian; Bornemann, Antje; Tatagiba, Marcos; Skardelly, Marco

    2016-08-01

    5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue. A 64-year old woman presented with episodes of apraxia and a ring-enhancing lesion in postcontrast T1-weighted magnetic resonance sequences suggestive of high grade glioma. Strong fluorescence was observed during 5-ALA-guided resection. However, although the frozen section was inconclusive, the final histopathologic examination revealed a stage II cerebral infarction. 5-ALA accumulation in postischemic cerebral tissue should be considered for intended supramarginal resections near eloquent brain regions. Therefore, sufficient preoperative imaging should regularly include magnetic resonance imaging spectroscopy and perfusion sequences to ascertain the proper diagnosis. Moreover, further research is warranted to determine the role of 5-ALA accumulation in postischemic and inflammatory brain tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. An automated tool for an analysis of compliance to evidence-based clinical guidelines.

    PubMed

    Metfessel, B A

    2001-01-01

    Evidence-based clinical guidelines have been developed in an attempt to decrease practice variation and improve patient outcomes. Although a number of studies and a few commercial products have attempted to measure guideline compliance, there still exists a strong need for an automated product that can take as input large amounts of data and create systematic and detailed profiles of compliance to evidence-based guidelines. The Guideline Compliance Assessment Tool is a product presently under development in our group that will accept as input medical and pharmacy claims data and create a guideline compliance profile that assesses provider practice patterns as compared to evidence-based standards. The system components include an episode of care grouper to standardize classifications of illnesses, an evidence-based guideline knowledge base that potentially contains information on several hundred distinct conditions, a guideline compliance scoring system that emphasizes systematic guideline variance rather than random variances, and an advanced data warehouse that would allow drilling into specific areas of interest. As provider profiling begins to shift away from a primary emphasis on cost to an emphasis on quality, automated methods for measuring guideline compliance will become important in measuring provider performance and increasing guideline usage, consequently improving the standard of care and the potential for better patient outcomes.

  17. Evidence for the treatment of co-occurring stuttering and speech sound disorder: A clinical case series.

    PubMed

    Unicomb, Rachael; Hewat, Sally; Spencer, Elizabeth; Harrison, Elisabeth

    2017-06-01

    There is a paucity of evidence to guide treatment for children with co-occurring stuttering and speech sound disorder. Some guidelines suggest treating the two disorders simultaneously using indirect treatment approaches; however, the research supporting these recommendations is over 20 years old. In this clinical case series, we investigate whether these co-occurring disorders could be treated concurrently using direct treatment approaches supported by up-to-date, high-level evidence, and whether this could be done in an efficacious, safe and efficient manner. Five pre-school-aged participants received individual concurrent, direct intervention for both stuttering and speech sound disorder. All participants used the Lidcombe Program, as manualised. Direct treatment for speech sound disorder was individualised based on analysis of each child's sound system. At 12 months post commencement of treatment, all except one participant had completed the Lidcombe Program, and were less than 1.0% syllables stuttered on samples gathered within and beyond the clinic. These four participants completed Stage 1 of the Lidcombe Program in between 14 and 22 clinic visits, consistent with current benchmark data for this programme. At the same assessment point, all five participants exhibited significant increases in percentage of consonants correct and were in alignment with age-expected estimates of this measure. Further, they were treated in an average number of clinic visits that compares favourably with other research on treatment for speech sound disorder. These preliminary results indicate that young children with co-occurring stuttering and speech sound disorder may be treated concurrently using direct treatment approaches. This method of service delivery may have implications for cost and time efficiency and may also address the crucial need for early intervention in both disorders. These positive findings highlight the need for further research in the area and contribute to

  18. Recent Scientific Evidence and Technical Developments in Cardiovascular Computed Tomography.

    PubMed

    Marcus, Roy; Ruff, Christer; Burgstahler, Christof; Notohamiprodjo, Mike; Nikolaou, Konstantin; Geisler, Tobias; Schroeder, Stephen; Bamberg, Fabian

    2016-05-01

    In recent years, coronary computed tomography angiography has become an increasingly safe and noninvasive modality for the evaluation of the anatomical structure of the coronary artery tree with diagnostic benefits especially in patients with a low-to-intermediate pretest probability of disease. Currently, increasing evidence from large randomized diagnostic trials is accumulating on the diagnostic impact of computed tomography angiography for the management of patients with acute and stable chest pain syndrome. At the same time, technical advances have substantially reduced adverse effects and limiting factors, such as radiation exposure, the amount of iodinated contrast agent, and scanning time, rendering the technique appropriate for broader clinical applications. In this work, we review the latest developments in computed tomography technology and describe the scientific evidence on the use of cardiac computed tomography angiography to evaluate patients with acute and stable chest pain syndrome. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  19. MARRIAGE AND MEN’S WEALTH ACCUMULATION IN THE UNITED STATES, 1860-1870

    PubMed Central

    HONG, SOK CHUL

    2013-01-01

    This paper explores how changes in marital status affected men’s wealth accumulation in mid-nineteenth-century America, using a longitudinal sample of Union Army veterans linked to the 1860 and 1870 census manuscript schedules. Controlling for the endogeneity of wealth and marital selection, this paper provides strong evidence that marriage had positive effects on men’s wealth accumulation, whereas ending a marriage had negative effects. The estimated wealth premium on married men is about 60 percent per marital year. This substantial wealth premium is closely related to wives’ specializing in household production, and farmers and craftsmen economically benefited from the unpaid labor of their wives. PMID:24058226

  20. Demise of reef-flat carbonate accumulation with late Holocene sea-level fall: Evidence from Molokai, Hawaii

    USGS Publications Warehouse

    Engels, M.S.; Fletcher, C.H.; Field, M.; Conger, C.L.; Bochicchio, C.

    2008-01-01

    Twelve cores from the protected reef-flat of Molokai revealed that carbonate sediment accumulation, ranging from 3 mm year-1 to less than 1 mm year-1, ended on average 2,500 years ago. Modern sediment is present as a mobile surface veneer but is not trapped within the reef framework. This finding is consistent with the arrest of deposition at the end of the mid-Holocene highstand, known locally as the "Kapapa Stand of the Sea," ???2 m above the present datum ca. 3,500 years ago in the main Hawaiian Islands. Subsequent erosion, non-deposition, and/or a lack of rigid binding were probable factors leading to the lack of reef-flat accumulation during the late Holocene sea-level fall. Given anticipated climate changes, increased sedimentation of reef-flat environments is to be expected as a consequence of higher sea level. ?? 2008 Springer-Verlag.

  1. Evidence review: the clinical benefits of Safetac technology in wound care.

    PubMed

    Davies, Phil; Rippon, Mark

    2008-11-01

    Common causes of trauma and wound pain include: the removal of dressings that become stuck to the wound bed; skin stripping of peri-wound skin, as a result of the repeated application and removal of adhesive dressings; and tissue excoriation and maceration of the peri-wound skin, due to inadequate management of wound exudate. This supplement outlines how dressings with Safetac adhesive technology can help clinicians to avoid these problems. A review of the clinical and scientific evidence relating to dressings with Safetac clearly demonstrates that they can be used to prevent trauma and minimise pain on a wide range of wound types and skin injuries.

  2. Levels of Evidence in the Clinical Sports Medicine Literature: Are We Getting Better Over Time?

    PubMed

    Grant, Heather M; Tjoumakaris, Fotios P; Maltenfort, Mitchell G; Freedman, Kevin B

    2014-07-01

    There has been an increased emphasis on improving the level of evidence used as the basis for clinical treatment decisions. Several journals now require a statement of the level of evidence as a basic gauge of the study's strength. To review the levels of evidence in published articles in the clinical sports medicine literature and to determine if there has been an improvement in the levels of evidence published over the past 15 years. Systematic review. All articles from the years 1995, 2000, 2005, and 2010 in The American Journal of Sports Medicine (AJSM), Arthroscopy, and sports medicine-related articles from The Journal of Bone and Joint Surgery-American (JBJS-A) were analyzed. Articles were categorized by type and ranked for level of evidence according to guidelines from the Centre for Evidence-Based Medicine. Excluded were animal, cadaveric, and basic science articles; editorials; surveys; special topics; letters to the editor; and correspondence. Statistical analysis was performed with chi-square. A total of 1580 articles over the 4 periods met the inclusion criteria. The percentage of level 1 and 2 studies increased from 6.8% to 12.6%, 22.9%, and 23.5%, respectively (P < .0001), while level 4 and 5 studies decreased from 78.9% to 72.4%, 63.9%, and 53.0% (P < .0001). JBJS-A had a significant increase in level 1 and 2 studies (4.1%, 5.1%, 28.2%, 27.8%; P < .0001), as did AJSM (9.4%, 17.1%, 36.1%, 30.1%; P < .0001). Arthroscopy showed no significant change over time. Diagnostic, therapeutic, and prognostic studies all showed significant increases in level 1 and 2 studies over time (P < .05). There has been a statistically significant increase in the percentage of level 1 and 2 studies published in the sports medicine literature over the past 15 years, particularly in JBJS-A and AJSM. The largest increase was seen in diagnostic studies, while therapeutic and prognostic studies demonstrated modest improvement. The emphasis on increasing levels of evidence to

  3. Lifespan mercury accumulation pattern in Liza aurata : Evidence from two southern European estuaries

    NASA Astrophysics Data System (ADS)

    Tavares, S.; Oliveira, H.; Coelho, J. P.; Pereira, M. E.; Duarte, A. C.; Pardal, M. A.

    2011-10-01

    Mercury accumulation throughout the lifespan of Liza aurata (Risso, 1810) was analysed in four tissues (muscle, gills, liver and brain) in two southern European coastal ecosystems with distinct mercury contamination. Specimens from four to five age classes were captured in two sampling sites in the Ria de Aveiro (Laranjo bay and Mira), a system historically contaminated by industrial mercury, and in one site in the Mondego estuary, assumed as a mercury-free ecosystem. Mercury concentration in all tissues was found to be significantly higher in the Ria de Aveiro (Laranjo bay) compared to the Mondego, in accordance with the environmental contamination (water, sediments and suspended particulate matter). Significant differences inside the Ria de Aveiro (between the Mira and Laranjo bay) were only detected in the liver. This tissue registered the highest levels of mercury (ranging from 0.11 to 4.2 μg g -1 ) in all sampling sites, followed by muscle, brain, and gills. In all sampling sites and tissues was denoted a mercury dilution pattern along the lifecycle (except in liver at the Mondego, the reference area where the concentrations are always very low). An exponential trend was found in the metal age variation patterns in Laranjo (the most contaminated area) and a linear trend in the Mira and the Mondego (the least contaminated areas). Organic mercury concentration in muscle generally accounted for over 95% of total mercury concentration, and followed the same accumulation pattern of total mercury. This fish species is of lesser importance in mercury transfer to adjacent coastal areas and although the consumption of fish from Laranjo may present some risk for the humans, this risk decreases with fish age/size.

  4. Effect of Clinically Discriminating, Evidence-Based Checklist Items on the Reliability of Scores from an Internal Medicine Residency OSCE

    ERIC Educational Resources Information Center

    Daniels, Vijay J.; Bordage, Georges; Gierl, Mark J.; Yudkowsky, Rachel

    2014-01-01

    Objective structured clinical examinations (OSCEs) are used worldwide for summative examinations but often lack acceptable reliability. Research has shown that reliability of scores increases if OSCE checklists for medical students include only clinically relevant items. Also, checklists are often missing evidence-based items that high-achieving…

  5. Using evidence-based algorithms to improve clinical decision making: the case of a first-time anterior shoulder dislocation.

    PubMed

    Federer, Andrew E; Taylor, Dean C; Mather, Richard C

    2013-09-01

    Decision making in health care has evolved substantially over the last century. Up until the late 1970s, medical decision making was predominantly intuitive and anecdotal. It was based on trial and error and involved high levels of problem solving. The 1980s gave way to empirical medicine, which was evidence based probabilistic, and involved pattern recognition and less problem solving. Although this represented a major advance in the quality of medical decision making, limitations existed. The advantages of the gold standard of the randomized controlled clinical trial (RCT) are well-known and this technique is irreplaceable in its ability to answer critical clinical questions. However, the RCT does have drawbacks. RCTs are expensive and can only capture a snapshot in time. As treatments change and new technologies emerge, new expensive clinical trials must be undertaken to reevaluate them. Furthermore, in order to best evaluate a single intervention, other factors must be controlled. In addition, the study population may not match that of another organization or provider. Although evidence-based medicine has provided powerful data for clinicians, effectively and efficiently tailoring it to the individual has not yet evolved. We are now in a period of transition from this evidence-based era to one dominated by the personalization and customization of care. It will be fueled by policy decisions to shift financial responsibility to the patient, creating a powerful and sophisticated consumer, unlike any patient we have known before. The challenge will be to apply medical evidence and personal preferences to medical decisions and deliver it efficiently in the increasingly busy clinical setting. In this article, we provide a robust review of the concepts of customized care and some of techniques to deliver it. We will illustrate this through a personalized decision model for the treatment decision after a first-time anterior shoulder dislocation.

  6. Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience.

    PubMed

    Farmakis, Dimitrios; Bistola, Vassiliki; Karavidas, Apostolos; Parissis, John

    2016-11-15

    The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Clinical Evidence for Spinal Cord Stimulation for Failed Back Surgery Syndrome (FBSS): Systematic Review.

    PubMed

    Kapural, Leonardo; Peterson, Erika; Provenzano, David A; Staats, Peter

    2017-07-15

    A systematic review. A systematic literature review of the clinical data from prospective studies was undertaken to assess the efficacy of spinal cord stimulation (SCS) in the treatment of failed back surgery syndrome (FBSS) in adults. For patients with unrelenting back pain due to mechanical instability of the spine, degenerative disc disease, spinal injury, or deformity, spinal surgery is a well-accepted treatment option; however, even after surgical intervention, many patients continue to experience chronic back pain that can be notoriously difficult to treat. Clinical evidence suggests that for patients with FBSS, repeated surgery will not likely offer relief. Additionally, evidence suggests long-term use of opioid pain medications is not effective in this population, likely presents additional complications, and requires strict management. A systematic literature review was performed using several bibliographic databases, prospective studies in adults using SCS for FBSS were included. SCS has been shown to be a safe and efficacious treatment for this patient population. Recent technological developments in SCS offer even greater pain relief to patients' refractory to other treatment options, allowing patients to regain functionality and improve their quality of life with significant reductions in pain. N/A.

  8. Can clinical governance deliver quality improvement in Australian general practice and primary care? A systematic review of the evidence.

    PubMed

    Phillips, Christine B; Pearce, Christopher M; Hall, Sally; Travaglia, Joanne; de Lusignan, Simon; Love, Tom; Kljakovic, Marjan

    2010-11-15

    To review the literature on different models of clinical governance and to explore their relevance to Australian primary health care, and their potential contributions on quality and safety. 25 electronic databases, scanning reference lists of articles and consultation with experts in the field. We searched publications in English after 1999, but a search of the German language literature for a specific model type was also undertaken. The grey literature was explored through a hand search of the medical trade press and websites of relevant national and international clearing houses and professional or industry bodies. 11 software packages commonly used in Australian general practice were reviewed for any potential contribution to clinical governance. 19 high-quality studies that assessed outcomes were included. All abstracts were screened by one researcher, and 10% were screened by a second researcher to crosscheck screening quality. Studies were reviewed and coded by four reviewers, with all studies being rated using standard critical appraisal tools such as the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two researchers reviewed the Australian general practice software. Interviews were conducted with 16 informants representing service, regional primary health care, national and international perspectives. Most evidence supports governance models which use targeted, peer-led feedback on the clinician's own practice. Strategies most used in clinical governance models were audit, performance against indicators, and peer-led reflection on evidence or performance. The evidence base for clinical governance is fragmented, and focuses mainly on process rather than outcomes. Few publications address models that enhance safety, efficiency, sustainability and the economics of primary health care. Locally relevant clinical indicators, the use of computerised medical record systems, regional primary health care organisations that have the

  9. Knowledge of and Attitudes Toward Evidence-Based Guidelines for and Against Clinical Preventive Services: Results from a National Survey.

    PubMed

    Lantz, Paula M; Evans, W Douglas; Mead, Holly; Alvarez, Carmen; Stewart, Lisa

    2016-03-01

    Both the underuse and overuse of clinical preventive services relative to evidence-based guidelines are a public health concern. Informed consumers are an important foundation of many components of the Affordable Care Act, including coverage mandates for proven clinical preventive services recommended by the US Preventive Services Task Force. Across sociodemographic groups, however, knowledge of and positive attitudes toward evidence-based guidelines for preventive care are extremely low. Given the demonstrated low levels of consumers' knowledge of and trust in guidelines, coupled with their strong preference for involvement in preventive care decisions, better education and decision-making support for evidence-based preventive services are greatly needed. Both the underuse and overuse of clinical preventive services are a serious public health problem. The goal of our study was to produce population-based national data that could assist in the design of communication strategies to increase knowledge of and positive attitudes toward evidence-based guidelines for clinical preventive services (including the US Preventive Services Task Force, USPSTF) and to reduce uncertainty among patients when guidelines change or are controversial. In late 2013 we implemented an Internet-based survey of a nationally representative sample of 2,529 adults via KnowledgePanel, a probability-based survey panel of approximately 60,000 adults, statistically representative of the US noninstitutionalized population. African Americans, Hispanics, and those with less than a high school education were oversampled. We then conducted descriptive statistics and multivariable logistic regression analysis to identify the prevalence of and sociodemographic characteristics associated with key knowledge and attitudinal variables. While 36.4% of adults reported knowing that the Affordable Care Act requires insurance companies to cover proven preventive services without cost sharing, only 7.7% had heard

  10. Character, paleoenvironment, rate of accumulation, and evidence for seismic triggering of Holocene turbidites, Canada Abyssal Plain, Arctic Ocean

    USGS Publications Warehouse

    Grantz, A.; Phillips, R.L.; Mullen, M.W.; Starratt, S.W.; Jones, Glenn A.; Naidu, A.S.; Finney, B.P.

    1996-01-01

    Four box cores and one piston core show that Holocene sedimentation on the southern Canada Abyssal Plain for the last 8010??120 yr has consisted of a continuing rain of pelagic organic and ice-rafted elastic sediment with a net accumulation rate during the late Holocene of ???10 mm/1000 yr, and episodically emplaced turbidites 1-5 m thick deposited at intervals of 830 to 3450 yr (average 2000 yr). The average net accumulation rate of the mixed sequence of turbidites and thin pelagite interbeds in the cores is about 1.2 m/1000 yr. Physiography suggests that the turbidites originated on the Mackenzie Delta or its clinoform, and ??13C values of -27 to - 25??? in the turbidites are compatible with a provenance on a delta. Extant displaced neritic and lower slope to basin plain calcareous benthic foraminifers coexist in the turbidite units. Their joint occurence indicates that the turbidites originated on the modern continental shelf and entrained sediment from the slope and rise enroute to their final resting place on the Canada Abyssal Plain. The presence of Middle Pleistocene diatoms in the turbidites suggests, in addition, that the turbidites may have originated in shallow submarine slides beneath the upper slope or outer shelf. Small but consistent differences in organic carbon content and ??13C values between the turbidite units suggest that they did not share an identical provenance, which is at least compatible with an origin in slope failures. The primary provenance of the ice-rafted component of the pelagic beds was the glaciated terrane of northwestern Canada; and the provenance of the turbidite units was Pleistocene and Holocene sedimentary deposits on the outer continental shelf and upper slope of the Mackenzie Delta. Largely local derivation of the sediment of the Canada Abyssal Plain indicates that sediment accumulation rates in the Arctic Ocean are valid only for regions with similar depositional sources and processes, and that these rates cannot be

  11. Masked nonword repetition effects in yes/no and go/no-go lexical decision: a test of the evidence accumulation and deadline accounts.

    PubMed

    Perea, Manuel; Gómez, Pablo; Fraga, Isabel

    2010-06-01

    The pattern of masked repetition priming effects for word and nonword targets differs across tasks: Masked-priming effects in lexical decision occur for positive responses (i.e., words), but not for negative responses (nonwords), whereas masked-priming effects in the cross-case same-different task occur for positive responses (same), but not for negative responses (different)--regardless of lexical status. Here, we examined whether masked nonword priming effects are greater when the task involves an active go response to nonwords than when it involves the standard yes/no procedure in lexical decision. The obtained masked repetition priming effect for nonwords was of similar size in yes/no and go/no-go tasks. This finding is compatible with accounts of nonword priming that posit that nonword responses are produced by actively accumulating evidence for the nonword alternative in yes/no and go/no-go procedures, whereas it is inconsistent with the assumption of a deadline for no responses in the yes/no task.

  12. Delay in micro-discharges appearance during PEO of Al: Evidence of a mechanism of charge accumulation at the electrolyte/oxide interface

    NASA Astrophysics Data System (ADS)

    Martin, J.; Nominé, A.; Brochard, F.; Briançon, J.-L.; Noël, C.; Belmonte, T.; Czerwiec, T.; Henrion, G.

    2017-07-01

    PEO was conducted on Al by applying a pulsed bipolar current. The role of the cathodic polarization on the appearance of micro-discharges (MDs) and on the subsequent formation of the PEO oxide layers is investigated. Various ratios of the charge quantity RCQ = Qp/Qn (defined as the anodic Qp to cathodic Qn charge quantity ratio over one current pulse period) in the range [0.5; 6.0] were selected by changing the waveform parameters of the cathodic current while keeping the waveform of the anodic current unchanged. Results show that the appearance of MDs is delayed with respect to the rising edge of the anodic current; this delay strongly depends on both the processing time and the applied cathodic charge quantity. It is also evidenced that shorter delays promoted by high RCQ values (RCQ > 1) are associated with stronger MDs (large size and long life) that have detrimental effects on the formed PEO oxide layers. Thicker and the more compact oxide layer morphology is achieved with the intermediate RCQ value (RCQ = 0.9) for which the delay of the MDs appearance is high and the MDs softer. Low RCQ (RCQ < 0.9) results in an earlier extinction of the MDs as the process goes on, which leads to poorly oxidized metal. A mechanism of charge accumulation taking place at the oxide/electrolyte interface and arising before the occurrence of dielectric breakdown is proposed to explain the ignition of MDs during pulsed bipolar PEO of aluminium. A close examination of the voltage-time response which can be adequately simulated with an equivalent RC circuit evidences the capacitive behaviour of the oxide layer and therefore confirms this proposed mechanism of charge accumulation.

  13. Tips for Teachers of Evidence-based Medicine: Clinical Prediction Rules (CPRs) and Estimating Pretest Probability

    PubMed Central

    McGinn, Thomas; Jervis, Ramiro; Wisnivesky, Juan; Keitz, Sheri

    2008-01-01

    Background Clinical prediction rules (CPR) are tools that clinicians can use to predict the most likely diagnosis, prognosis, or response to treatment in a patient based on individual characteristics. CPRs attempt to standardize, simplify, and increase the accuracy of clinicians’ diagnostic and prognostic assessments. The teaching tips series is designed to give teachers advice and materials they can use to attain specific educational objectives. Educational Objectives In this article, we present 3 teaching tips aimed at helping clinical learners use clinical prediction rules and to more accurately assess pretest probability in every day practice. The first tip is designed to demonstrate variability in physician estimation of pretest probability. The second tip demonstrates how the estimate of pretest probability influences the interpretation of diagnostic tests and patient management. The third tip exposes learners to various examples and different types of Clinical Prediction Rules (CPR) and how to apply them in practice. Pilot Testing We field tested all 3 tips with 16 learners, a mix of interns and senior residents. Teacher preparatory time was approximately 2 hours. The field test utilized a board and a data projector; 3 handouts were prepared. The tips were felt to be clear and the educational objectives reached. Potential teaching pitfalls were identified. Conclusion Teaching with these tips will help physicians appreciate the importance of applying evidence to their every day decisions. In 2 or 3 short teaching sessions, clinicians can also become familiar with the use of CPRs in applying evidence consistently in everyday practice. PMID:18491194

  14. Clinical practice guideline development manual: A quality-driven approach for translating evidence into action

    PubMed Central

    Rosenfeld, Richard M.; Shiffman, Richard N.

    2010-01-01

    Background Guidelines translate best evidence into best practice. A well-crafted guideline promotes quality by reducing healthcare variations, improving diagnostic accuracy, promoting effective therapy, and discouraging ineffective – or potentially harmful – interventions. Despite a plethora of published guidelines, methodology is often poorly defined and varies greatly within and among organizations. Purpose This manual describes the principles and practices used successfully by the American Academy of Otolaryngology – Head and Neck Surgery to produce quality-driven, evidence-based guidelines using efficient and transparent methodology for action-ready recommendations with multi-disciplinary applicability. The development process, which allows moving from conception to completion in twelve months, emphasizes a logical sequence of key action statements supported by amplifying text, evidence profiles, and recommendation grades that link action to evidence. Conclusions As clinical practice guidelines become more prominent as a key metric of quality healthcare, organizations must develop efficient production strategies that balance rigor and pragmatism. Equally important, clinicians must become savvy in understanding what guidelines are – and are not – and how they are best utilized to improve care. The information in this manual should help clinicians and organizations achieve these goals. PMID:19464525

  15. Clinical practice guideline development manual: a quality-driven approach for translating evidence into action.

    PubMed

    Rosenfeld, Richard M; Shiffman, Richard N

    2009-06-01

    Guidelines translate best evidence into best practice. A well-crafted guideline promotes quality by reducing health-care variations, improving diagnostic accuracy, promoting effective therapy, and discouraging ineffective-or potentially harmful-interventions. Despite a plethora of published guidelines, methodology is often poorly defined and varies greatly within and among organizations. This manual describes the principles and practices used successfully by the American Academy of Otolaryngology-Head and Neck Surgery to produce quality-driven, evidence-based guidelines using efficient and transparent methodology for action-ready recommendations with multidisciplinary applicability. The development process, which allows moving from conception to completion in 12 months, emphasizes a logical sequence of key action statements supported by amplifying text, evidence profiles, and recommendation grades that link action to evidence. As clinical practice guidelines become more prominent as a key metric of quality health care, organizations must develop efficient production strategies that balance rigor and pragmatism. Equally important, clinicians must become savvy in understanding what guidelines are-and are not-and how they are best utilized to improve care. The information in this manual should help clinicians and organizations achieve these goals.

  16. The biomedical disciplines and the structure of biomedical and clinical knowledge.

    PubMed

    Nederbragt, H

    2000-11-01

    The relation between biomedical knowledge and clinical knowledge is discussed by comparing their respective structures. The knowledge of a disease as a biological phenomenon is constructed by the interaction of facts and theories from the main biomedical disciplines: epidemiology, diagnostics, clinical trial, therapy development and pathogenesis. Although these facts and theories are based on probabilities and extrapolations, the interaction provides a reliable and coherent structure, comparable to a Kuhnian paradigma. In the structure of clinical knowledge, i.e. knowledge of the patient with the disease, not only biomedical knowledge contributes to the structure but also economic and social relations, ethics and personal experience. However, the interaction between each of the participating "knowledges" in clinical knowledge is not based on mutual dependency and accumulation of different arguments from each, as in biomedical knowledge, but on competition and partial exclusion. Therefore, the structure of biomedical knowledge is different from that of clinical knowledge. This difference is used as the basis for a discussion in which the place of technology, evidence-based medicine and the gap between scientific and clinical knowledge are evaluated.

  17. General practitioners, complementary therapies and evidence-based medicine: the defence of clinical autonomy.

    PubMed

    Adams, J

    2000-12-01

    Amidst the substantial change currently gripping primary health care are two developments central to contemporary debate regarding the very nature, territory and identity of general practice - the integration of complementary and alternative medicine (CAM) and the rise of evidence-based medicine (EBM). This paper reports findings from a study based upon 25 in-depth interviews with general practitioners (GPs) personally practising complementary therapies alongside more conventional medicine to treat their NHS patients. The paper outlines the GPs' perceptions of EBM, its relationship to their personal development of CAM, and their notions of good clinical practice more generally. Analysis of the GPs' accounts demonstrates how CAM can be seen as a useful resource with which some GPs defend their clinical autonomy from what they perceive to be the threat of EBM. Copyright 2000 Harcourt Publishers Ltd.

  18. Clinical research evidence of cupping therapy in China: a systematic literature review

    PubMed Central

    2010-01-01

    Background Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it. This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. Methods We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. Results 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. Conclusions According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice. PMID:21078197

  19. Clinical research evidence of cupping therapy in China: a systematic literature review.

    PubMed

    Cao, Huijuan; Han, Mei; Li, Xun; Dong, Shangjuan; Shang, Yongmei; Wang, Qian; Xu, Shu; Liu, Jianping

    2010-11-16

    Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it.This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice.

  20. Grading the quality of evidence and the strength of recommendations in clinical dentistry: a critical review of 2 prominent approaches.

    PubMed

    Faggion, Clovis Mariano

    2010-06-01

    The objective of this article was to critically review 2 prominent approaches used to grade the quality of evidence and the strength of recommendations. Every year much information becomes available as a result of publication of scientific papers, and clinicians should be able to assess current evidence so they, along with their patients, can make the most appropriate clinical decisions. This is particularly important when there is little or no high-quality evidence available about the subject of interest. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the Strength of Recommendation Taxonomy (SORT) were evaluated. Strengths and weaknesses of these 2 systems are discussed, mainly on the basis of their relevance to clinical dentistry. The conclusion was that use of a system for grading the quality of evidence and the strength of recommendations is urgently required because of the great heterogeneity of the quality and type of evidence relating to many dental procedures. Use of such a system will enable clinicians and their patients to make more informed decisions.

  1. Evidence-based periodontal therapy: An overview

    PubMed Central

    Vijayalakshmi, R.; Anitha, V.; Ramakrishnan, T.; Sudhakar, Uma

    2008-01-01

    Dentists need to make clinical decisions based on limited scientific evidence. In clinical practice, a clinician must weigh a myriad of evidences every day. The goal of evidence-based dentistry is to help practitioners provide their patients with optimal care. This is achieved by integrating sound research evidence with personal clinical expertise and patient values to determine the best course of treatment. Periodontology has a rich background of research and scholarship. Therefore, efficient use of this wealth of research data needs to be a part of periodontal practice. Evidence-based periodontology aims to facilitate such an approach and it offers a bridge from science to clinical practice. The clinician must integrate the evidence with patient preference, scientific knowledge, and personal experience. Most important, it allows us to care for our patients. Therefore, evidence-based periodontology is a tool to support decision-making and integrating the best evidence available with clinical practice. PMID:20142947

  2. Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children.

    PubMed

    Berni Canani, R; Cucchiara, S; Cuomo, R; Pace, F; Papale, F

    2011-07-01

    Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed.

  3. Mineral transformation and biomass accumulation associated with uranium bioremediation at Rifle, Colorado

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, L.; Steefel, C.I.; Williams, K.H.

    2009-04-20

    Injection of organic carbon into the subsurface as an electron donor for bioremediation of redox-sensitive contaminants like uranium often leads to mineral transformation and biomass accumulation, both of which can alter the flow field and potentially bioremediation efficacy. This work combines reactive transport modeling with a column experiment and field measurements to understand the biogeochemical processes and to quantify the biomass and mineral transformation/accumulation during a bioremediation experiment at a uranium contaminated site near Rifle, Colorado. We use the reactive transport model CrunchFlow to explicitly simulate microbial community dynamics of iron and sulfate reducers, and their impacts on reaction rates.more » The column experiment shows clear evidence of mineral precipitation, primarily in the form of calcite and iron monosulfide. At the field scale, reactive transport simulations suggest that the biogeochemical reactions occur mostly close to the injection wells where acetate concentrations are highest, with mineral precipitate and biomass accumulation reaching as high as 1.5% of the pore space. This work shows that reactive transport modeling coupled with field data can be an effective tool for quantitative estimation of mineral transformation and biomass accumulation, thus improving the design of bioremediation strategies.« less

  4. Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons.

    PubMed

    Fukui, Hirokazu; Moraes, Carlos T

    2009-03-15

    Age-dependent accumulation of partially deleted mitochondrial DNA (DeltamtDNA) has been suggested to contribute to aging and the development of age-associated diseases including Parkinson's disease. However, the molecular mechanisms underlying the generation and accumulation of DeltamtDNA have not been addressed in vivo. In this study, we have developed a mouse model expressing an inducible mitochondria-targeted restriction endonuclease (PstI). Using this system, we could trigger mtDNA double-strand breaks (DSBs) in adult neurons. We found that this transient event leads to the generation of a family of DeltamtDNA with features that closely resemble naturally-occurring mtDNA deletions. The formation of these deleted species is likely to be mediated by yet uncharacterized DNA repairing machineries that participate in homologous recombination and non-homologous end-joining. Furthermore, we obtained in vivo evidence that DeltamtDNAs with larger deletions accumulate faster than those with smaller deletions, implying a replicative advantage of smaller mtDNAs. These findings identify DSB, DNA repair systems and replicative advantage as likely mechanisms underlying the generation and age-associated accumulation of DeltamtDNA in mammalian neurons.

  5. Mineral transformation and biomass accumulation associated with uranium bioremediation at Rifle, Colorado.

    PubMed

    Li, Li; Steefel, Carl I; Williams, Kenneth H; Wilkins, Michael J; Hubbard, Susan S

    2009-07-15

    Injection of organic carbon into the subsurface as an electron donor for bioremediation of redox-sensitive contaminants like uranium often leads to mineral transformation and biomass accumulation, both of which can alter the flow field and potentially bioremediation efficacy. This work combines reactive transport modeling with a column experiment and field measurements to understand the biogeochemical processes and to quantify the biomass and mineral transformation/accumulation during a bioremediation experiment at a uranium contaminated site near Rifle, Colorado. We use the reactive transport model CrunchFlow to explicitly simulate microbial community dynamics of iron and sulfate reducers, and their impacts on reaction rates. The column experiment shows clear evidence of mineral precipitation, primarily in the form of calcite and iron monosulfide. At the field scale, reactive transport simulations suggest that the biogeochemical reactions occur mostly close to the injection wells where acetate concentrations are highest, with mineral precipitate and biomass accumulation reaching as high as 1.5% of the pore space. This work shows that reactive transport modeling coupled with field data can bean effective tool for quantitative estimation of mineral transformation and biomass accumulation, thus improving the design of bioremediation strategies.

  6. Lubiprostone in constipation: clinical evidence and place in therapy

    PubMed Central

    Wilson, Nicholas

    2015-01-01

    Constipation is one of the most common function bowel disorders encountered by primary care providers and gastroenterologists. Disorders of chronic constipation, including irritable bowel syndrome with constipation, chronic idiopathic constipation, and opioid-induced chronic constipation, are associated with significant medical costs and a negative impact on quality of life. Although there is evidence supporting the effectiveness of some over-the-counter laxatives in chronic constipation, currently there is no evidence supporting lifestyle modification, dietary change or over-the-counter laxatives as effective long-term therapy for patients with chronic constipation. Lubiprostone is a prostaglandin-derived bicyclic fatty acid available to use for long-term treatment of constipation. Lubiprostone works by increasing intraluminal chloride ion secretion, which results in a passive influx of water and sodium, leading to increased intestinal peristalsis and colonic laxation with decreased intestinal stool transit time. Randomized, double-blind, placebo-controlled trials of lubiprostone in patients with chronic constipation, irritable bowel syndrome and opioid-induced constipation have shown it to be effective and free of serious adverse effects. The most common side effects associated with lubiprostone are mild to moderate nausea and diarrhea. Currently lubiprostone is approved for treatment of chronic constipation and opioid-induced constipation for men and women at 24 µg twice daily and for treatment of irritable bowel syndrome with constipation in women at 8 µg twice daily. Additional research continues to shed light on the molecular mechanisms of lubiprostone and further work may expand its clinical applications. PMID:25729555

  7. Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia.

    PubMed

    Teipel, Stefan; König, Alexandra; Hoey, Jesse; Kaye, Jeff; Krüger, Frank; Robillard, Julie M; Kirste, Thomas; Babiloni, Claudio

    2018-06-21

    Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials. Copyright © 2018. Published by Elsevier Inc.

  8. Carbon isotope evidence for recent climate-related enhancement of CO 2 assimilation and peat accumulation rates in Antarctica.

    PubMed

    Royles, Jessica; Ogée, Jérôme; Wingate, Lisa; Hodgson, Dominic A; Convey, Peter; Griffiths, Howard

    2012-10-01

    Signy Island, maritime Antarctic, lies within the region of the Southern Hemisphere that is currently experiencing the most rapid rates of environmental change. In this study, peat cores up to 2 m in depth from four moss banks on Signy Island were used to reconstruct changes in moss growth and climatic characteristics over the late Holocene. Measurements included radiocarbon dating (to determine peat accumulation rates) and stable carbon isotope composition of moss cellulose (to estimate photosynthetic limitation by CO 2 supply and model CO 2 assimilation rate). For at least one intensively 14 C-dated Chorisodontium aciphyllum moss peat bank, the vertical accumulation rate of peat was 3.9 mm yr -1 over the last 30 years. Before the industrial revolution, rates of peat accumulation in all cores were much lower, at around 0.6-1 mm yr -1 . Carbon-13 discrimination (Δ), corrected for background and anthropogenic source inputs, was used to develop a predictive model for CO 2 assimilation. Between 1680 and 1900, there had been a gradual increase in Δ, and hence assimilation rate. Since 1800, assimilation has also been stimulated by the changes in atmospheric CO 2 concentration, but a recent decline in Δ (over the past 50-100 years) can perhaps be attributed to documented changes in temperature and/or precipitation. The overall increase in CO 2 assimilation rate ( 13 C proxy) and enhanced C accumulation ( 14 C proxy) are consistent with warmer and wetter conditions currently generating higher growth rates than at any time in the past three millennia, with the decline in Δ perhaps compensated by a longer growing season. © 2012 Blackwell Publishing Ltd.

  9. Using short-term evidence to predict six-month outcomes in clinical trials of signs and symptoms in rheumatoid arthritis.

    PubMed

    Nixon, Richard M; Bansback, Nick; Stevens, John W; Brennan, Alan; Madan, Jason

    2009-01-01

    A model is presented to generate a distribution for the probability of an ACR response at six months for a new treatment for rheumatoid arthritis given evidence from a one- or three-month clinical trial. The model is based on published evidence from 11 randomized controlled trials on existing treatments. A hierarchical logistic regression model is used to find the relationship between the proportion of patients achieving ACR20 and ACR50 at one and three months and the proportion at six months. The model is assessed by Bayesian predictive P-values that demonstrate that the model fits the data well. The model can be used to predict the number of patients with an ACR response for proposed six-month clinical trials given data from clinical trials of one or three months duration. Copyright 2008 John Wiley & Sons, Ltd.

  10. Identifying the effective evidence sources to use in developing Clinical Guidelines for Acute Stroke Management: lived experiences of the search specialist and project manager.

    PubMed

    Parkhill, Anne; Hill, Kelvin

    2009-03-01

    The Australian National Stroke Foundation appointed a search specialist to find the best available evidence for the second edition of its Clinical Guidelines for Acute Stroke Management. To identify the relative effectiveness of differing evidence sources for the guideline update. We searched and reviewed references from five valid evidence sources for clinical and economic questions: (i) electronic databases; (ii) reference lists of relevant systematic reviews, guidelines, and/or primary studies; (iii) table of contents of a number of key journals for the last 6 months; (iv) internet/grey literature; and (v) experts. Reference sources were recorded, quantified, and analysed. In the clinical portion of the guidelines document, there was a greater use of previous knowledge and sources other than electronic databases for evidence, while there was a greater use of electronic databases for the economic section. The results confirmed that searchers need to be aware of the context and range of sources for evidence searches. For best available evidence, searchers cannot rely solely on electronic databases and need to encompass many different media and sources.

  11. Strengthening organizations to implement evidence-based clinical practices.

    PubMed

    VanDeusen Lukas, Carol; Engle, Ryann L; Holmes, Sally K; Parker, Victoria A; Petzel, Robert A; Nealon Seibert, Marjorie; Shwartz, Michael; Sullivan, Jennifer L

    2010-01-01

    Despite recognition that implementation of evidence-based clinical practices (EBPs) usually depends on the structure and processes of the larger health care organizational context, the dynamics of implementation are not well understood. This project's aim was to deepen that understanding by implementing and evaluating an organizational model hypothesized to strengthen the ability of health care organizations to facilitate EBPs. CONCEPTUAL MODEL: The model posits that implementation of EBPs will be enhanced through the presence of three interacting components: active leadership commitment to quality, robust clinical process redesign incorporating EBPs into routine operations, and use of management structures and processes to support and align redesign. In a mixed-methods longitudinal comparative case study design, seven medical centers in one network in the Department of Veterans Affairs participated in an intervention to implement the organizational model over 3 years. The network was selected randomly from three interested in using the model. The target EBP was hand-hygiene compliance. Measures included ratings of implementation fidelity, observed hand-hygiene compliance, and factors affecting model implementation drawn from interviews. Analyses support the hypothesis that greater fidelity to the organizational model was associated with higher compliance with hand-hygiene guidelines. High-fidelity sites showed larger effect sizes for improvement in hand-hygiene compliance than lower-fidelity sites. Adherence to the organizational model was in turn affected by factors in three categories: urgency to improve, organizational environment, and improvement climate. Implementation of EBPs, particularly those that cut across multiple processes of care, is a complex process with many possibilities for failure. The results provide the basis for a refined understanding of relationships among components of the organizational model and factors in the organizational context

  12. A survey of evidence users about the information need of acupuncture clinical evidence.

    PubMed

    Shi, Xiue; Wang, Xiaoqin; Liu, Yali; Li, Xiuxia; Wei, Dang; Zhao, Xu; Gu, Jing; Yang, Kehu

    2016-11-10

    The PRISMA statement was rarely used in the field of acupuncture, possibly because of knowledge gaps and the lack of items tailored for characteristics of acupuncture. And with an increasing number of systematic reviews in acupuncture, it is necessary to develop an extension of PRISMA for acupuncture. And this study was the first step of our project, of which the aim was to investigate the need for information of clinical evidence on acupuncture from the perspectives of evidence users. We designed a questionnaire based on a pilot survey and a literature review of acupuncture systematic review or meta-analysis(SR/MA). Participants from five cities (Lanzhou, Chengdu, Shanghai, Nanjing and Beijing) representing the different regions of China, including clinicians, researchers and postgraduates in their second year of Master studies or higher level, were surveyed. A total of 269 questionnaires were collected in 18 hospitals, medical universities and research agencies, and 251 (93 %) with complete data were used for analysis. The average age of respondents was 33 years (SD 8.959, range 25-58) with male 43 % and female 57 %. Most respondents had less than 5 years of working experience on acupuncture, and read only one to five articles per month. Electronic databases, search engines and academic conferences were the most common sources for obtaining information. Fifty-six percent of the respondents expressed low satisfaction of the completeness of information from the literature. The eight items proposed for acupuncture SR/MAs received all high scores, and five of the items scored higher than eight on a scale zero to ten. The differences for the scores of most items between postgraduates and non-postgraduates were not statistically significant. The majority of the respondents were not very satisfied with the information provided in acupuncture SRs. Most of the items proposed in this questionnaire received high scores, and opinions from postgraduates and non

  13. Evidence-Based Practice for Children with Speech Sound Disorders: Part 2 Application to Clinical Practice

    ERIC Educational Resources Information Center

    Baker, Elise; McLeod, Sharynne

    2011-01-01

    Purpose: This article provides both a tutorial and a clinical example of how speech-language pathologists (SLPs) can conduct evidence-based practice (EBP) when working with children with speech sound disorders (SSDs). It is a companion paper to the narrative review of 134 intervention studies for children who have an SSD (Baker & McLeod, 2011).…

  14. Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives.

    PubMed

    Sugianto, Tiffanie Daisy; Chan, Hak-Kim

    2016-01-01

    Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive, suppurative lung disease characterized by permanent dilatation of bronchial subdivisions, which further causes accumulation of sputum and bacterial infections. The advent of inhaled antibiotics over the past two decades has been expected to effectively attenuate the problem of chronic bacterial infections in CF and NCFB subjects with higher, local drug concentrations and minimal systemic side effects. This review summarizes and evaluates current clinical evidence of efficacy and adverse effects of inhaled antibiotics in NCFB, as well as ongoing preclinical and clinical studies, followed by a discussion of issues and challenges in clinical practice and drug delivery strategies, together with future research directions. The evidence base of the clinical efficacy of inhaled antibiotics in NCFB is limited and the degrees of reported clinical benefits have been modest and conflicting. Challenges surrounding inhaled antibiotics application and development include the lack of knowledge of disease factors and optimum management strategies, unreceptive lung pathophysiology and the lack of factors that support compliance and tolerability. Nonetheless, research continues to give birth to new clinical findings and novel formulations such as combination antibiotics and sustained-release formulations, which add great value to the development of efficacious, safe and convenient inhalable antibiotics of the future.

  15. Integrating evidence based medicine into undergraduate medical education: combining online instruction with clinical clerkships.

    PubMed

    Aronoff, Stephen C; Evans, Barry; Fleece, David; Lyons, Paul; Kaplan, Lawrence; Rojas, Roberto

    2010-07-01

    Incorporation of evidence based medicine into the undergraduate curriculum varies from school to school. The purpose of this study was to determine if an online course in evidence based medicine run concurrently with the clinical clerkships in the 3rd year of undergraduate medical education provided effective instruction in evidence based medicine (EBM). During the first 18 weeks of the 3rd year, students completed 6 online, didactic modules. Over the next 24 weeks, students developed questions independently from patients seen during clerkships and then retrieved and appraised relevant evidence. Online, faculty mentors reviewed student assignments submitted throughout the course to monitor progress. Mastery of the skills of EBM was assessed prior to and at the conclusion of the course using the Fresno test of competency. Paired data were available from 139 students. Postcourse test scores (M= 77.7; 95% CI = 59-96.4) were significantly higher than precourse scores (M= 66.6; 95% CI = 46.5-86.7), p< .001. Paired evaluations demonstrated an average improvement of 11.1 +/- 20.0 points. All of the students submitted 4 independently derived questions and successfully retrieved and appraised evidence. Medical students successfully acquired and independently applied EBM skills following extended, online, faculty mentored instruction. This method of instruction provided uniform instruction across geographic sites and medical specialties and permitted efficient use of faculty time.

  16. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.

    PubMed

    Arentz, Susan; Abbott, Jason Anthony; Smith, Caroline Anne; Bensoussan, Alan

    2014-12-18

    Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions. We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism. A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin

  17. Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS

    PubMed Central

    Trias, Emiliano; Ibarburu, Sofía; Barreto-Núñez, Romina; Varela, Valentina; Moura, Ivan C.; Hermine, Olivier

    2017-01-01

    Evidence indicates that neuroinflammation contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease leading to progressive muscular paralysis. However, it remains elusive whether inflammatory cells can interact with degenerating distal motor axons, influencing the progressive denervation of neuromuscular junctions (NMJs). By analyzing the muscle extensor digitorum longus (EDL) following paralysis onset in the SOD1G93A rat model, we have observed a massive infiltration and degranulation of mast cells, starting after paralysis onset and correlating with progressive NMJ denervation. Remarkably, mast cells accumulated around degenerating motor axons and NMJs, and were also associated with macrophages. Mast cell accumulation and degranulation in paralytic EDL muscle was prevented by systemic treatment over 15 days with masitinib, a tyrosine kinase inhibitor currently in clinical trials for ALS exhibiting pharmacological activity affecting mast cells and microglia. Masitinib-induced mast cell reduction resulted in a 35% decrease in NMJ denervation and reduced motor deficits as compared with vehicle-treated rats. Masitinib also normalized macrophage infiltration, as well as regressive changes in Schwann cells and capillary networks observed in advanced paralysis. These findings provide evidence for mast cell contribution to distal axonopathy and paralysis progression in ALS, a mechanism that can be therapeutically targeted by masitinib. PMID:29046475

  18. Enhancement of cognitive and neural functions through complex reasoning training: evidence from normal and clinical populations

    PubMed Central

    Chapman, Sandra B.; Mudar, Raksha A.

    2014-01-01

    Public awareness of cognitive health is fairly recent compared to physical health. Growing evidence suggests that cognitive training offers promise in augmenting cognitive brain performance in normal and clinical populations. Targeting higher-order cognitive functions, such as reasoning in particular, may promote generalized cognitive changes necessary for supporting the complexities of daily life. This data-driven perspective highlights cognitive and brain changes measured in randomized clinical trials that trained gist reasoning strategies in populations ranging from teenagers to healthy older adults, individuals with brain injury to those at-risk for Alzheimer's disease. The evidence presented across studies support the potential for Gist reasoning training to strengthen cognitive performance in trained and untrained domains and to engage more efficient communication across widespread neural networks that support higher-order cognition. The meaningful benefits of Gist training provide compelling motivation to examine optimal dose for sustained benefits as well as to explore additive benefits of meditation, physical exercise, and/or improved sleep in future studies. PMID:24808834

  19. Multiple anatomy optimization of accumulated dose

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

  20. Accumulation of atmospheric sulfur in some Costa Rican soils

    USGS Publications Warehouse

    Bern, Carleton R.; Townsend, Alan R.

    2013-01-01

    Sulfur is one of the macronutrient elements whose sources to terrestrial ecosystems should shift from dominance by rock-weathering to atmospheric deposition as soils and underlying substrate undergo progressive weathering and leaching. However, the nature and timing of this transition is not well known. We investigated sources of sulfur to tropical rain forests growing on basalt-derived soils in the Osa Peninsula region of Costa Rica. Sulfur sources were examined using stable isotope ratios (δ34S) and compared to chemical indices of soil development. The most weathered soils, and the forests they supported, are dominated by atmospheric sulfur, while a less weathered soil type contains both rock-derived and atmospheric sulfur. Patterns of increasing δ34S with increasing soil sulfur concentration across the landscape suggest atmospheric sulfur is accumulating, and little rock-derived sulfur has been retained. Soil sulfur, minus adsorbed sulfate, is correlated with carbon and nitrogen, implying that sulfur accumulation occurs as plants and microbes incorporate sulfur into organic matter. Only the lower depth increments of the more weathered soils contained significant adsorbed sulfate. The evidence suggests a pattern of soil development in which sulfur-bearing minerals in rock, such as sulfides, weather early relative to other minerals, and the released sulfate is leached away. Sulfur added via atmospheric deposition is retained as organic matter accumulates in the soil profile. Adsorbed sulfate accumulates later, driven by changes in soil chemistry and mineralogy. These aspects of sulfur behavior during pedogenesis in this environment may hasten the transition to dominance by atmospheric sources.

  1. Distinct spatiotemporal accumulation of N-truncated and full-length amyloid-β42 in Alzheimer's disease.

    PubMed

    Shinohara, Mitsuru; Koga, Shunsuke; Konno, Takuya; Nix, Jeremy; Shinohara, Motoko; Aoki, Naoya; Das, Pritam; Parisi, Joseph E; Petersen, Ronald C; Rosenberry, Terrone L; Dickson, Dennis W; Bu, Guojun

    2017-12-01

    Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease. To this end, the amounts of amyloid-β species and other proteins related to amyloid-β metabolism or Alzheimer's disease were quantified by enzyme-linked immunosorbent assays (ELISA) or theoretically calculated in 12 brain regions, including neocortical, limbic and subcortical areas from Alzheimer's disease cases (n = 19), neurologically normal elderly without amyloid-β accumulation (normal ageing, n = 13), and neurologically normal elderly with cortical amyloid-β accumulation (pathological ageing, n = 15). We observed that N-terminally truncated amyloid-β42 and full-length amyloid-β42 accumulations distributed differently across disease stages and brain areas, while N-terminally truncated amyloid-β40 and full-length amyloid-β40 accumulation showed an almost identical distribution pattern. Cortical N-terminally truncated amyloid-β42 accumulation was increased in Alzheimer's disease compared to pathological ageing, whereas cortical full-length amyloid-β42 accumulation was comparable between Alzheimer's disease and pathological ageing. Moreover, N-terminally truncated amyloid-β42 were more likely to accumulate more in specific brain areas, especially some limbic areas, while full-length amyloid-β42 tended to accumulate more in several neocortical areas, including frontal cortices. Immunoprecipitation followed by mass spectrometry analysis showed that several N-terminally truncated amyloid-β42 species, represented by pyroglutamylated amyloid-β11

  2. [Evidence-based medicine: the art of applying scientific knowledge in clinical practice].

    PubMed

    Lopes, A A

    2000-01-01

    This article was written with the objective of describing the concept of Evidence Based Medicine (EBM) and the competences required for its practice. EBM should be viewed as an integration of clinical experience with the ability to analyze and rationally apply the scientific information while taking care of patients. The application of methods and strategies to enhance the scientific background of the physician while taking into account the humanitarian values of the medical profession should contribute to improve the quality of the medical care that is offered in Brazil. The Medical Schools and Associations may play important roles in the promotion of EBM.

  3. An evidence-based approach to assessing surgical versus clinical diagnosis of symptomatic endometriosis.

    PubMed

    Taylor, Hugh S; Adamson, G David; Diamond, Michael P; Goldstein, Steven R; Horne, Andrew W; Missmer, Stacey A; Snabes, Michael C; Surrey, Eric; Taylor, Robert N

    2018-05-05

    Challenges intrinsic to the accurate diagnosis of endometriosis contribute to an extended delay between the onset of symptoms and clinical confirmation. Intraoperative visualization, preferably with histologic verification, is considered by many professional organizations to be the gold standard by which endometriosis is diagnosed. Clinical diagnosis of symptomatic endometriosis via patient history, physical examination, and noninvasive tests, though more easily executed, is generally viewed as less accurate than surgical diagnosis. Technological advances and increased understanding of the pathophysiology of endometriosis warrant continuing reevaluation of the standard method for diagnosing symptomatic disease. A review of the published literature was therefore performed with the goal of comparing the accuracy of clinical diagnostic measures with that of surgical diagnosis. The current body of evidence suggests that clinical diagnosis of symptomatic endometriosis is more reliable than previously recognized and that surgical diagnosis has limitations that could be underappreciated. Regardless of the methodology used, women with suspected symptomatic endometriosis would be well served by a diagnostic paradigm that is reliable, conveys minimal risk of under- or over-diagnosis, lessens the time from symptom development to diagnosis, and guides the appropriate use of medical and surgical management strategies. © 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

  4. Evidence-based Practices Addressed in Community-based Children’s Mental Health Clinical Supervision

    PubMed Central

    Accurso, Erin C.; Taylor, Robin M.; Garland, Ann F.

    2013-01-01

    Context Clinical supervision is the principal method of training for psychotherapeutic practice, however there is virtually no research on supervision practice in community settings. Of particular interest is the role supervision might play in facilitating implementation of evidence-based (EB) care in routine care settings. Objective This study examines the format and functions of clinical supervision sessions in routine care, as well as the extent to which supervision addresses psychotherapeutic practice elements common to EB care for children with disruptive behavior problems, who represent the majority of patients served in publicly-funded routine care settings. Methods Supervisors (n=7) and supervisees (n=12) from four publicly-funded community-based child mental health clinics reported on 130 supervision sessions. Results Supervision sessions were primarily individual in-person meetings lasting one hour. The most common functions included case conceptualization and therapy interventions. Coverage of practice elements common to EB treatments was brief. Discussion Despite the fact that most children presenting to public mental health services are referred for disruptive behavior problems, supervision sessions are infrequently focused on practice elements consistent with EB treatments for this population. Supervision is a promising avenue through which training in EB practices could be supported to improve the quality of care for children in community-based “usual care” clinics. PMID:24761163

  5. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    He, Qin; Sha, Sha; Sun, Lei

    The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and inducedmore » hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD. -- Highlights: •Liraglutide reduces lipid accumulation in hepatic steatosis both in vivo and in vitro. •Autophagy was involved in relieving effects of liraglutide on hepatic steatosis. •AMPK/mTOR pathway was involved in liraglutide-induced autophagy.« less

  6. Meta-Analyses and Orthodontic Evidence-Based Clinical Practice in the 21st Century

    PubMed Central

    Papadopoulos, Moschos A.

    2010-01-01

    Introduction: Aim of this systematic review was to assess the orthodontic related issues which currently provide the best evidence as documented by meta-analyses, by critically evaluating and discussing the methodology used in these studies. Material and Methods: Several electronic databases were searched and handsearching was also performed in order to identify the corresponding meta-analyses investigating orthodontic related subjects. In total, 197 studies were retrieved initially. After applying specific inclusion and exclusion criteria, 27 articles were identified as meta-analyses treating orthodontic-related subjects. Results: Many of these 27 papers presented sufficient quality and followed appropriate meta-analytic approaches to quantitatively synthesize data and presented adequately supported evidence. However, the methodology used in some of them presented weaknesses, limitations or deficiencies. Consequently, the topics in orthodontics which currently provide the best evidence, include some issues related to Class II or Class III treatment, treatment of transverse problems, external apical root resorption, dental anomalies, such as congenital missing teeth and tooth transposition, frequency of severe occlusal problems, nickel hypersensitivity, obstructive sleep apnea syndrome, and computer-assisted learning in orthodontic education. Conclusions: Only a few orthodontic related issues have been so far investigated by means of MAs. In addition, for some of these issues investigated in the corresponding MAs no definite conclusions could be drawn, due to significant methodological deficiencies of these studies. According to this investigation, it can be concluded that at the begin of the 21st century there is evidence for only a few orthodontic related issues as documented by meta-analyses, and more well-conducted high quality research studies are needed to produce strong evidence in order to support evidence-based clinical practice in orthodontics. PMID

  7. Diagnosing dehydration? Blend evidence with clinical observations.

    PubMed

    Armstrong, Lawrence E; Kavouras, Stavros A; Walsh, Neil P; Roberts, William O

    2016-11-01

    The purpose of the review is to provide recommendations to improve clinical decision-making based on the strengths and weaknesses of commonly used hydration biomarkers and clinical assessment methods. There is widespread consensus regarding treatment, but not the diagnosis of dehydration. Even though it is generally accepted that a proper clinical diagnosis of dehydration can only be made biochemically rather than relying upon clinical signs and symptoms, no gold standard biochemical hydration index exists. Other than clinical biomarkers in blood (i.e., osmolality and blood urea nitrogen/creatinine) and in urine (i.e., osmolality and specific gravity), blood pressure assessment and clinical symptoms in the eye (i.e., tear production and palpitating pressure) and the mouth (i.e., thirst and mucous wetness) can provide important information for diagnosing dehydration. We conclude that clinical observations based on a combination of history, physical examination, laboratory values, and clinician experience remain the best approach to the diagnosis of dehydration.

  8. A commentary on the associations among 'food addiction', binge eating disorder, and obesity: Overlapping conditions with idiosyncratic clinical features.

    PubMed

    Davis, Caroline

    2017-08-01

    This commentary discusses the evidence linking patterns of compulsive overeating, such as binge eating and grazing, with a putative psychopathological condition known commonly as 'food addiction'. It also addresses their distinctiveness as independent - albeit overlapping - clinical entities. Discussions focus largely on their respective clinical features and neuropsychobiological associations. Despite semantic issues about the appropriateness of the food-addiction label, there is accumulating evidence that some vulnerable individuals display addictive symptoms in relation to their consumption of certain highly rewarding foods. It is also argued in this paper that despite a positive relationship between obesity and addictive tendencies towards food, it is over-inclusive to model obesity as an addiction disorder, especially given the multi-faceted etiology and current pervasiveness of weight gain worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Only One Third of Tehran's Physicians are Familiar with 'Evidence-Based Clinical Guidelines'.

    PubMed

    Mounesan, Leila; Nedjat, Saharnaz; Majdzadeh, Reza; Rashidian, Arash; Gholami, Jaleh

    2013-03-01

    Clinical guidelines have increasingly been used as tools for applying new knowledge and research findings. Although, efforts have been made to produce clinical guidelines in Iran, it is not clear whether they have been used by physicians and what factors are associated with them?. Four hundred and forty three practicing physicians in Tehran were selected from private clinics through weighted random sampling. The data collection tool was a questionnaire on familiarity and attitude toward clinical guidelines. The descriptive and analytical findings were analyzed with t-tests, Chi(2), logistic and linear multivariate regression by SPSS, version 16. 31.8% of physicians were familiar with clinical guidelines. Based on the logistic regression model physicians' familiarity with clinical guidelines was positively and significantly associated with 'working experience in a health service delivery point' OR = 2.13 (95% CI, 1.17-3.90), 'familiarity with therapeutic protocols' OR = 2.09 (95% CI, 1.22-3.57) and 'holding a specialty degree' OR = 2.51 (95% CI, 1.24-5.07). The mean overall attitude scores in the 'usefulness', 'reliability', and 'problems and barriers' domains were, respectively, 78.9 (SD = 16.5), 78.9 (SD = 19.7) and 50.4 (SD = 15.9) out of a total of 100 scores in each domain. No significant association was observed between attitude domains and other independent variables using multivariate linear regression. Little familiarity with clinical guidelines may represent weakness in of production and distribution of domestic evidence. Although, physicians considered guidelines as useful and reliable tools, but problems such as difficult access to guidelines and lack of facilities to apply them were stated as well.

  10. Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) in the Asia Pacific region (Round Table Forum).

    PubMed

    Su, Tin Tin; Bulgiba, Awang M; Sampatanukul, Pichet; Sastroasmoro, Sudigdo; Chang, Peter; Tharyan, Prathap; Lin, Vivian; Wong, Yut Lin

    2013-01-01

    Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) have become increasingly important in an era of rising costs, patient safety concerns and evidence-based health care. CE and EBM research in the Asia Pacific region have grown significantly. However, there are three main challenges such as linking evidence to practice and policy; developing a strong collaborative network; and a need for resources and technical expertise to produce evidence. The Cochrane Collaboration is a possible solution to resolve above challenges identified, particularly the challenge of transforming evidence to practice. In addition, training can be carried out to enhance technical expertise in the region and there is also the promising potential that collaborations could extend beyond systematic reviews. To improve the adoption of evidence-based health policy, selection of the best evidence for the right audience and focusing on the relevant issues through appropriate methodology are essential. Information on effectiveness and cost effectiveness needs to be highlighted for policy makers. The way forward to strengthen research and capacity building is to establish the Asia Pacific Consortium for CE and EBM. The consortium would help to create mutually rewarding scientific research and collaborations that will augur well for advances in CE and EBM. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Sex, Gender, and Pain: A Review of Recent Clinical and Experimental Findings

    PubMed Central

    Fillingim, Roger B.; King, Christopher D.; Ribeiro-Dasilva, Margarete C.; Rahim-Williams, Bridgett; Riley, Joseph L.

    2009-01-01

    Sex-related influences on pain and analgesia have become a topic of tremendous scientific and clinical interest, especially in the last 10 to 15 years. Members of our research group published reviews of this literature more than a decade ago, and the intervening time period has witnessed robust growth in research regarding sex, gender, and pain. Therefore, it seems timely to revisit this literature. Abundant evidence from recent epidemiologic studies clearly demonstrates that women are at substantially greater risk for many clinical pain conditions, and there is some suggestion that postoperative and procedural pain may be more severe among women than men. Consistent with our previous reviews, current human findings regarding sex differences in experimental pain indicate greater pain sensitivity among females compared with males for most pain modalities, including more recently implemented clinically relevant pain models such as temporal summation of pain and intramuscular injection of algesic substances. The evidence regarding sex differences in laboratory measures of endogenous pain modulation is mixed, as are findings from studies using functional brain imaging to ascertain sex differences in pain-related cerebral activation. Also inconsistent are findings regarding sex differences in responses to pharmacologic and non-pharmacologic pain treatments. The article concludes with a discussion of potential biopsychosocial mechanisms that may underlie sex differences in pain, and considerations for future research are discussed. Perspective This article reviews the recent literature regarding sex, gender, and pain. The growing body of evidence that has accumulated in the past 10 to 15 years continues to indicate substantial sex differences in clinical and experimental pain responses, and some evidence suggests that pain treatment responses may differ for women versus men. PMID:19411059

  12. [Evidence-based management of medical disposable materials].

    PubMed

    Yang, Hai

    2009-03-01

    Evidence-based management of medical disposable materials pays attention to collect evidence comprehensively and systematically, accumulate and create evidence through its own work and also evaluate evidence strictly. This can be used as a function to guide out job. Medical disposable materials evidence system contains product register qualification, product quality certification, supplier's behavior, internal and external communication evidence. Managers can find different ways in creating and using evidence referring to specific inside and outside condition. Evidence-based management can help accelerating the development of management of medical disposable materials from traditional experience pattern to a systematic and scientific pattern. It also has the very important meaning to improve medical quality, control the unreasonable growth of medical expense and make purchase and supply chain be more efficient.

  13. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

    PubMed

    Esposito, Susanna; Soto-Martinez, Manuel E; Feleszko, Wojciech; Jones, Marcus H; Shen, Kun-Ling; Schaad, Urs B

    2018-06-01

    To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic. An established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.

  14. Progressive nonfluent aphasia: a rare clinical subtype of FTLD-TDP in Japan.

    PubMed

    Aoki, Naoya; Tsuchiya, Kuniaki; Kobayashi, Zen; Arai, Tetsuaki; Togo, Takashi; Miyazaki, Hiroshi; Kondo, Hiromi; Ishizu, Hideki; Uchikado, Hirotake; Katsuse, Omi; Hirayasu, Yoshio; Akiyama, Haruhiko

    2012-06-01

    Progressive nonfluent aphasia (PNFA) is a clinical subtype of frontotemporal lobar degeneration (FTLD). FTLD with tau accumulation (FTLD-tau) and FTLD with TDP-43 accumulation (FTLD-TDP) both cause PNFA. We reviewed clinical records of 29 FTLD-TDP cases in the brain archive of our institute and found only one case of PNFA. The patient was an 81-year-old male at death. There was no family history of dementia or aphasia. He presented with slow, labored and nonfluent speech at age 75. Behavioral abnormality and movement disorders were absent. MRI at age 76 demonstrated atrophy of the perisylvian regions, including the inferior frontal gyrus, insular gyrus and superior temporal gyrus. The atrophy was more severe in the left hemisphere than the right. On post mortem examinations, neuronal loss was evident in these regions as well as in the substantia nigra. There were abundant TDP-43-immunoreactive neuronal cytoplasmic inclusions and round or irregular-shaped structures in the affected cerebral cortices. A few dystrophic neurites and neuronal intranuclear inclusions were also seen. FTLD-TDP showing PNFA seems to be rare but does exist in Japan, similar to that in other countries. © 2011 Japanese Society of Neuropathology.

  15. Status quo, issues, and challenges for acupuncture research evidence: an overview of clinical and fundamental studies.

    PubMed

    Cai, Yujia; Shen, Jiantong; Zhong, Dake; Li, Youping; Wu, Taixiang

    2012-02-01

    To systematically review the status quo, issues, and challenges from home and abroad for acupuncture research evidence, in order to identify global acupuncture research datum lines and policy-making evidence for future research direction. To carry out computed searching through the Cochrane Library, MEDLINE, CNKI, SCI, WHO-ICTRP, and Chinese Clinical Trials Registry (ChiCTR) (up to January, 2010) for acupuncture-related secondary studies (systematic reviews and meta-analysis), animal randomized controlled trials (RCTs), published human RCTs (fundamental research with the human body or human body specimens as subjects), and registered on-going clinical trials (regardless of subject recruiting), and to analyze yearly publishing trends and research hotspots on subject headings for secondary studies and published and registered RCTs. (1) 63.7% of acupuncture clinical RCTs were published in the Cochrane Central Register of Controlled Trials (CENTRAL), while RCTs published in MEDLINE, SCI, and CNKI each accounted for a third of all acupuncture fundamental RCTs. Publishing trends of acupuncture clinical RCTs indicated three periods - a period of slow growth before 1998, a period of gradual growth between 1999 and 2005, and a period of rapid growth after 2005. While few fundamental acupuncture RCTs were published before 2004, the period after 2005 demonstrated an increasing trend, but did not exhibit the same rapid growth as with clinical RCTs. Publication of Cochrane systematic reviews (CSRs) exhibited a time-dependent effect with acupuncture clinical RCTs, a trend that became more pronounced as time passed, while time intervals between CSR and acupuncture clinical RCT publications decreased. (2) Nine SRs were published in China, accounting for 30% of the global total of 29, while China's 68 RCTs accounted for 21% of global RCTs. Among five CSRs affirming the effects of acupuncture, only one contained four RCTs from China, which accounted for 10% of all RCTs included in

  16. Weighing Clinical Evidence Using Patient Preferences: An Application of Probabilistic Multi-Criteria Decision Analysis.

    PubMed

    Broekhuizen, Henk; IJzerman, Maarten J; Hauber, A Brett; Groothuis-Oudshoorn, Catharina G M

    2017-03-01

    The need for patient engagement has been recognized by regulatory agencies, but there is no consensus about how to operationalize this. One approach is the formal elicitation and use of patient preferences for weighing clinical outcomes. The aim of this study was to demonstrate how patient preferences can be used to weigh clinical outcomes when both preferences and clinical outcomes are uncertain by applying a probabilistic value-based multi-criteria decision analysis (MCDA) method. Probability distributions were used to model random variation and parameter uncertainty in preferences, and parameter uncertainty in clinical outcomes. The posterior value distributions and rank probabilities for each treatment were obtained using Monte-Carlo simulations. The probability of achieving the first rank is the probability that a treatment represents the highest value to patients. We illustrated our methodology for a simplified case on six HIV treatments. Preferences were modeled with normal distributions and clinical outcomes were modeled with beta distributions. The treatment value distributions showed the rank order of treatments according to patients and illustrate the remaining decision uncertainty. This study demonstrated how patient preference data can be used to weigh clinical evidence using MCDA. The model takes into account uncertainty in preferences and clinical outcomes. The model can support decision makers during the aggregation step of the MCDA process and provides a first step toward preference-based personalized medicine, yet requires further testing regarding its appropriate use in real-world settings.

  17. Caring for women living with HIV: gaps in the evidence

    PubMed Central

    Loutfy, Mona R; Sherr, Lorraine; Sonnenberg-Schwan, Ulrike; Walmsley, Sharon L; Johnson, Margaret; d'Arminio Monforte, Antonella

    2013-01-01

    Introduction In the management of HIV, women and men generally undergo the same treatment pathway, with gender differences being given limited consideration. This is in spite of accumulating evidence that there are a number of potential differences between women and men which may affect response to treatment, pharmacokinetics, toxicities and coping. There are also notable psychological, behavioural, social and structural factors that may have a unique impact on women living with HIV (WLWH). Despite our increasing knowledge of HIV and advances in treatment, there are significant gaps in the data relating specifically to women. One of the factors contributing to this situation is the under-representation of women in all aspects of HIV clinical research. Furthermore, there are clinical issues unique to women, including gynaecologic and breast diseases, menopause-related factors, contraception and other topics related to women's and sexual health. Methods Using scoping review methodology, articles from the literature from 1980 to 2012 were identified using appropriate MeSH headings reflecting the clinical status of WLWH, particularly in the areas of clinical management, sexual health, emotional wellbeing and treatment access. Titles and abstracts were scanned to determine whether they were relevant to non-reproductive health in WLWH, and papers meeting inclusion criteria were reviewed. Results This review summarizes our current knowledge of the clinical status of WLWH, particularly in the areas of clinical management, sexual health, emotional wellbeing and treatment access. It suggests that there are a number of gender differences in disease and treatment outcomes, and distinct women-specific issues, such as menopause and co-morbidities, that pose significant challenges to the care of WLWH. Conclusions Based on a review of this evidence, outstanding questions and areas where further studies are required to determine gender differences in the efficacy and safety of

  18. Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited.

    PubMed

    Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor

    2013-12-01

    Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

  19. Clarifying Evidence-Based Medicine in Educational and Therapeutic Experiences of Clinical Faculty Members: A Qualitative Study in Iran

    PubMed Central

    Safari, Yahya

    2015-01-01

    Introduction: Although evidence-based medicine has been a significant part of recent research efforts to reform the health care system, it requires an assessment of real life community and patient. The present study strives to clarify the concept of evidence-based medicine in educational and therapeutic experiences of clinical faculty members of Kermanshah University of Medical Sciences (2014). Materials and Methods: It was a qualitative study of phenomenology. The population consists of 12 clinical faculty members of Kermanshah University Medical Sciences. Sampling was carried out using a purposeful method. Sample volume was determined using adequacy of samples’ law. Data gathering occurred through semi-structured interviews. Collaizzi pattern was employed for data interpretation concurrent with data gathering. Results: interpreting the data, three main themes were extracted. They include: 1. Unawareness and disuse (unaware of the concept, disuse, referral to colleagues, experiment prescription) 2. Conscious or unconscious use (using journals and scientific websites, aware of the process). 3. Beliefs (belief or disbelief in necessity). Conclusion: It sounds essential to change the behavior of clinical faculty members from passive to active with respect to employing evidence-based medicine as well as to alter negative attitudes into positive ones. In so doing, systematic training program aiming at behavior changing is necessary. Also, providing dissent facilities and infrastructures and removing barriers to the use of EBM can be effective. PMID:26153205

  20. Clarifying Evidence-Based Medicine in Educational and Therapeutic Experiences of Clinical Faculty Members: A Qualitative Study in Iran.

    PubMed

    Safari, Yahya

    2015-03-26

    Although evidence-based medicine has been a significant part of recent research efforts to reform the health care system, it requires an assessment of real life community and patient. The present study strives to clarify the concept of evidence-based medicine in educational and therapeutic experiences of clinical faculty members of Kermanshah University of Medical Sciences (2014). It was a qualitative study of phenomenology. The population consists of 12 clinical faculty members of Kermanshah University Medical Sciences. Sampling was carried out using a purposeful method. Sample volume was determined using adequacy of samples' law. Data gathering occurred through semi-structured interviews. Collaizzi pattern was employed for data interpretation concurrent with data gathering. interpreting the data, three main themes were extracted. They include: 1. Unawareness and disuse (unaware of the concept, disuse, referral to colleagues, experiment prescription) 2. Conscious or unconscious use (using journals and scientific websites, aware of the process). 3. Beliefs (belief or disbelief in necessity). It sounds essential to change the behavior of clinical faculty members from passive to active with respect to employing evidence-based medicine as well as to alter negative attitudes into positive ones. In so doing, systematic training program aiming at behavior changing is necessary. Also, providing dissent facilities and infrastructures and removing barriers to the use of EBM can be effective.

  1. Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

    PubMed

    Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

    2017-12-01

    Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

  2. Ecological strategies of Al-accumulating and non-accumulating functional groups from the cerrado sensu stricto.

    PubMed

    Souza, Marcelo C de; Bueno, Paula C P; Morellato, Leonor P C; Habermann, Gustavo

    2015-01-01

    The cerrado's flora comprises aluminum-(Al) accumulating and non-accumulating plants, which coexist on acidic and Al-rich soils with low fertility. Despite their existence, the ecological importance or biological strategies of these functional groups have been little explored. We evaluated the leaf flushing patterns of both groups throughout a year; leaf concentrations of N, P, K, Ca, Mg, S, Al, total flavonoids and polyphenols; as well as the specific leaf area (SLA) on young and mature leaves within and between the groups. In Al-accumulating plants, leaf flushed throughout the year, mainly in May and September; for non-accumulating plants, leaf flushing peaked at the dry-wet seasons transition. However, these behaviors could not be associated with strategies for building up concentrations of defense compounds in leaves of any functional groups. Al-accumulating plants showed low leaf nutrient concentrations, while non-accumulating plants accumulated more macronutrients and produced leaves with high SLA since the juvenile leaf phase. This demonstrates that the increase in SLA is slower in Al-accumulating plants that are likely to achieve SLA values comparable to the rest of the plant community only in the wet season, when sunlight capture is important for the growth of new branches.

  3. Clinical evidence on titanium-zirconium dental implants: a systematic review and meta-analysis.

    PubMed

    Altuna, P; Lucas-Taulé, E; Gargallo-Albiol, J; Figueras-Álvarez, O; Hernández-Alfaro, F; Nart, J

    2016-07-01

    The use of titanium implants is well documented and they have high survival and success rates. However, when used as reduced-diameter implants, the risk of fracture is increased. Narrow diameter implants (NDIs) of titanium-zirconium (Ti-Zr) alloy have recently been developed (Roxolid; Institut Straumann AG). Ti-Zr alloys (two highly biocompatible materials) demonstrate higher tensile strength than commercially pure titanium. The aim of this systematic review was to summarize the existing clinical evidence on dental NDIs made from Ti-Zr. A systematic literature search was performed using the Medline database to find relevant articles on clinical studies published in the English language up to December 2014. Nine clinical studies using Ti-Zr implants were identified. Overall, 607 patients received 922 implants. The mean marginal bone loss was 0.36±0.06mm after 1 year and 0.41±0.09mm after 2 years. The follow-up period ranged from 3 to 36 months. Mean survival and success rates were 98.4% and 97.8% at 1 year after implant placement and 97.7% and 97.3% at 2 years. Narrow diameter Ti-Zr dental implants show survival and success rates comparable to regular diameter titanium implants (>95%) in the short term. Long-term follow-up clinical data are needed to confirm the excellent clinical performance of these implants. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences.

    PubMed

    Javaheri, Shahrokh; Barbe, Ferran; Campos-Rodriguez, Francisco; Dempsey, Jerome A; Khayat, Rami; Javaheri, Sogol; Malhotra, Atul; Martinez-Garcia, Miguel A; Mehra, Reena; Pack, Allan I; Polotsky, Vsevolod Y; Redline, Susan; Somers, Virend K

    2017-02-21

    Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke. Several discoveries in the pathogenesis, along with developments in the treatment of sleep apnea, have accumulated in recent years. In this review, we discuss the mechanisms of sleep apnea, the evidence that addresses the links between sleep apnea and cardiovascular disease, and research that has addressed the effect of sleep apnea treatment on cardiovascular disease and clinical endpoints. Finally, we review the recent development in sleep apnea treatment options, with special consideration of treating patients with heart disease. Future directions for selective areas are suggested. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Experimental evidence of zone-center optical phonon softening by accumulating holes in thin Ge

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kabuyanagi, Shoichi; Nishimura, Tomonori; Yajima, Takeaki

    2016-01-15

    We discuss the impact of free carriers on the zone-center optical phonon frequency in germanium (Ge). By taking advantage of the Ge-on-insulator structure, we measured the Raman spectroscopy by applying back-gate bias. Phonon softening by accumulating holes in Ge film was clearly observed. This fact strongly suggests that the phonon softening in heavily-doped Ge is mainly attributed to the free carrier effect rather than the dopant atom counterpart. Furthermore, we propose that the free carrier effect on phonon softening is simply understandable from the viewpoint of covalent bonding modification by free carriers.

  6. An exactly solvable, spatial model of mutation accumulation in cancer

    NASA Astrophysics Data System (ADS)

    Paterson, Chay; Nowak, Martin A.; Waclaw, Bartlomiej

    2016-12-01

    One of the hallmarks of cancer is the accumulation of driver mutations which increase the net reproductive rate of cancer cells and allow them to spread. This process has been studied in mathematical models of well mixed populations, and in computer simulations of three-dimensional spatial models. But the computational complexity of these more realistic, spatial models makes it difficult to simulate realistically large and clinically detectable solid tumours. Here we describe an exactly solvable mathematical model of a tumour featuring replication, mutation and local migration of cancer cells. The model predicts a quasi-exponential growth of large tumours, even if different fragments of the tumour grow sub-exponentially due to nutrient and space limitations. The model reproduces clinically observed tumour growth times using biologically plausible rates for cell birth, death, and migration rates. We also show that the expected number of accumulated driver mutations increases exponentially in time if the average fitness gain per driver is constant, and that it reaches a plateau if the gains decrease over time. We discuss the realism of the underlying assumptions and possible extensions of the model.

  7. A Knowledge-Modeling Approach to Integrate Multiple Clinical Practice Guidelines to Provide Evidence-Based Clinical Decision Support for Managing Comorbid Conditions.

    PubMed

    Abidi, Samina

    2017-10-26

    Clinical management of comorbidities is a challenge, especially in a clinical decision support setting, as it requires the safe and efficient reconciliation of multiple disease-specific clinical procedures to formulate a comorbid therapeutic plan that is both effective and safe for the patient. In this paper we pursue the integration of multiple disease-specific Clinical Practice Guidelines (CPG) in order to manage co-morbidities within a computerized Clinical Decision Support System (CDSS). We present a CPG integration framework-termed as COMET (Comorbidity Ontological Modeling & ExecuTion) that manifests a knowledge management approach to model, computerize and integrate multiple CPG to yield a comorbid CPG knowledge model that upon execution can provide evidence-based recommendations for handling comorbid patients. COMET exploits semantic web technologies to achieve (a) CPG knowledge synthesis to translate a paper-based CPG to disease-specific clinical pathways (CP) that include specialized co-morbidity management procedures based on input from domain experts; (b) CPG knowledge modeling to computerize the disease-specific CP using a Comorbidity CPG ontology; (c) CPG knowledge integration by aligning multiple ontologically-modeled CP to develop a unified comorbid CPG knowledge model; and (e) CPG knowledge execution using reasoning engines to derive CPG-mediated recommendations for managing patients with comorbidities. We present a web-accessible COMET CDSS that provides family physicians with CPG-mediated comorbidity decision support to manage Atrial Fibrillation and Chronic Heart Failure. We present our qualitative and quantitative analysis of the knowledge content and usability of COMET CDSS.

  8. Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

    PubMed

    Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

    2015-01-01

    Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

  9. Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis.

    PubMed

    Silva, Liliana J G; Martins, Margarida C; Pereira, André M P T; Meisel, Leonor M; Gonzalez-Rey, Maria; Bebianno, Maria João; Lino, Celeste M; Pena, Angelina

    2016-06-01

    Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI) antidepressant, is among the most prescribed pharmaceutical active substances worldwide. This study aimed to assess its accumulation and metabolization in the mussel Mytillus galloprovincialis, considered an excellent sentinel species for traditional and emerging pollutants. Mussels were collected from Ria Formosa Lagoon, Portugal, and exposed to a nominal concentration of fluoxetine (75 ng L(-1)) for 15 days. Approximately 1 g of whole mussel soft tissues was extracted with acetonitrile:formic acid, loaded into an Oasis MCX cartridge, and fluoxetine analysed by liquid chromatography with tandem mass spectrometry (LC-MSn). After 3 days of exposure, fluoxetine was accumulated in 70% of the samples, with a mean of 2.53 ng g(-1) dry weight (d.w.) and norfluoxetine was only detected in one sample (10%), at 3.06 ng g(-1) d.w. After 7 days of exposure, the accumulation of fluoxetine and norfluoxetine increased up to 80 and 50% respectively, and their mean accumulated levels in mussel tissues were up to 4.43 and 2.85 ng g(-1) d.w., respectively. By the end of the exposure period (15 days), both compounds were detected in 100% of the samples (mean of 9.31 and 11.65 ng g(-1) d.w., respectively). Statistical analysis revealed significant accumulation differences between the 3rd and 15th day of exposure for fluoxetine, and between the 3rd and 7th against the 15th day of exposure for norfluoxetine. These results suggest that the fluoxetine accumulated in mussel tissues is likely to be metabolised into norfluoxetine with the increase of the time of exposure, giving evidence that at these realistic environmental concentrations, toxic effects of fluoxetine in mussel tissues may occur. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effect of Hypergravity and Phytohormones on Isoflavonoid Accumulation in Soybean ( Glycine max. L.) Callus

    NASA Astrophysics Data System (ADS)

    Downey, Peter J.; Levine, Lanfang H.; Musgrave, Mary E.; McKeon-Bennett, Michelle; Moane, Siobhán

    2013-02-01

    The objective of this study was to explore the potential interaction between gravity and growth hormones on isoflavonoid accumulation. Soybean callus ( Glycine max (L.) Merr. cv. `Acme') was grown in the dark for 16 days at 22 °C in a growth medium supplemented with four different combinations of phytohormones and subjected to 4- g and 8- g forces simulated in a centrifuge and 1- g in an adjacent stationary control. Isoflavonoid aglycones and their glycoside concentrations (daidzein, genistein, daidzin, 6″-O-malonyl-7-O-glucosyl daidzein, genistin, 6″-O-malonyl-7-O-glucosyl genistein) were determined in the resulting tissues. Although gravity had no significant impact on callus growth, increasing gravity reduced isoflavonoid accumulation in three out of the four phytohormone-supplemented culture media. The ratio of the auxin naphthalene acetic acid (NAA) to the cytokinin benzylaminopurine (BAP) was found to have profound effect on both callus growth and isoflavonoid accumulation. The cytokinin BAP promoted callus tissue growth, but reduced callus isoflavonoid suggesting the isoflavonoid accumulation was not keeping pace with the cell growth in the elevated concentration of BAP. On the other hand, NAA had little or no effect on callus growth, but greatly enhanced isoflavonoid accumulation. Interactive effects of gravity and hormone on isoflavonoid accumulation were evident and its implication to the mechanism by which gravity exerts the effect on plant secondary metabolites is discussed.

  11. Continuous and Episodic Modern Sediment Accumulation on Monterey Fan: Evidence from Ddt, 137Cs and Excess 210Pb

    NASA Astrophysics Data System (ADS)

    Gwiazda, R.; Paull, C. K.; Alexander, C. R.; Ussler, W.

    2012-12-01

    The mode and magnitude of fine-grained sediment accumulation on the Monterey Fan off the California central coast was investigated using pesticide concentrations and radioactive tracer profiles in sediment cores. DDT is a man-made pesticide that was used extensively in central California between 1945 and 1970. As such, its presence in marine sediments is a telltale sign of a modern sedimentation age. DDT and its metabolites, DDE and DDD, (collectively referred to as DDTr) were measured in fifty-five ~20cm-long sediment cores collected from the surface of the Monterey Fan up to 250 km to the south and 210 km to the west of the Monterey Canyon head, and in four transects across the Monterey Canyon channel at maximum water depths of 3160, 3380, 3580, and 3880 meters. Profiles of excess 210Pb (210Pbxs) and 137Cs were measured in 5 cores from the Fan to estimate recent sedimentation rates. Detectable levels of DDTr were observed in all but one of these cores, with DDTr concentrations characteristically highest at the surface and decreasing with depth. The area-normalized and depth-integrated DDTr content measured in all the cores in the Fan and in the deepest two channel transects was geographically fairly homogenous, with no statistical relationship between DDTr inventory and distance from the main channel crossing the Fan. The total sediment mass deposited on the Fan over the last 60 years, inferred from the total inventory of DDTr present in the area surveyed, is consistent with the amount of sediment delivered by the Salinas River over the same time period. 210Pbxs activities are fairly homogeneous within an uppermost layer of variable thickness (4.6-8cm) and decrease exponentially below it, but these exponential decreases are often interrupted by horizons with constant or increased 210Pbxs activity. Moreover, the coexistence of variable DDTr concentrations with homogeneous 210Pbxs activities in the top sediment indicates that the uniformity of 210Pbxs is not due

  12. Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover.

    PubMed

    Zhu, Xiongwei; Castellani, Rudy J; Moreira, Paula I; Aliev, Gjumrakch; Shenk, Justin C; Siedlak, Sandra L; Harris, Peggy L R; Fujioka, Hisashi; Sayre, Lawrence M; Szweda, Pamela A; Szweda, Luke I; Smith, Mark A; Perry, George

    2012-02-01

    Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently bind amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated in intimate association with the pathological lesions of Alzheimer disease (AD), suggesting that oxidative stress is a major component of AD pathogenesis. Some HNE-protein products result in protein crosslinking through a fluorescent compound similar to lipofuscin, linking lipid peroxidation and the lipofuscin accumulation that commonly occurs in post-mitotic cells such as neurons. In this study, brain tissue from AD and control patients was examined by immunocytochemistry and immunoelectron microscopy for evidence of HNE-crosslinking modifications of the type that should accumulate in the lipofuscin pathway. Strong labeling of granulovacuolar degeneration (GVD) and Hirano bodies was noted but lipofuscin did not contain this specific HNE-fluorophore. These findings directly implicate lipid crosslinking peroxidation products as accumulating not in the lesions or the lipofuscin pathways, but instead in a distinct pathway, GVD, that accumulates cytosolic proteins. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Evidence-Based Medicine: Rhinoplasty.

    PubMed

    Lee, Matthew K; Most, Sam P

    2015-08-01

    Evidence-based medicine has become increasingly prominent in the climate of modern day healthcare. The practice of evidence-based medicine involves the integration of the best available evidence with clinical experience and expertise to help guide clinical decision-making. The essential tenets of evidence-based medicine can be applied to both functional and aesthetic rhinoplasty. Current outcome measures in functional and aesthetic rhinoplasty, including objective, subjective, and clinician-reported measures, is summarized and the current data is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Synthesizing Quantitative Evidence for Evidence-based Nursing: Systematic Review.

    PubMed

    Oh, Eui Geum

    2016-06-01

    As evidence-based practice has become an important issue in healthcare settings, the educational needs for knowledge and skills for the generation and utilization of healthcare evidence are increasing. Systematic review (SR), a way of evidence generation, is a synthesis of primary scientific evidence, which summarizes the best evidence on a specific clinical question using a transparent, a priori protocol driven approach. SR methodology requires a critical appraisal of primary studies, data extraction in a reliable and repeatable way, and examination for validity of the results. SRs are considered hierarchically as the highest form of evidence as they are a systematic search, identification, and summarization of the available evidence to answer a focused clinical question with particular attention to the methodological quality of studies or the credibility of opinion and text. The purpose of this paper is to introduce an overview of the fundamental knowledge, principals and processes in SR. The focus of this paper is on SR especially for the synthesis of quantitative data from primary research studies that examines the effectiveness of healthcare interventions. To activate evidence-based nursing care in various healthcare settings, the best and available scientific evidence are essential components. This paper will include some examples to promote understandings. Copyright © 2016. Published by Elsevier B.V.

  15. Is the Information about a Test Important? Applying the Methods of Evidence-Based Medicine to the Clinical Examination of Swallowing

    ERIC Educational Resources Information Center

    Rosenbek, John C.; McCullough, Gary H.; Wertz, Robert T.

    2004-01-01

    A hotly debated topic in oropharyngeal dysphagia is the Clinical Swallowing Examination's (CSE) importance in clinical practice. That debate can profit from the application of evidence-based medicine's (EBM) principles and procedures. These can guide both appropriate data collection and interpretation as will be demonstrated in the present report.…

  16. Classification of clinically useful sentences in clinical evidence resources.

    PubMed

    Morid, Mohammad Amin; Fiszman, Marcelo; Raja, Kalpana; Jonnalagadda, Siddhartha R; Del Fiol, Guilherme

    2016-04-01

    Most patient care questions raised by clinicians can be answered by online clinical knowledge resources. However, important barriers still challenge the use of these resources at the point of care. To design and assess a method for extracting clinically useful sentences from synthesized online clinical resources that represent the most clinically useful information for directly answering clinicians' information needs. We developed a Kernel-based Bayesian Network classification model based on different domain-specific feature types extracted from sentences in a gold standard composed of 18 UpToDate documents. These features included UMLS concepts and their semantic groups, semantic predications extracted by SemRep, patient population identified by a pattern-based natural language processing (NLP) algorithm, and cue words extracted by a feature selection technique. Algorithm performance was measured in terms of precision, recall, and F-measure. The feature-rich approach yielded an F-measure of 74% versus 37% for a feature co-occurrence method (p<0.001). Excluding predication, population, semantic concept or text-based features reduced the F-measure to 62%, 66%, 58% and 69% respectively (p<0.01). The classifier applied to Medline sentences reached an F-measure of 73%, which is equivalent to the performance of the classifier on UpToDate sentences (p=0.62). The feature-rich approach significantly outperformed general baseline methods. This approach significantly outperformed classifiers based on a single type of feature. Different types of semantic features provided a unique contribution to overall classification performance. The classifier's model and features used for UpToDate generalized well to Medline abstracts. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Do firms underinvest in long-term research? Evidence from cancer clinical trials.

    PubMed

    Budish, Eric; Roin, Benjamin N; Williams, Heidi

    2015-07-01

    We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials - and hence, project durations - are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design.

  18. iPadagogy 101: Using Clinical ORthopedic Exam (C.O.R.E.) to Facilitate Evidence-Based Practice in the Orthopaedic Evaluation Classroom

    ERIC Educational Resources Information Center

    Hamson-Utley, J. Jordan; Stiller-Ostrowski, Jennifer L.

    2013-01-01

    Evidence-based practice (EBP) and educational technology have become fundamental skills within athletic training programs. The objective of this article is to share experiences implementing clinical orthopaedic evaluation applications ("apps") that can be integrated into classroom and clinical education to enhance students' proficiency…

  19. A lee-side eddy and its influence on snow accumulation

    NASA Astrophysics Data System (ADS)

    Gerber, Franziska; Mott, Rebecca; Hoch, Sebastian W.; Lehning, Michael

    2016-04-01

    Knowledge of changes in seasonal mountain snow water resources is essential for e.g. hydropower companies. To successfully predict these changes a fundamental understanding of precipitation patterns and their changes in mountainous terrain is needed. Both, snow accumulation and ablation need to be investigated to make precise predictions of the amount of water stored in seasonal snow cover. Only if the processes governing snow accumulation and ablation are understood with sufficient quantitative accuracy, the evolution of snow water resources under a changing climate can be addressed. Additionally, knowledge of detailed snow accumulation patterns is essential to assess avalanche danger. In alpine terrain, snow accumulation is strongly dependent on the local wind field. Based on the concept of preferential deposition, reduced snow accumulation is expected on the upper windward slope of a mountain due to updrafts, while enhanced snow accumulation should occur through blocking at the windward foot or due to flow separation on the leeward side. However, the understanding of these processes is mainly based on numerical simulations, as they are hard to measure. A LiDAR (Light Detection And Ranging) campaign was conducted in October 2015 in the Dischma valley (Davos, CH) to investigate the local flow field in the lee of the Sattelhorn during a one-day snowfall event. The flow field was monitored using a plane position indicator (PPI) scan at 25/28° and a range height indicator (RHI) scan across the Sattelhorn. Additionally, snow height change measurements on the leeward side of the Sattelhorn were performed by terrestrial laser scanning (TLS). Analyses of the flow field in the framework of preferential deposition are in agreement with the concept of flow separation and preferred snow deposition on leeward slopes. A very persistent eddy that formed over the leeward slope of the Sattelhorn detached from the main flow became evident from the retrievals of the RHI scans. An

  20. 150,000 years of loess accumulation in central Alaska

    NASA Astrophysics Data System (ADS)

    Jensen, Britta J. L.; Evans, Michael E.; Froese, Duane G.; Kravchinsky, Vadim A.

    2016-03-01

    The Halfway House site in interior Alaska is arguably the most studied loess deposit in northwestern North America. The site contains a complex paleomagnetic and paleoenvironmental record, but has lacked the robust chronologic control that would allow its full potential to be exploited. Detailed reexamination of stratigraphy, paleomagnetics and tephrostratigraphy reveals a relatively complete marine isotope stage (MIS) 6 to Holocene record constrained by the Old Crow (124 ± 10 ka), VT (106 ± 10 ka), Sheep Creek-Klondike (ca. 80 ka), Dominion Creek (77 ± 8 ka) and Dawson (ca. 30.2 cal ka BP) tephras. We show two well-developed paleosols formed during Marine Isotope Stages (MIS) 5e and 5a, while MIS 5c and 5b are either poorly represented or absent. The new tephrostratigraphy presented here is the most complete one to date for the late Pleistocene and indicates MIS 5 sediments are more common than previously recognized. A magnetic excursion within the sediments is identified as the post-Blake excursion (94.1 ± 7.8 ka), providing independent age control and adding to the increasing body of evidence that Alaskan loess is a detailed recorder of variations of the Earth's magnetic field over time. A high-resolution magnetic susceptibility profile placed into this new chronostratigraphic framework supports the hypothesis that wind-intensity is the main variable controlling fluctuations in susceptibility. Correlation of the susceptibility record to global marine δ18O records is complicated by highly variable accumulation rates. We find the lowest rates of accumulation during peak warm and cold stages, while abrupt increases are associated with periods of transition between marine isotope (sub)stages. Building on previous accumulation models for Alaska, surface roughness is likely a leading variable controlling loess accumulation rates during transitions and peak cold periods, but the negligible accumulation during MIS 5e and 5a suggests that loess production was

  1. Evidence-based policy as reflexive practice. What can we learn from evidence-based medicine?

    PubMed

    Bal, Roland

    2017-04-01

    The call for evidence-based policy is often accompanied by rather uncritical references to the success of evidence-based medicine, leading to often unsuccessful translation attempts. In this paper, I reflect on the practice of evidence-based medicine in an attempt to sketch a more productive approach to translating evidence into the practice of policy making. Discussing three episodes in the history of evidence-based medicine - clinical trials, and the production and use of clinical guidelines - I conclude that the success of evidence-based medicine is based on the creation of reflexive practices in which evidence and practice can be combined productively. In the conclusion, I discuss the prospects of such a practice for evidence-based policy.

  2. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine.

    PubMed

    Green, Robert C; Goddard, Katrina A B; Jarvik, Gail P; Amendola, Laura M; Appelbaum, Paul S; Berg, Jonathan S; Bernhardt, Barbara A; Biesecker, Leslie G; Biswas, Sawona; Blout, Carrie L; Bowling, Kevin M; Brothers, Kyle B; Burke, Wylie; Caga-Anan, Charlisse F; Chinnaiyan, Arul M; Chung, Wendy K; Clayton, Ellen W; Cooper, Gregory M; East, Kelly; Evans, James P; Fullerton, Stephanie M; Garraway, Levi A; Garrett, Jeremy R; Gray, Stacy W; Henderson, Gail E; Hindorff, Lucia A; Holm, Ingrid A; Lewis, Michelle Huckaby; Hutter, Carolyn M; Janne, Pasi A; Joffe, Steven; Kaufman, David; Knoppers, Bartha M; Koenig, Barbara A; Krantz, Ian D; Manolio, Teri A; McCullough, Laurence; McEwen, Jean; McGuire, Amy; Muzny, Donna; Myers, Richard M; Nickerson, Deborah A; Ou, Jeffrey; Parsons, Donald W; Petersen, Gloria M; Plon, Sharon E; Rehm, Heidi L; Roberts, J Scott; Robinson, Dan; Salama, Joseph S; Scollon, Sarah; Sharp, Richard R; Shirts, Brian; Spinner, Nancy B; Tabor, Holly K; Tarczy-Hornoch, Peter; Veenstra, David L; Wagle, Nikhil; Weck, Karen; Wilfond, Benjamin S; Wilhelmsen, Kirk; Wolf, Susan M; Wynn, Julia; Yu, Joon-Ho

    2016-06-02

    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine. Copyright © 2016 American Society of Human Genetics. All rights reserved.

  3. Simple non-invasive assessment of advanced glycation endproduct accumulation.

    PubMed

    Meerwaldt, R; Graaff, R; Oomen, P H N; Links, T P; Jager, J J; Alderson, N L; Thorpe, S R; Baynes, J W; Gans, R O B; Smit, A J

    2004-07-01

    The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, paccumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.

  4. Research Gaps in Practice Guidelines for Acute Postoperative Pain Management in Adults: Findings From a Review of the Evidence for an American Pain Society Clinical Practice Guideline.

    PubMed

    Gordon, Debra B; de Leon-Casasola, Oscar A; Wu, Christopher L; Sluka, Kathleen A; Brennan, Timothy J; Chou, Roger

    2016-02-01

    Acute postoperative pain is a common clinical condition that, when poorly controlled, can result in a number of significant negative consequences. The American Pain Society commissioned an evidence-based guideline on the management of postoperative pain to promote evidence-based, safe, and effective perioperative pain management. An interdisciplinary panel developed 31 key questions and inclusion criteria to guide the evidence review. Investigators reviewed 6556 abstracts from multiple electronic databases up to November 2012, an updated evidence review to October 2014, and key references suggested by expert reviewers. More than 800 primary studies not included in a systematic review and 107 systematic reviews were included. Despite a large body of evidence, a number of critical research gaps were identified where only low-quality or insufficient evidence was found to help guide clinical practice recommendations. This report identifies evidence gaps including optimal methods and timing of perioperative patient education, nonpharmacological modalities, combinations of analgesic techniques, monitoring of patient response to treatment, techniques for neuraxial and regional analgesia, and organizational care delivery models. Recommendations to help guide the design of future perioperative studies are offered. Acute postoperative pain is a common clinical condition requiring an evidence-based, planned, and multimodal approach. Despite the plethora of published evidence, much of it is weak and key questions remain unanswered. Researchers are encouraged to work together to produce strong evidence to help guide clinical decisions in perioperative pain management. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Use of Decision Models in the Development of Evidence-Based Clinical Preventive Services Recommendations: Methods of the U.S. Preventive Services Task Force.

    PubMed

    Owens, Douglas K; Whitlock, Evelyn P; Henderson, Jillian; Pignone, Michael P; Krist, Alex H; Bibbins-Domingo, Kirsten; Curry, Susan J; Davidson, Karina W; Ebell, Mark; Gillman, Matthew W; Grossman, David C; Kemper, Alex R; Kurth, Ann E; Maciosek, Michael; Siu, Albert L; LeFevre, Michael L

    2016-10-04

    The U.S. Preventive Services Task Force (USPSTF) develops evidence-based recommendations about preventive care based on comprehensive systematic reviews of the best available evidence. Decision models provide a complementary, quantitative approach to support the USPSTF as it deliberates about the evidence and develops recommendations for clinical and policy use. This article describes the rationale for using modeling, an approach to selecting topics for modeling, and how modeling may inform recommendations about clinical preventive services. Decision modeling is useful when clinical questions remain about how to target an empirically established clinical preventive service at the individual or program level or when complex determinations of magnitude of net benefit, overall or among important subpopulations, are required. Before deciding whether to use decision modeling, the USPSTF assesses whether the benefits and harms of the preventive service have been established empirically, assesses whether there are key issues about applicability or implementation that modeling could address, and then defines the decision problem and key questions to address through modeling. Decision analyses conducted for the USPSTF are expected to follow best practices for modeling. For chosen topics, the USPSTF assesses the strengths and limitations of the systematically reviewed evidence and the modeling analyses and integrates the results of each to make preventive service recommendations.

  6. How Many Dystonias? Clinical Evidence.

    PubMed

    Albanese, Alberto

    2017-01-01

    Literary reports on dystonia date back to post-Medieval times. Medical reports are instead more recent. We review here the early descriptions and the historical establishment of a consensus on the clinical phenomenology and the diagnostic features of dystonia syndromes. Lumping and splitting exercises have characterized this area of knowledge, and it remains largely unclear how many dystonia types we are to count. This review describes the history leading to recognize that focal dystonia syndromes are a coherent clinical set encompassing cranial dystonia (including blepharospasm), oromandibular dystonia, spasmodic torticollis, truncal dystonia, writer's cramp, and other occupational dystonias. Papers describing features of dystonia and diagnostic criteria are critically analyzed and put into historical perspective. Issues and inconsistencies in this lumping effort are discussed, and the currently unmet needs are critically reviewed.

  7. Evidence-based neurosurgery

    PubMed Central

    Esene, Ignatius N.; Baeesa, Saleh S.; Ammar, Ahmed

    2016-01-01

    Medical evidence is obtainable from approaches, which might be descriptive, analytic and integrative and ranked into levels of evidence, graded according to quality and summarized into strengths of recommendation. Sources of evidence range from expert opinions through well-randomized control trials to meta-analyses. The conscientious, explicit, and judicious use of current best evidence in making decisions related to the care of individual patients defines the concept of evidence-based neurosurgery (EBN). We reviewed reference books of clinical epidemiology, evidence-based practice and other previously related articles addressing principles of evidence-based practice in neurosurgery. Based on existing theories and models and our cumulative years of experience and expertise conducting research and promoting EBN, we have synthesized and presented a holistic overview of the concept of EBN. We have also underscored the importance of clinical research and its relationship to EBN. Useful electronic resources are provided. The concept of critical appraisal is introduced. PMID:27356649

  8. Systematic clinical evidence review of NASHA (Durolane hyaluronic acid) for the treatment of knee osteoarthritis.

    PubMed

    Leighton, Ross; Fitzpatrick, Jane; Smith, Helen; Crandall, Daniela; Flannery, Carl R; Conrozier, Thierry

    2018-01-01

    Pain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells). This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs). The available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment. Treatment with NASHA is an effective and safe single

  9. β-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.

    PubMed

    Hayflick, Susan J; Kruer, Michael C; Gregory, Allison; Haack, Tobias B; Kurian, Manju A; Houlden, Henry H; Anderson, James; Boddaert, Nathalie; Sanford, Lynn; Harik, Sami I; Dandu, Vasuki H; Nardocci, Nardo; Zorzi, Giovanna; Dunaway, Todd; Tarnopolsky, Mark; Skinner, Steven; Holden, Kenton R; Frucht, Steven; Hanspal, Era; Schrander-Stumpel, Connie; Mignot, Cyril; Héron, Delphine; Saunders, Dawn E; Kaminska, Margaret; Lin, Jean-Pierre; Lascelles, Karine; Cuno, Stephan M; Meyer, Esther; Garavaglia, Barbara; Bhatia, Kailash; de Silva, Rajith; Crisp, Sarah; Lunt, Peter; Carey, Martyn; Hardy, John; Meitinger, Thomas; Prokisch, Holger; Hogarth, Penelope

    2013-06-01

    Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

  10. The Role of Three-Dimensional Scaffolds in Treating Long Bone Defects: Evidence from Preclinical and Clinical Literature-A Systematic Review.

    PubMed

    Roffi, Alice; Krishnakumar, Gopal Shankar; Gostynska, Natalia; Kon, Elizaveta; Candrian, Christian; Filardo, Giuseppe

    2017-01-01

    Long bone defects represent a clinical challenge. Bone tissue engineering (BTE) has been developed to overcome problems associated with conventional methods. The aim of this study was to assess the BTE strategies available in preclinical and clinical settings and the current evidence supporting this approach. A systematic literature screening was performed on PubMed database, searching for both preclinical (only on large animals) and clinical studies. The following string was used: "(Scaffold OR Implant) AND (Long bone defect OR segmental bone defect OR large bone defect OR bone loss defect)." The search retrieved a total of 1573 articles: 51 preclinical and 4 clinical studies were included. The great amount of preclinical papers published over the past few years showed promising findings in terms of radiological and histological evidence. Unfortunately, this in vivo situation is not reflected by a corresponding clinical impact, with few published papers, highly heterogeneous and with small patient populations. Several aspects should be further investigated to translate positive preclinical findings into clinical protocols: the identification of the best biomaterial, with both biological and biomechanical suitable properties, and the selection of the best choice between cells, GFs, or their combination through standardized models to be validated by randomized trials.

  11. Relationship of Basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration.

    PubMed

    Sarks, Shirley; Cherepanoff, Svetlana; Killingsworth, Murray; Sarks, John

    2007-03-01

    To correlate basal laminar deposit (BLamD) and membranous debris, including basal linear deposit (BLinD), with the evolution of early age-related macular degeneration (AMD). A clinicopathologic collection of 132 eyes with a continuous layer of BLamD was reviewed. The thickness and type of BLamD and the sites of membranous debris deposition were correlated with the clinical progression of the disease. Two types of BLamD, termed early and late, were identified based on light microscopic appearance by using the picro-Mallory stain. The progressive accumulation of late type BLamD correlated well with increasing BLamD thickness, advancing RPE degeneration, poorer vision, increasing age, and clinically evident pigment changes. Membranous debris initially accumulated diffusely as BLinD, most eyes with BLinD and early BLamD remaining funduscopically normal. However, membranous debris also formed focal collections as basal mounds internal to the RPE basement membrane and as soft drusen external to the basement membrane. Eyes in which membranous debris remained confined to basal mounds belonged to older patients with poorer vision, whereas patients with soft drusen were younger and had better vision. The presence of BLinD and early BLamD define threshold AMD, which manifests clinically as a normal fundus. Although late BLamD correlates most closely with clinical pigment abnormalities, it is the quantity and sites of membranous debris accumulation that appear to determine whether the disease develops pigment changes only or follows the alternative pathway of soft drusen formation with its attendant greater risk of choroidal neovascularization (CNV).

  12. Clinical study assessing the photosensitizer accumulation and light penetration for esophageal cancer prior to treatment by PDT

    NASA Astrophysics Data System (ADS)

    Bargo, Paulo R.; Jacques, Steven L.

    2001-07-01

    The FDA has approved PDT using Photofrin for certain esophageal and lung cancers, specifying an approved prescription of administered drug (mg/kg body weight) and administered light (J/linear cm of cylindrical fiber). This paper describes our development of a multi-optical fiber catheter for endoscopic use which documents the drug accumulated in the target tissues and the light penetration into the target tissues. The catheter uses reflectance to specify the light penetration depth and uses reflectance- corrected fluorescence to document drug accumulation. The goal is to document the variation in drug and light received by patients who are administered the FDA-approved prescription.

  13. Accumulated Dose in Liver Stereotactic Body Radiotherapy: Positioning, Breathing, and Deformation Effects

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Velec, Michael, E-mail: michael.velec@rmp.uhn.on.ca; Institute of Medical Science, University of Toronto, Toronto, ON; Moseley, Joanne L.

    2012-07-15

    Purpose: To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic body radiotherapy (SBRT) and investigate their geometric causes. Methods and Materials: Thirty previously treated liver cancer patients were retrospectively evaluated. Stereotactic body radiotherapy was planned on the static exhale CT for 27-60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning four-dimensional (4D) CT (predicted breathing dose) and also over each fraction's respiratory-correlated cone-beam CT (accumulated treatment dose). The contribution of different geometric errors to changes between themore » accumulated and predicted breathing dose were quantified. Results: Twenty-one patients (70%) had accumulated dose deviations relative to the planned static prescription dose >5%, ranging from -15% to 5% in tumors and -42% to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4D CT-predicted dose, which were similar in magnitude. Thirty-two tissues in these 16 patients had deviations >5% relative to the 4D CT-predicted dose, and residual setup errors (n = 17) were most often the largest cause of the deviations, followed by deformations (n = 8) and breathing variations (n = 7). Conclusion: The majority of patients had accumulated dose deviations >5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in more than half the patients, commonly owing to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose escalation, adaptive SBRT, and aid in correlation with clinical outcomes.« less

  14. Cardioprotective effects of cocoa: clinical evidence from randomized clinical intervention trials in humans.

    PubMed

    Arranz, Sara; Valderas-Martinez, Palmira; Chiva-Blanch, Gemma; Casas, Rosa; Urpi-Sarda, Mireia; Lamuela-Raventos, Rosa M; Estruch, Ramon

    2013-06-01

    Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These products contain higher amounts of flavonoids than other polyphenol-rich foods. However, the bioavailability of these compounds depends on other food constituents and their interactions with the food matrix. Many epidemiological and clinical intervention trials have concluded that the ingestion of flavonoids reduces the risk factors of developing cardiovascular disease. This review summarizes the new findings regarding the effects of cocoa and chocolate consumption on cardiovascular risk factors. The mechanisms involved in the cardioprotective effects of cocoa flavonoids include reduction of oxidative stress, inhibition of low-density lipoproteins oxidation and platelet aggregation, vasodilatation of blood vessels, inhibition of the adherence of monocytes to vascular endothelium, promotion of fibrinolysis, and immunomodulatory and anti-inflammatory activity. Scientific evidence supports a cause and effect relationship between consumption of cocoa flavonoids and the maintenance of normal endothelium-dependent vasodilation, which contributes to normal blood flow. However, larger randomized trials are required to definitively establish the impact of cocoa and cocoa products consumption on hard cardiovascular outcomes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. A Clinical Translation of the Article Titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder".

    PubMed

    Shannon, Robin Adair

    2015-01-01

    The purpose of this article is to offer a clinical translation of a literature review titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder" by Ryberg (2015). The literature review was conducted to determine the strength of the research evidence regarding the effectiveness of the Early Start Denver Model in improving cognitive, language, and behavioral functioning of children with autism spectrum disorder. In an effort to narrow the gap between evidence and practice, this clinical translation will discuss the components of the literature review in terms of its rationale for and objectives, methods, results, and implications for evidence-based nursing practice. © The Author(s) 2015.

  16. Personalised Care Plan Management Utilizing Guideline-Driven Clinical Decision Support Systems.

    PubMed

    Laleci Erturkmen, Gokce Banu; Yuksel, Mustafa; Sarigul, Bunyamin; Lilja, Mikael; Chen, Rong; Arvanitis, Theodoros N

    2018-01-01

    Older age is associated with an increased accumulation of multiple chronic conditions. The clinical management of patients suffering from multiple chronic conditions is very complex, disconnected and time-consuming with the traditional care settings. Integrated care is a means to address the growing demand for improved patient experience and health outcomes of multimorbid and long-term care patients. Care planning is a prevalent approach of integrated care, where the aim is to deliver more personalized and targeted care creating shared care plans by clearly articulating the role of each provider and patient in the care process. In this paper, we present a method and corresponding implementation of a semi-automatic care plan management tool, integrated with clinical decision support services which can seamlessly access and assess the electronic health records (EHRs) of the patient in comparison with evidence based clinical guidelines to suggest personalized recommendations for goals and interventions to be added to the individualized care plans.

  17. Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1.

    PubMed

    Schmitt, Manfred; Mengele, Karin; Napieralski, Rudolf; Magdolen, Viktor; Reuning, Ute; Gkazepis, Apostolos; Sweep, Fred; Brünner, Nils; Foekens, John; Harbeck, Nadia

    2010-11-01

    The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.

  18. Recent advances in evidence-based psychiatry.

    PubMed

    Geddes, J; Carney, S

    2001-06-01

    There is increasing interest in the potential contribution of evidence-based medicine to clinical decision making in psychiatry. In this article, we describe some of the recent advances in evidence-based psychiatry and outline future challenges. Narrative review. The successful introduction of evidence-based practice into psychiatry requires the acquisition of new skills by clinicians. It is also important that policy statements that aim to be evidence-based, such as clinical practice guidelines, use rigorous methods to synthesize the primary evidence and do not overlook its limitations. One result of the systematic reviewing of evidence is the identification of important residual clinical uncertainties. Primary research can then be focused on these questions. For questions regarding therapy in psychiatry, it will be necessary to undertake some large, simple randomized trials. Making the best available evidence readily accessible in a clinical setting, however, remains a significant challenge. Collaboration between clinicians, researchers, policy-makers, and those involved in information technology is required to optimize the contribution of evidence-based medicine in psychiatry.

  19. Evidence-based practice.

    PubMed Central

    McKibbon, K A

    1998-01-01

    Evidence-based practice (EBP) is spreading in popularity in many health care disciplines. One of its main features is the reliance on the partnership among hard scientific evidence, clinical expertise, and individual patient needs and choices. Librarians play an important role in the spread of EBP because of the importance of identifying and retrieving appropriate literature from various sources for use in making health care decisions. This article gives an overview of how to search for therapy, diagnosis, etiology, and prognosis both for original studies and secondary publications such as systematic reviews, meta-analyses, and clinical practice guidelines. Understanding how this research is done, how it is indexed, and how to retrieve the clinical evidence are an important set of skills that librarians can provide for clinicians interested in EBP. PMID:9681176

  20. Evidence-based review of clinical outcomes of guideline-recommended pharmacotherapies for generalized anxiety disorder.

    PubMed

    Bereza, Basil G; Machado, Márcio; Ravindran, Arun V; Einarson, Thomas R

    2012-08-01

    To quantify the rates of clinical outcomes of Canadian Psychiatric Association (CPA) guideline-recommended pharmacotherapies for generalized anxiety disorder (GAD) by drug classification within each treatment line. Evidence from original research cited by the CPA was included. Pooled analyses, duplicates, and studies with nonextractable data were excluded. Response, remission, and baseline-endpoint or mean reductions scores of the Hamilton Anxiety Rating Scale (HARS) were extracted. The Cochrane Collaboration's computer program, Review Manager, version 5, with a random effects model, was used to pool results. A total of 50 articles were cited as evidence for managing GAD by the CPA. There was sufficient evidence of remission with first- or third-line agents to pool reported rates, and with agents from all 3 treatment lines to pool response rates and reduction in HARS scores. The mean range of effect size varied considerably from study to study within each treatment line. Comparison of pooled remission rates between first- and second-line agents was not possible. While the range of values by drug and drug class overlapped, the summary results for the probability of response and reduction in HARS scores was greater for first-line, compared with second-line, treatments. Drug components for third-line treatments were heterogeneous and produced mixed results. Despite the abundance of evidence in its totality presented in the CPA guidelines, there is inadequate evidence to formulate recommendations based on the pooled results from this study alone. However, such analysis provides an additional resource for clinicians to make more effective treatment decisions for individual patients with GAD.

  1. Review of toluene action: clinical evidence, animal studies and molecular targets

    PubMed Central

    Cruz, Silvia L.; Rivera-García, María Teresa; Woodward, John J.

    2014-01-01

    It has long been known that individuals will engage in voluntary inhalation of volatile solvents for their rewarding effects. However, research into the neurobiology of these agents has lagged behind that of more commonly used drugs of abuse such as psychostimulants, alcohol and nicotine. This imbalance has begun to shift in recent years as the serious effects of abused inhalants, especially among children and adolescents, on brain function and behavior have become appreciated and scientifically documented. In this review, we discuss the physicochemical and pharmacological properties of toluene, a representative member of a large class of organic solvents commonly used as inhalants. This is followed by a brief summary of the clinical and pre-clinical evidence showing that toluene and related solvents produce significant effects on brain structures and processes involved in the rewarding aspects of drugs. This is highlighted by tables highlighting toluene’s effect on behaviors (reward, motor effects, learning, etc.) and cellular proteins (e.g. voltage and ligand-gated ion channels) closely associated the actions of abused substances. These sections demonstrate not only the significant progress that has been made in understanding the neurobiological basis for solvent abuse but also reveal the challenges that remain in developing a coherent understanding of this often overlooked class of drugs of abuse. PMID:25360325

  2. Evidence flowers: An innovative, visual method of presenting "best evidence" summaries to health professional and lay audiences.

    PubMed

    Babatunde, O O; Tan, V; Jordan, J L; Dziedzic, K; Chew-Graham, C A; Jinks, C; Protheroe, J; van der Windt, D A

    2018-06-01

    Barriers to dissemination and engagement with evidence pose a threat to implementing evidence-based medicine. Understanding, retention, and recall can be enhanced by visual presentation of information. The aim of this exploratory research was to develop and evaluate the accessibility and acceptability of visual summaries for presenting evidence syntheses with multiple exposures or outcomes to professional and lay audiences. "Evidence flowers" were developed as a visual method of presenting data from 4 case scenarios: 2 complex evidence syntheses with multiple outcomes, Cochrane reviews, and clinical guidelines. Petals of evidence flowers were coloured according to the GRADE evidence rating system to display key findings and recommendations from the evidence summaries. Application of evidence flowers was observed during stakeholder workshops. Evaluation and feedback were conducted via questionnaires and informal interviews. Feedback from stakeholders on the evidence flowers collected from workshops, questionnaires, and interviews was encouraging and helpful for refining the design of the flowers. Comments were made on the content and design of the flowers, as well as the usability and potential for displaying different types of evidence. Evidence flowers are a novel and visually stimulating method for presenting research evidence from evidence syntheses with multiple exposures or outcomes, Cochrane reviews, and clinical guidelines. To promote access and engagement with research evidence, evidence flowers may be used in conjunction with other evidence synthesis products, such as (lay) summaries, evidence inventories, rapid reviews, and clinical guidelines. Additional research on potential adaptations and applications of the evidence flowers may further bridge the gap between research evidence and clinical practice. Copyright © 2018 John Wiley & Sons, Ltd.

  3. Implementation of Evidence-Based Practice in Relation to a Clinical Nursing Ladder System: A National Survey in Taiwan

    PubMed Central

    Weng, Yi-Hao; Chen, Chiehfeng; Kuo, Ken N; Yang, Chun-Yuh; Lo, Heng-Lien; Chen, Kee-Hsin; Chiu, Ya-Wen

    2015-01-01

    Background Although evidence-based practice (EBP) has been widely investigated, few studies have investigated its correlation with a clinical nursing ladder system. The current national study evaluates whether EBP implementation has been incorporated into the clinical ladder system. Methods A cross-sectional questionnaire survey was conducted nationwide of registered nurses among regional hospitals of Taiwan in January to April 2011. Subjects were categorized into beginning nurses (N1 and N2) and advanced nurses (N3 and N4) by the clinical ladder system. Multivariate logistic regression model was used to adjust for possible confounding demographic factors. Results Valid postal questionnaires were collected from 4,206 nurses, including 2,028 N1, 1,595 N2, 412 N3, and 171 N4 nurses. Advanced nurses were more aware of EBP than beginning nurses (p < 0.001; 90.7% vs. 78.0%). In addition, advanced nurses were more likely to hold positive beliefs about and attitudes toward EBP (p < 0.001) and possessed more sufficient knowledge of and skills in EBP (p < 0.001). Furthermore, they more often implemented EBP principles (p < 0.001) and accessed online evidence-based retrieval databases (p < 0.001). The most common motivation for using online databases was self-learning for advanced nurses and positional promotion for beginning nurses. Multivariate logistic regression analyses showed advanced nurses were more aware of EBP, had higher knowledge and skills of EBP, and more often implemented EBP than beginning nurses. Linking Evidence to Action The awareness of, beliefs in, attitudes toward, knowledge of, skills in, and behaviors of EBP among advanced nurses were better than those among beginning nurses. The data indicate that a clinical ladder system can serve as a useful means to enhance EBP implementation. PMID:25588625

  4. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies.

    PubMed

    Kalk, N J; Nutt, D J; Lingford-Hughes, A R

    2011-01-01

    The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been extended to other anxiety disorders, which share with panic disorder characteristic subjective anxiety and physiological symptoms of excess sympathetic activity. For example, Generalized Anxiety Disorder is characterized by chronic free-floating anxiety, muscle tension, palpitation and insomnia. It has been proposed that there is chronic central hypersecretion of noradrenaline in Generalized Anxiety Disorder, with consequent hyporesponsiveness of central post-synaptic receptors. With regards to other disorders, it has been suggested that there is noradrenergic involvement or derangement, but a more specific hypothesis has not been enunciated. This paper reviews the evidence for noradrenergic dysfunction in anxiety disorders, derived from indirect measures of noradrenergic function in clinical populations.

  5. A patient with type I CD36 deficiency whose myocardium accumulated 123I-BMIPP after 4 years.

    PubMed

    Ito, K; Sugihara, H; Tanabe, T; Zen, K; Hikosaka, T; Adachi, Y; Katoh, S; Azuma, A; Nakagawa, M

    2001-06-01

    A 73-year-old man with aortic regurgitation was examined by 123I-alpha-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) in 1995. Myocardial accumulation was not evident on either the early or the delayed image obtained 15 minutes and 3 hours, respectively, after injecting 123I-BMIPP. Flow cytometric analysis of CD36 expression in monocytes and platelets identified a type I CD36 deficiency. The patient was hospitalized for severe heart failure in 1999. Upon admission, the cardiothoracic ratio on chest X-rays was 73%, and the left ventricular end-diastolic diameter on echocardiograms was enlarged to 77 mm. On the second day, we performed 123I-BMIPP myocardial SPECT. Myocardial accumulation was evident in the delayed, but not in the early image. We repeated 123I-BMIPP myocardial SPECT on the 10th day after admission. Myocardial accumulation was evident on both early and delayed images. 99mTc-tetrofosmin myocardial SPECT was immediately performed after 123I-BMIPP myocardial SPECT to distinguish myocardial from pooling images in the left ventricle, but, because the images from both 99Tc-tetrofosmin and 123I-BMIPP myocardial SPECT were idential, we considered that the 123I-BMIPP myocardial SPECT images reflected the actual myocardial condition. The CD36 molecule transports long-chain fatty acid (LCFA) on the myocardial membrane, but 123I-BMIPP scintigraphy does not show any myocardial accumulation in patients with type I CD36 deficiency, indicating that myocardial LCFA uptake occurs through CD36 on the human myocardial membrane. Even though our patient had type I CD36 deficiency, BMIPP was uptaken by the myocardium during heart failure, suggesting a variant pathway on the human myocardial membrane for LCFA uptake.

  6. Compression of the Fourth Ventricle Using a Craniosacral Osteopathic Technique: A Systematic Review of the Clinical Evidence

    PubMed Central

    Żurowska, Anna; Samborski, Włodzimierz; Paprocka-Borowicz, Małgorzata

    2017-01-01

    Compression of the fourth ventricle (CV4) is a well-known osteopathic procedure, utilized by osteopaths, osteopathic physicians, craniosacral therapists, physical therapists, and manual therapists as part of their healthcare practice based on some evidence suggesting impact on nervous system functions. The main objective of the study was to identify randomized controlled trials (RCTs) assessing the clinical benefits of CV4 and to show the evidence supporting clinical prescriptions, guides, and advice in treating. A computerized search of the PubMed, CINAHL Complete, Scopus, Web of Science, and ScienceDirect databases was performed. Two filters were used (article type: RCTs; species: humans). The methodological quality of the trials was assessed using the Downs and Black quality checklist for healthcare intervention studies. Only six studies met the inclusion criteria, of which four were RCTs and two were observational studies. The Downs and Black score ranged from 17 to 24 points out of a maximum of 27 points. The present review revealed the paucity of CV4 research in patients with different clinical problems, as five out of six included studies investigated healthy adults. According to the results of the included studies, CV4 may be beneficial for patients with different functional problems. PMID:29234380

  7. Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

    PubMed Central

    Tomé-Carneiro, Joao; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos

    2013-01-01

    Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol-based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of ‘potential’ benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called ‘Resveratrol Paradox’, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently

  8. Treatment of diverticular disease: an update on latest evidence and clinical implications.

    PubMed

    Carabotti, Marilia; Annibale, Bruno

    2018-01-01

    Diverticular disease (DD) is a common condition, especially in Western countries. In about 80% of patients, colonic diverticula remain asymptomatic (diverticulosis), while approximately 20% of patients may develop abdominal symptoms (symptomatic uncomplicated diverticular disease, SUDD) and, eventually complications as acute diverticulitis (AD). The management of this condition has been improved, and in the last five years European countries and the USA have published guidelines and recommendations. To summarize the latest evidence and clinical implication in treatment of DD focusing the attention either on the treatment of diverticulosis, SUDD and AD together with the primary and secondary prevention of diverticulitis. The present review was based on the latest evidence in the treatment of DD in the last 10 years. In the last 5 years, six countries issued guidelines on DD with differences regarding covered topics and recommendations regarding treatments. At present there is a lack of rationale for drug use in patients with asymptomatic diverticulosis, but there are limited indications to suggest an increase in dietary fibre to reduce risk of DD. To achieve symptomatic relief in SUDD patients, several therapeutic strategies with fibre, probiotics, rifaximin and mesalazine have been proposed even if a standard therapeutic approach remained to be defined. Agreement has been reached for the management of AD, since recent guidelines showed that antibiotics can be used selectively, rather than routinely in uncomplicated AD, although use of antibiotics remained crucial in the management of complicated cases. With regard to treatment for the primary and secondary prevention of AD, the efficacy of rifaximin and mesalazine has been proposed although with discordant recommendations among guidelines. Treatment of DD represented an important challenge in clinical practice, especially concerning management of SUDD and the primary and secondary prevention of AD.

  9. Adapting evidence-based clinical practice guidelines at university teaching hospitals: A model for the Eastern Mediterranean Region.

    PubMed

    Amer, Yasser S; Wahabi, Hayfaa A; Abou Elkheir, Manal M; Bawazeer, Ghada A; Iqbal, Shaikh M; Titi, Maher A; Ekhzaimy, Aishah; Alswat, Khalid A; Alzeidan, Rasmieh A; Al-Ansary, Lubna A

    2018-04-24

    Clinical practice guidelines (CPGs) are significant tools for evidence-based health care quality improvement. The CPG program at King Saud University was launched as a quality improvement program to fulfil the international accreditation standards. This program was a collaboration between the Research Chair for Evidence-Based Healthcare and Knowledge Translation and the Quality Management Department. This study aims to develop a fast-track method for adaptation of evidence-based CPGs and describe results of the program. Twenty-two clinical departments participated in the program. Following a CPGs awareness week directed to all health care professionals (HCPs), 22 teams were trained to set priorities, search, screen, assess, select, and customize the best available CPGs. The teams were technically supported by the program's CPG advisors. To address the local health care context, a modified version of the ADAPTE was used where recommendations were either accepted or rejected but not changed. A strict peer-review process for clinical content and methodology was employed. In addition to raising awareness and building capacity, 35 CPGs were approved for implementation by March 2018. These CPGs were integrated with other existing projects such as accreditation, electronic medical records, performance management, and training and education. Preliminary implementation audits suggest a positive impact on patient outcomes. Leadership commitment was a strength, but the high turnover of the team members required frequent and extensive training for HCPs. This model for CPG adaptation represents a quick, practical, economical method with a sense of ownership by staff. Using this modified version can be replicated in other countries to assess its validity. © 2018 John Wiley & Sons, Ltd.

  10. Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations

    PubMed Central

    Liu, Tian; Wang, Zhixin; Tai, Minghui; Meng, Fandi; Zhang, Jingyao; Wan, Yong; Mao, Ping; Dong, Xiaoqun; Liu, Chang; Niu, Wenquan; Dong, Shunbin

    2016-01-01

    Evidence is accumulating highlighting the importance of extracellular miRNA as a novel biomarker for diagnosing various kinds of malignancies. MiR-21 is one of the most studied miRNAs and is over-expressed in cancer tissues. To explore the clinical implications and secretory mechanisms of extracellular miR-21, we firstly meta-analyzed the diagnostic efficiency of extracellular miR-21 in different cancer types. Eighty-one studies based on 59 articles were finally included. In our study, extracellular miR-21 was observed to exhibit an outstanding diagnostic accuracy in detecting brain cancer (area under the summary receiver operating characteristic curve or AUC = 0.94), and this accuracy was more obvious in glioma diagnosis (AUC = 0.95). Our validation study (n = 45) further confirmed the diagnostic and prognostic role of miR-21 in cerebrospinal fluid (CSF) for glioma. These findings inspired us to explore the biological function of miR-21. We next conducted mechanistic investigations to explain the secretory mechanisms of extracellular miR-21 in glioma. TGF-β/Smad3 signaling was identified to participate in mediating the release of miR-21 from glioma cells. Further targeting TGF-β/Smad3 signaling using galunisertib, an inhibitor of the TGF-β type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. Taken together, CSF-based miR-21 might serve as a potential biomarker for diagnosing brain cancer, especially for patients with glioma. Moreover, extracellular levels of miR-21 were affected by exogenous TGF-β activity and galunisertib treatment. PMID:27166186

  11. Changing Nephrology Nurses' Beliefs about the Value of Evidence-Based Practice and Their Ability to Implement in Clinical Practice.

    PubMed

    Hain, Debra; Haras, Mary S

    2015-01-01

    A rapidly evolving healthcare environment demands sound research evidence to inform clinical practice and improve patient outcomes. Over the past several decades, nurses have generated new knowledge by conducting research studies, but it takes time for this evidence to be implemented in practice. As nurses strive to be leaders and active participants in healthcare redesign, it is essential that they possess the requisite knowledge and skills to engage in evidence-based practice (EBP). Professional nursing organizations can make substantial contributions to the move healthcare quality forward by providing EBP workshops similar to those conducted by the American Nephrology Nurses'Association.

  12. Direct Observation of Clinical Skills Feedback Scale: Development and Validity Evidence.

    PubMed

    Halman, Samantha; Dudek, Nancy; Wood, Timothy; Pugh, Debra; Touchie, Claire; McAleer, Sean; Humphrey-Murto, Susan

    2016-01-01

    Construct: This article describes the development and validity evidence behind a new rating scale to assess feedback quality in the clinical workplace. Competency-based medical education has mandated a shift to learner-centeredness, authentic observation, and frequent formative assessments with a focus on the delivery of effective feedback. Because feedback has been shown to be of variable quality and effectiveness, an assessment of feedback quality in the workplace is important to ensure we are providing trainees with optimal learning opportunities. The purposes of this project were to develop a rating scale for the quality of verbal feedback in the workplace (the Direct Observation of Clinical Skills Feedback Scale [DOCS-FBS]) and to gather validity evidence for its use. Two panels of experts (local and national) took part in a nominal group technique to identify features of high-quality feedback. Through multiple iterations and review, 9 features were developed into the DOCS-FBS. Four rater types (residents n = 21, medical students n = 8, faculty n = 12, and educators n = 12) used the DOCS-FBS to rate videotaped feedback encounters of variable quality. The psychometric properties of the scale were determined using a generalizability analysis. Participants also completed a survey to gather data on a 5-point Likert scale to inform the ease of use, clarity, knowledge acquisition, and acceptability of the scale. Mean video ratings ranged from 1.38 to 2.96 out of 3 and followed the intended pattern suggesting that the tool allowed raters to distinguish between examples of higher and lower quality feedback. There were no significant differences between rater type (range = 2.36-2.49), suggesting that all groups of raters used the tool in the same way. The generalizability coefficients for the scale ranged from 0.97 to 0.99. Item-total correlations were all above 0.80, suggesting some redundancy in items. Participants found the scale easy to use (M = 4.31/5) and clear

  13. Death rates reflect accumulating brain damage in arthropods.

    PubMed

    Fonseca, Duane B; Brancato, Carolina L; Prior, Andrew E; Shelton, Peter M J; Sheehy, Matt R J

    2005-09-22

    We present the results of the first quantitative, whole-lifespan study of the relationship between age-specific neurolipofuscin concentration and natural mortality rate in any organism. In a convenient laboratory animal, the African migratory locust, Locusta migratoria, we find an unusual delayed-onset neurolipofuscin accumulation pattern that is highly correlated with exponentially accelerating age-specific Gompertz-Makeham death rates in both males (r=0.93, p=0.0064) and females (r=0.97, p=0.0052). We then test the conservation of this association by aggregating the locust results with available population-specific data for a range of other terrestrial, freshwater, marine, tropical and temperate arthropods whose longevities span three orders of magnitude. This synthesis shows that the strong association between neurolipofuscin deposition and natural mortality is a phylogenetically and environmentally widespread phenomenon (r=0.96, p < 0.0001). These results highlight neurolipofuscin as a unique and outstanding integral biomarker of ageing. They also offer compelling evidence for the proposal that, in vital organs like the brain, either the accumulation of toxic garbage in the form of lipofuscin itself, or the particular molecular reactions underlying lipofuscinogenesis, including free-radical damage, are the primary events in senescence.

  14. Methodological approaches to developing and establishing the body of evidence on post-marketing Chinese medicine safety.

    PubMed

    Liao, Xing; Robinson, Nicola

    2013-07-01

    Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, postmarketing surveillance (PMS) has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions (ADRs). Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detect ADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.

  15. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.

    PubMed

    Sarris, Jerome; McIntyre, Erica; Camfield, David A

    2013-04-01

    Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations of anxiolytic activity. A search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) for English language papers using the search terms 'anxiety' OR 'anxiety disorder' OR 'generalized anxiety disorder' OR 'social phobia' OR 'post-traumatic stress disorder' OR 'panic disorder' OR 'agoraphobia' OR 'obsessive compulsive disorder' in combination with the search terms 'Herb*' OR 'Medicinal Plants' OR 'Botanical Medicine' OR 'Chinese herb*', in addition to individual herbal medicines. This search of the literature revealed 1,525 papers, of which 53 plants were included in the review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed here in part two), with the other 32 having solely preclinical evidence (reviewed in part one). Support for efficacy was found for chronic use (i.e. greater than one day) of the following herbs in treating a range of anxiety disorders in human clinical trials: Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis and Echium

  16. Do firms underinvest in long-term research? Evidence from cancer clinical trials

    PubMed Central

    Budish, Eric; Roin, Benjamin N.

    2015-01-01

    We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials – and hence, project durations – are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design. PMID:26345455

  17. Silence and voicing accumulations in Italian primary school teachers with and without voice disorders

    PubMed Central

    Bottalico, Pasquale; Graetzer, Simone; Astolfi, Arianna; Hunter, Eric J.

    2016-01-01

    Objectives The relationship between the silence and voicing accumulations of primary school teachers and the teachers’ clinical status was examined. The goal was to determine whether more voicing accumulations and fewer silence accumulations were measured for the vocally unhealthy subjects than for the healthy subjects, which would imply more vocal loading and fewer short-term recovery moments. Methods 26 Italian primary school teachers were allocated by clinicians to three groups: (1) with organic voice disorders, (2) with subjectively mild organic alteration and/or functional voice symptoms, and (3) normal voice quality and physiology. Continuous silence and voicing periods were measured with the APM3200 during the teachers’ 4-hour workdays. The accumulations were grouped into 7 time intervals, ranging from 0.03–0.9 s to 3.16–10 s, according to Italian prosody. The effects of group on silence and voicing accumulations were evaluated. Results Regarding silence accumulations, Group 1 accumulated higher values in intervals between 0.1 and 3.15 s than other groups, while Groups 2 and 3 did not differ from each other. Voicing accumulations between 0.17 and 3.15 s were higher for subjects with a structural disorder. A higher time dose was accumulated by these subjects (40.6%) than other subjects (Group 2, 31.9%; Group 3, 32.3%). Conclusions While previous research has suggested that a rest period of a few seconds may produce some vocal fatigue recovery, these results indicate that periods shorter than 3.16 s may not have an observable effect on recovery. The results provide insight into how vocal fatigue and vocal recovery may relate to voice disorders in occupational voice users. PMID:27316793

  18. Handling of peripheral intravenous cannulae: effects of evidence-based clinical guidelines.

    PubMed

    Ahlqvist, Margary; Bogren, Agneta; Hagman, Sari; Nazar, Isabel; Nilsson, Katarina; Nordin, Karin; Valfridsson, Berit Sunde; Söderlund, Mona; Nordström, Gun

    2006-11-01

    This study aimed at evaluating the outcome of implemented evidence-based clinical guidelines by means of surveying the frequency of thrombophlebitis, nurses' care, handling and documentation of peripheral intravenous cannulae. Peripheral intravenous cannulae are frequently used for vascular access and, thereby, the patients will be exposed to local and systemic infectious complications. Evidence-based knowledge of how to prevent these complications and how to care for patients with peripheral intravenous cannula is therefore of great importance. Deficient care, handling and documentation of peripheral intravenous cannulae have previously been reported. A cross-sectional survey was conducted by a group of nurses at three wards at a university hospital before and after the implementation of the evidence-based guidelines. A structured observation protocol was used to review the frequency of thrombophlebitis, the nurses' care, handling and the documentation of peripheral intravenous cannulae in the patient's record. A total of 107 and 99 cannulae respectively were observed before and after the implementation of the guidelines. The frequency of peripheral intravenous cannulae without signs of thrombophlebitis increased by 21% (P < 0.01) and the use of cannula size 0.8 mm increased by 22% (P < 0.001). Nurses' documentation of peripheral intravenous cannula improved significantly (P < 0.001). We conclude that implementation of the guidelines resulted in significant improvements by means of decreased frequency of signs of thrombophlebitis, increased application of smaller cannula size (0.8 mm), as well as of the nurses' documentation in the patient's record. Further efforts to ameliorate care and handling of peripheral intravenous cannulae are needed. This can be done by means of increasing nurses' knowledge and recurrent quality reviews. Well-informed patients can also be more involved in the care than is common today.

  19. The virtues of evidence.

    PubMed

    Zarkovich, Erica; Upshur, R E G

    2002-01-01

    Evidence-based medicine has been defined as the conscientious and judicious use of current best evidence in making clinical decisions. This paper will attempt to explicate the terms "conscientious" and "judicious" within the evidence-based medicine definition. It will be argued that "conscientious" and "judicious" represent virtue terms derived from virtue ethics and virtue epistemology. The identification of explicit virtue components in the definition and therefore conception of evidence-based medicine presents an important starting point in the connection between virtue theories and medicine itself. In addition, a unification of virtue theories and evidence-based medicine will illustrate the need for future research in order to combine the fields of virtue-based approaches and clinical practice.

  20. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions

    PubMed Central

    Bingham, Clifton O.; Moni, Malini

    2015-01-01

    Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions. PMID:23455329