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Sample records for accumulating clinical evidence

  1. 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

  2. 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

  3. 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.

  4. Distinct relationships of parietal and prefrontal cortices to evidence accumulation

    PubMed Central

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

    2014-01-01

    Gradual accumulation of evidence is thought to be fundamental for decision-making, and its neural correlates have been found in multiple brain regions1–8. Here we develop a generalizable method to measure tuning curves that specify the relationship between neural responses and mentally-accumulated evidence, and apply it to distinguish the encoding of decision variables in posterior parietal cortex (PPC) and prefrontal cortex (frontal orienting fields, FOF). We recorded the firing rates of neurons in PPC and FOF from rats performing a perceptual decision-making task. Classical analyses uncovered correlates of accumulating evidence, similar to previous observations in primates and also similar across the two regions. However, tuning curve assays revealed that while the PPC encodes a graded value of the accumulating evidence, the FOF has a more categorical encoding that indicates, throughout the trial, the decision provisionally favored by the evidence accumulated so far. Contrary to current views3,5,7–9, this suggests that premotor activity in frontal cortex does not play a role in the accumulation process, but instead has a more categorical function, such as transforming accumulated evidence into a discrete choice. To causally probe the role of FOF activity, we optogenetically silenced it during different timepoints of the trial. Consistent with a role in committing to a categorical choice at the end of the evidence accumulation process, but not consistent with a role during the accumulation itself, a behavioral effect was observed only when FOF silencing occurred at the end of the perceptual stimulus. Our results place important constraints on the circuit logic of brain regions involved in decision-making. PMID:25600270

  5. Neural evidence accumulation persists after choice to inform metacognitive judgments

    PubMed Central

    Murphy, Peter R; Robertson, Ian H; Harty, Siobhán; O'Connell, Redmond G

    2015-01-01

    The ability to revise one’s certainty or confidence in a preceding choice is a critical feature of adaptive decision-making but the neural mechanisms underpinning this metacognitive process have yet to be characterized. In the present study, we demonstrate that the same build-to-threshold decision variable signal that triggers an initial choice continues to evolve after commitment, and determines the timing and accuracy of self-initiated error detection reports by selectively representing accumulated evidence that the preceding choice was incorrect. We also show that a peri-choice signal generated in medial frontal cortex provides a source of input to this post-decision accumulation process, indicating that metacognitive judgments are not solely based on the accumulation of feedforward sensory evidence. These findings impart novel insights into the generative mechanisms of metacognition. DOI: http://dx.doi.org/10.7554/eLife.11946.001 PMID:26687008

  6. 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.

  7. Clinical issues of mucus accumulation in COPD

    PubMed Central

    Ramos, Frederick L; Krahnke, Jason S; Kim, Victor

    2014-01-01

    Airway mucus is part of the lung’s native immune function that traps particulates and microorganisms, enabling their clearance from the lung by ciliary transport and cough. Mucus hypersecretion and chronic productive cough are the features of the chronic bronchitis and chronic obstructive pulmonary disease (COPD). Overproduction and hypersecretion by goblet cells and the decreased elimination of mucus are the primary mechanisms responsible for excessive mucus in chronic bronchitis. Mucus accumulation in COPD patients affects several important outcomes such as lung function, health-related quality of life, COPD exacerbations, hospitalizations, and mortality. Nonpharmacologic options for the treatment of mucus accumulation in COPD are smoking cessation and physical measures used to promote mucus clearance. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. PMID:24493923

  8. Auditory Streaming as an Online Classification Process with Evidence Accumulation

    PubMed Central

    Barniv, Dana; Nelken, Israel

    2015-01-01

    When human subjects hear a sequence of two alternating pure tones, they often perceive it in one of two ways: as one integrated sequence (a single "stream" consisting of the two tones), or as two segregated sequences, one sequence of low tones perceived separately from another sequence of high tones (two "streams"). Perception of this stimulus is thus bistable. Moreover, subjects report on-going switching between the two percepts: unless the frequency separation is large, initial perception tends to be of integration, followed by toggling between integration and segregation phases. The process of stream formation is loosely named “auditory streaming”. Auditory streaming is believed to be a manifestation of human ability to analyze an auditory scene, i.e. to attribute portions of the incoming sound sequence to distinct sound generating entities. Previous studies suggested that the durations of the successive integration and segregation phases are statistically independent. This independence plays an important role in current models of bistability. Contrary to this, we show here, by analyzing a large set of data, that subsequent phase durations are positively correlated. To account together for bistability and positive correlation between subsequent durations, we suggest that streaming is a consequence of an evidence accumulation process. Evidence for segregation is accumulated during the integration phase and vice versa; a switch to the opposite percept occurs stochastically based on this evidence. During a long phase, a large amount of evidence for the opposite percept is accumulated, resulting in a long subsequent phase. In contrast, a short phase is followed by another short phase. We implement these concepts using a probabilistic model that shows both bistability and correlations similar to those observed experimentally. PMID:26671774

  9. 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

  10. Evidence accumulation in the integrated and primed Stroop tasks.

    PubMed

    Kinoshita, Sachiko; de Wit, Bianca; Aji, Melissa; Norris, Dennis

    2017-03-31

    We report distributional analyses of response times (RT) in two variants of the color-word Stroop task using manual keypress responses. In the classic Stroop task, in which the color and word dimensions are integrated into a single stimulus, the Stroop congruence effect increased across the quantiles. In contrast, in the primed Stroop task, in which the distractor word is presented ahead of colored symbols, the Stroop congruence effect was manifested solely as a distributional shift, remaining constant across the quantiles. The distributional-shift pattern mirrors the semantic-priming effect that has been reported in semantic categorization tasks. The results are interpreted within the framework of evidence accumulation, and implications for the roles of task conflict and informational conflict are discussed.

  11. Categorisation through evidence accumulation in an active vision system

    NASA Astrophysics Data System (ADS)

    Mirolli, Marco; Ferrauto, Tomassino; Nolfi, Stefano

    2010-12-01

    In this paper, we present an artificial vision system that is trained with a genetic algorithm for categorising five different kinds of images (letters) of different sizes. The system, which has a limited field of view, can move its eye so as to explore the images visually. The analysis of the system at the end of the training process indicates that correct categorisation is achieved by (1) exploiting sensory-motor coordination so as to experience stimuli that facilitate discrimination, and (2) integrating perceptual and/or motor information over time through a process of accumulation of partially conflicting evidence. We discuss our results with respect to the possible different strategies for categorisation and to the possible roles that action can play in perception.

  12. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  13. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    PubMed Central

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  14. 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.

  15. Dispersed and accumulated organic matter in fractures: Primary migration evidences

    SciTech Connect

    Lopez, L.; Pasquali, J. )

    1993-02-01

    Concentrated organic matter accumulated in fractures (organic rich fraction) and dispersed organic matter (total rock) of the source rocks of the Querecual and San Antonio formations of the Eastern Venezuelan basin were studied. The distribution of organic matter was studied in polished sections. Sample were analyzed for total organic carbon (Ct), total bitumen and the n-alkane fraction within the bitumen. Dispersed and concentrated organic matter were analyzed separately, and the pertinent differences were established. Concentrated organic matter, probably accumulated to due migration of dispersed organic matter into fractures, or low pressure zones is deficient in n-alkanes of low molecular weight. This fact is interpreted as the result of the migration process that allows the preferential movement of light components of low polarity. It seems that the products of kerogen maturation start their transformation to materials more like crude oils from their primary migration, stage that is to say, within the source rock.

  16. Pharmacogenetic testing: current evidence of clinical utility

    PubMed Central

    Haga, Susanne B.

    2013-01-01

    Over the last decade, the number of clinical pharmacogenetic tests has steadily increased as understanding of the role of genes in drug response has grown. However, uptake of these tests has been slow, due in large part to the lack of robust evidence demonstrating clinical utility. We review the evidence behind four pharmacogenetic tests and discuss the barriers and facilitators to uptake: (1) warfarin (drug safety and efficacy); (2) clopidogrel (drug efficacy); (3) codeine (drug safety and efficacy); and (4) abacavir (drug safety). Future efforts should be directed toward addressing these issues and considering additional approaches to generating evidence basis to support clinical use of pharmacogenetic tests. PMID:24020014

  17. Evidence Accumulator or Decision Threshold - Which Cortical Mechanism are We Observing?

    PubMed

    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.

  18. How Many Dystonias? Clinical Evidence

    PubMed Central

    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. PMID:28217105

  19. 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

  20. [Osteoarticular scintigraphy in comparison with clinical evidence].

    PubMed

    del Puente, Antonio; Venditti, Carlo; Peluso, Rosario; Esposito, Antonella; Cimmino, Michele; De Luca Bossa, Rosa; Loi, Gabriella; Spanò, Angelo; Oriente, Alfonso; Oriente, Pasquale

    2003-01-01

    Bone scintigraphy is a technique which is often resorted to in diagnostic rheumatology. There are few data on the effective relevance of bone scintigraphy in the evaluation of chronic inflammatory diseases of the joints. The aim of this study was to compare the results of bone scintigraphy with clinical evidence in patients with rheumatoid arthritis or osteoarthritis. Seventy-five patients were submitted to total body bone scintigraphy (44 rheumatoid arthritis, 31 osteoarthritis). The nuclear medicine specialist indicated the list of joints showing uptake. For the same patients a rheumatologist indicated the number of affected joints. The laboratory and clinical data were recorded. The patients were first stratified according to the prevalence of the clinical evidence and scintigraphic uptake. The distribution was found to be not significant. Only 5.3% of patients showed no uptake. Thirty-three patients had no clinical evidence of disease; among these, 30 showed joint uptake. Considering only the patients with clinical evidence, 97.6% showed joint uptake. These results were confirmed even when the data were analyzed by sex, disease and therapy. Considering the patients with clinical evidence, the uptake/clinical ratio did not show any significant correlation. The number of joints with clinical evidence correlated with the erythrocyte sedimentation rate. The number of joints showing uptake correlated only with age. In conclusion, on average, scintigraphy, performed in patients with rheumatoid arthritis and osteoarthritis, highlights a significantly higher number of joints involved as compared to what would be expected on the basis of clinical evaluation. It remains to be defined whether this is an overestimation related to the characteristics of the scan or whether it is sign of a higher sensitivity in highlighting the site of inflammation. Against the latter hypothesis is the absence of correlation with the inflammatory indexes.

  1. Accumulator

    NASA Technical Reports Server (NTRS)

    Fenwick, J. R.; Karigan, G. H. (Inventor)

    1977-01-01

    An accumulator particularly adapted for use in controlling the pressure of a stream of fluid in its liquid phase utilizing the fluid in its gaseous phase was designed. The accumulator is characterized by a shell defining a pressure chamber having an entry throat for a liquid and adapted to be connected in contiguous relation with a selected conduit having a stream of fluid flowing through the conduit in its liquid phase. A pressure and volume stabilization tube, including an array of pressure relief perforations is projected into the chamber with the perforations disposed adjacent to the entry throat for accommodating a discharge of the fluid in either gaseous or liquid phases, while a gas inlet and liquid to gas conversion system is provided, the chamber is connected with a source of the fluid for continuously pressuring the chamber for controlling the pressure of the stream of liquid.

  2. Interference effects of choice on confidence: Quantum characteristics of evidence accumulation.

    PubMed

    Kvam, Peter D; Pleskac, Timothy J; Yu, Shuli; Busemeyer, Jerome R

    2015-08-25

    Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system.

  3. Interference effects of choice on confidence: Quantum characteristics of evidence accumulation

    PubMed Central

    Kvam, Peter D.; Pleskac, Timothy J.

    2015-01-01

    Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system. PMID:26261322

  4. Representation of accumulating evidence for a decision in two parietal areas.

    PubMed

    de Lafuente, Victor; Jazayeri, Mehrdad; Shadlen, Michael N

    2015-03-11

    Decisions are often made by accumulating evidence for and against the alternatives. The momentary evidence represented by sensory neurons is accumulated by downstream structures to form a decision variable, linking the evolving decision to the formation of a motor plan. When decisions are communicated by eye movements, neurons in the lateral intraparietal area (LIP) represent the accumulation of evidence bearing on the potential targets for saccades. We now show that reach-related neurons from the medial intraparietal area (MIP) exhibit a gradual modulation of their firing rates consistent with the representation of an evolving decision variable. When decisions were communicated by saccades instead of reaches, decision-related activity was attenuated in MIP, whereas LIP neurons were active while monkeys communicated decisions by saccades or reaches. Thus, for decisions communicated by a hand movement, a parallel flow of sensory information is directed to parietal areas MIP and LIP during decision formation.

  5. Representation of Accumulating Evidence for a Decision in Two Parietal Areas

    PubMed Central

    de Lafuente, Victor; Jazayeri, Mehrdad

    2015-01-01

    Decisions are often made by accumulating evidence for and against the alternatives. The momentary evidence represented by sensory neurons is accumulated by downstream structures to form a decision variable, linking the evolving decision to the formation of a motor plan. When decisions are communicated by eye movements, neurons in the lateral intraparietal area (LIP) represent the accumulation of evidence bearing on the potential targets for saccades. We now show that reach-related neurons from the medial intraparietal area (MIP) exhibit a gradual modulation of their firing rates consistent with the representation of an evolving decision variable. When decisions were communicated by saccades instead of reaches, decision-related activity was attenuated in MIP, whereas LIP neurons were active while monkeys communicated decisions by saccades or reaches. Thus, for decisions communicated by a hand movement, a parallel flow of sensory information is directed to parietal areas MIP and LIP during decision formation. PMID:25762677

  6. Neural oscillations and synchronization differentially support evidence accumulation in perceptual and value-based decision making.

    PubMed

    Polanía, Rafael; Krajbich, Ian; Grueschow, Marcus; Ruff, Christian C

    2014-05-07

    Organisms make two types of decisions on a regular basis. Perceptual decisions are determined by objective states of the world (e.g., melons are bigger than apples), whereas value-based decisions are determined by subjective preferences (e.g., I prefer apples to melons). Theoretical accounts suggest that both types of choice involve neural computations accumulating evidence for the choice alternatives; however, little is known about the overlap or differences in the processes underlying perceptual versus value-based decisions. We analyzed EEG recordings during a paradigm where perceptual- and value-based choices were based on identical stimuli. For both types of choice, evidence accumulation was evident in parietal gamma-frequency oscillations, whereas a similar frontal signal was unique for value-based decisions. Fronto-parietal synchronization of these signals predicted value-based choice accuracy. These findings uncover how decisions emerge from topographic- and frequency-specific oscillations that accumulate distinct aspects of evidence, with large-scale synchronization as a mechanism integrating these spatially distributed signals.

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

    PubMed Central

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

    2016-01-01

    Background: 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. Methods: 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. Conclusion: 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

  8. Ultrastructural evidence for iron accumulation within the tube of Vestimentiferan Ridgeia piscesae.

    PubMed

    Peng, Xiaotong; Zhou, Huaiyang; Yao, Huiqiang; Li, Jiangtao; Wu, Zijun

    2009-10-01

    This study reports on the accumulation of iron within the tube wall of the deep sea vent macro invertebrate Vestimentiferan Ridgeia piscesae collected from Juan de Fuca ridge. Combining an array of approaches including environmental scanning electron microscope (ESEM), electron probe micro-analysis (EPMA), X-ray microanalysis (EDS) and transmission electron microscope (TEM), we provide evidences for the influence of prokaryotic organisms on the accumulation of metals on and within the tube wall. Two types of iron-rich minerals such as iron oxides and framboidal pyrites are identified within or on the tube wall. Our results reveal the presence of prokaryotic organism is apparently responsible for the early accumulation of iron-rich minerals in the tube wall. The implications of the biomineralisation of iron in tube wall at hydrothermal vents are discussed.

  9. 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

  10. Current clinical evidence on pioglitazone pharmacogenomics

    PubMed Central

    Kawaguchi-Suzuki, Marina; Frye, Reginald F.

    2013-01-01

    Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Pioglitazone is approved for use in the management of type 2 diabetes mellitus (T2DM), but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p = 0.018). Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone is being

  11. 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.

  12. Sources of noise during accumulation of evidence in unrestrained and voluntarily head-restrained rats

    PubMed Central

    Scott, Benjamin B; Constantinople, Christine M; Erlich, Jeffrey C; Tank, David W; Brody, Carlos D

    2015-01-01

    Decision-making behavior is often characterized by substantial variability, but its source remains unclear. We developed a visual accumulation of evidence task designed to quantify sources of noise and to be performed during voluntary head restraint, enabling cellular resolution imaging in future studies. Rats accumulated discrete numbers of flashes presented to the left and right visual hemifields and indicated the side that had the greater number of flashes. Using a signal-detection theory-based model, we found that the standard deviation in their internal estimate of flash number scaled linearly with the number of flashes. This indicates a major source of noise that, surprisingly, is not consistent with the widely used 'drift-diffusion modeling' (DDM) approach but is instead closely related to proposed models of numerical cognition and counting. We speculate that this form of noise could be important in accumulation of evidence tasks generally. DOI: http://dx.doi.org/10.7554/eLife.11308.001 PMID:26673896

  13. Evidence Accumulation in Obsessive-Compulsive Disorder: the Role of Uncertainty and Monetary Reward on Perceptual Decision-Making Thresholds

    PubMed Central

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

    2015-01-01

    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. PMID:25425323

  14. Isotopic evidence for in-lake production of accumulating nitrate in Lake Superior.

    PubMed

    Finlay, Jacques C; Sterner, Robert W; Kumar, Sanjeev

    2007-12-01

    A century-long increase in nitrate (NO3-) in the water column of Lake Superior is a classic example of recent nitrogen accumulation in ecosystems, but its cause and relationship to historical NO3- deposition is unknown. We used stable isotope ratios of oxygen and nitrogen in nitrate (delta18O-NO3 and delta15N-NO3) to examine its sources in this large lake, which represents 10% of the world's surficial liquid freshwater. The most parsimonious hypothesis to explain the rise in NO3- is that the lake is accruing NO3- deposited directly on the lake surface because it is too unproductive to completely assimilate all of it. Data for delta18O-NO3 in external sources and the water column, however, are inconsistent with this hypothesis. Instead, the isotopic evidence indicates strongly that the accumulating NO3- is almost entirely derived from nitrification occurring within the lake. While increases in atmospheric deposition of NO3- may have played a role in its buildup in the lake, other factors such as increases in NH4+ and dissolved organic nitrogen inputs from precipitation or rivers, increases in nitrogen fluxes from the sediments, and decreases in burial rates must also be considered as potential drivers of rising NO3-. The sustained accumulation of nitrogen in Lake Superior is thus more complex and incompletely understood than previously assumed.

  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. 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

    2017-02-27

    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 allow for a 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 (EEG), this paradigm enables isolation of discrete neural signals reflecting the key neural processes needed for making these detection decisions; including 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 alpha power measured prior to 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 StatementThe 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 the existence of

  17. 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.

  18. Clinical evidence for Japanese population based on prospective studies--linking clinical trials and clinical practice.

    PubMed

    Ogawa, Hisao; Kojima, Sunao

    2009-10-01

    "Evidence-based medicine (EBM)" implies effective and high quality practice for patients based on well-grounded medical science. The success of clinical trials in Japan is essential to build original evidence specific for Japanese patients. Based on this concept, we have performed several large-scale clinical trials to provide EBM, including the Japanese Antiplatelets Myocardial Infarction Study [JAMIS; clinical improvement in acute myocardial infarction (AMI) patients with antiplatelet therapy], the Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI; comparison of the effects of beta-blockers and calcium antagonists on cardiovascular events in post-AMI patients), a multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors in patients with AMI (MUSASHI; effects of statin therapy on cardiovascular events in patients with AMI), and the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD trial; efficacy of low-dose aspirin therapy for primary prevention of atherosclerotic events in type 2 diabetic patients). The results of these prospective studies were directly linked with clinical practice. We have acquired the know-how of large-scale clinical trials; an important point is to have passion for "buildup evidence specific for the Japanese" and to recruit subjects for enrollment after explaining the significance of "clinical trials for the Japanese".

  19. 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

  20. 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.

  1. Evidence for the future – Designing a clinical trial

    PubMed Central

    Hajebrahimi, Sakineh; Mostafaie, Ali; Sadeghi-Bazargani, Homayoun

    2011-01-01

    The quality of the evidence is a keystone in the understanding of Evidence Based Medicine. Randomized controlled trials (RCTs) rank first among the research designs providing clinical evidence. Knowing about the design of clinical trials is not only the cornerstone of clinical research, but also is a requirement for any clinician who wants to learn about new findings of clinical research in his/her field. Many clinicians have good understanding as well as some misunderstandings about the design of clinical trials. This article is going to provide some crucial comments to be considered in conducting RCTs in order to help in production of better evidence for future of urology research through RCTs PMID:22279317

  2. Searching for Clinical Evidence in CiteSpace

    PubMed Central

    Chen, Chaomei; Chen, Yunan

    2005-01-01

    A crucial step in the practice of evidence-based medicine is to locate the best available evidence regarding to clinical questions. In this article, we demonstrate that combining visualization techniques with traditional methods developed in evidence-based medicine could simplify the task. We describe a unifying framework for searching clinical evidence across multiple sources such as highly cited articles in the Web of Science and articles of particular types of study design in PubMed. We describe the implementation of a prototyping system to visualize the distribution of available evidence in a broader context of the underlying subject domain. We include examples of evidence found in the heart diseases and lung cancer literature. Practical implications on the design of visualization-based evidence searching tools are discussed. PMID:16779014

  3. Silica uptake by Spartina-evidence of multiple modes of accumulation from salt marshes around the world.

    PubMed

    Carey, Joanna C; Fulweiler, Robinson W

    2014-01-01

    Silicon (Si) plays a critical role in plant functional ecology, protecting plants from multiple environmental stressors. While all terrestrial plants contain some Si, wetland grasses are frequently found to have the highest concentrations, although the mechanisms driving Si accumulation in wetland grasses remain in large part uncertain. For example, active Si accumulation is often assumed to be responsible for elevated Si concentrations found in wetland grasses. However, life stage and differences in Si availability in the surrounding environment also appear to be important variables controlling the Si concentrations of wetland grasses. Here we used original data from five North American salt marshes, as well as all known published literature values, to examine the primary drivers of Si accumulation in Spartina, a genus of prolific salt marsh grasses found worldwide. We found evidence of multiple modes of Si accumulation in Spartina, with passive accumulation observed in non-degraded marshes where Spartina was native, while rejective accumulation was found in regions where Spartina was invasive. Evidence of active accumulation was found in only one marsh where Spartina was native, but was also subjected to nutrient over-enrichment. We developed a conceptual model which hypothesizes that the mode of Si uptake by Spartina is dependent on local environmental factors and genetic origin, supporting the idea that plant species should be placed along a spectrum of Si accumulation. We hypothesize that Spartina exhibits previously unrecognized phenotypic plasticity with regard to Si accumulation, allowing these plants to respond to changes in marsh condition. These results provide new insight regarding how salt marsh ecosystems regulate Si exchange at the land-sea interface.

  4. Silica uptake by Spartina—evidence of multiple modes of accumulation from salt marshes around the world

    PubMed Central

    Carey, Joanna C.; Fulweiler, Robinson W.

    2014-01-01

    Silicon (Si) plays a critical role in plant functional ecology, protecting plants from multiple environmental stressors. While all terrestrial plants contain some Si, wetland grasses are frequently found to have the highest concentrations, although the mechanisms driving Si accumulation in wetland grasses remain in large part uncertain. For example, active Si accumulation is often assumed to be responsible for elevated Si concentrations found in wetland grasses. However, life stage and differences in Si availability in the surrounding environment also appear to be important variables controlling the Si concentrations of wetland grasses. Here we used original data from five North American salt marshes, as well as all known published literature values, to examine the primary drivers of Si accumulation in Spartina, a genus of prolific salt marsh grasses found worldwide. We found evidence of multiple modes of Si accumulation in Spartina, with passive accumulation observed in non-degraded marshes where Spartina was native, while rejective accumulation was found in regions where Spartina was invasive. Evidence of active accumulation was found in only one marsh where Spartina was native, but was also subjected to nutrient over-enrichment. We developed a conceptual model which hypothesizes that the mode of Si uptake by Spartina is dependent on local environmental factors and genetic origin, supporting the idea that plant species should be placed along a spectrum of Si accumulation. We hypothesize that Spartina exhibits previously unrecognized phenotypic plasticity with regard to Si accumulation, allowing these plants to respond to changes in marsh condition. These results provide new insight regarding how salt marsh ecosystems regulate Si exchange at the land-sea interface. PMID:24904599

  5. Current penile-rehabilitation strategies: Clinical evidence

    PubMed Central

    Segal, Robert L.; Bivalacqua, Trinity J.; Burnett, Arthur L.

    2013-01-01

    We review the current strategies used for penile rehabilitation (PR) after a radical prostatectomy, where PR is defined as the attempt to restore spontaneous erectile function so that the patient can generate erections with no need for erectile aids. We searched PubMed for relevant reports, using the keywords ‘radical prostatectomy’, ‘penile rehabilitation’, ‘phosphodiesterase inhibitors’, ‘vacuum erection device’, ‘injection therapy’, ‘urethral suppository’, and ‘erectile dysfunction’. In all, 155 articles were identified and reviewed, and had a level of evidence ranging from 1b-4. The use of PR strategies should be based on the patient’s goals after a thorough explanation of realistic expectations, and the risks and consequences of the various treatment options. While a multitude of studies suggest a benefit with PR strategies, there are no established, proven regimens. Further research is needed to establish the optimal approaches to PR. PMID:26558087

  6. Current penile-rehabilitation strategies: Clinical evidence.

    PubMed

    Segal, Robert L; Bivalacqua, Trinity J; Burnett, Arthur L

    2013-09-01

    We review the current strategies used for penile rehabilitation (PR) after a radical prostatectomy, where PR is defined as the attempt to restore spontaneous erectile function so that the patient can generate erections with no need for erectile aids. We searched PubMed for relevant reports, using the keywords 'radical prostatectomy', 'penile rehabilitation', 'phosphodiesterase inhibitors', 'vacuum erection device', 'injection therapy', 'urethral suppository', and 'erectile dysfunction'. In all, 155 articles were identified and reviewed, and had a level of evidence ranging from 1b-4. The use of PR strategies should be based on the patient's goals after a thorough explanation of realistic expectations, and the risks and consequences of the various treatment options. While a multitude of studies suggest a benefit with PR strategies, there are no established, proven regimens. Further research is needed to establish the optimal approaches to PR.

  7. 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…

  8. Clinical evidence of particle beam therapy (proton).

    PubMed

    Ogino, Takashi

    2012-04-01

    Proton beam therapy (PBT) makes it possible to deliver a high concentration of radiation to a tumor using its Bragg peak, and it is simple to utilize as its radiobiological characteristics are identical to those of photon beams. PBT has now been used for half a century, and more than 60,000 patients worldwide are reported to have been treated with proton beams. The most significant change to PBT occurred in the 1990s, when the Loma Linda University Medical Center became the first hospital in the world to operate a medically dedicated proton therapy facility. Following its success, similar medically dedicated facilities have been constructed. Internationally, results have demonstrated the therapeutic superiority of PBT over alternative treatment options for several disease sites. Further advances in PBT are expected from both clinical and technological perspectives.

  9. [Effect of data management quality on clinical research evidence evaluation].

    PubMed

    Gao, Hong-yang; Li, Qing-na; Zhao, Yang; Li, Bo; Rui, Gao

    2015-02-01

    Current clinical evaluation of literature quality has various ways. Most of them lay special emphasis on the evaluation of the design quality, but the evaluation of the implementation process quality is not perfect. Especially data management is not fully emphasized during the enforcement of clinical trials. Data from clinical research were bases for evaluating clinical findings. Although strict specifications and requirements for data management might be strictly written clearly in research protocols, they were not embodied in current clinical research evidence evaluation system. Data management is an important part of implementing the whole clinical trial process, which is a comprehensive reflection of data collecting, logging, sorting, and managing. Its objective is to obtain high quality research data for statistical analysis, thereby coming to a true and reliable conclusion. In order to overall evaluating clinical design and implement, we suggest that present quality evaluation indicators of clinical trails should be completed, and add data management quality evaluation during the whole implement process. Data management plans, standards and requirements for data checking, and management regulations for disobeying data and exception data should be added in quality evaluation indicators for clinical research evidence. The effect of data management quality on clinical research evidence evaluation should be emphasized.

  10. Periosteal osteosarcoma: a review of clinical evidence.

    PubMed

    Liu, Xin-Wei; Zi, Ying; Xiang, Liang-Bi; Han, Tian-Yu

    2015-01-01

    Periosteal osteosarcoma (PO) is a rare primary malignant bone tumor and a variant of osteosarcoma. It is a surface lesion without evidence of medullary involvement. The radiologic appearance of periosteal osteosarcoma is a broad-based surface soft-tissue mass that causes extrinsic erosion of thickened underlying diaphyseal cortex and perpendicular periosteal reaction extending into the soft-tissue component. The tumour presents as non-homogeneous masses of speculated osteoid matrix progressively denser from the periphery to their cortical base. The average age is around 28 and the most common location is the proximal third of the femur; with all the lesions diaphyseal in location. The treatment usually indicated is amputation, but in selected cases, radical segmental resection is appropriate. Long-term disease-free survival is possible after resection of the local recurrence. Limb-salvage therapy seems to offer survival equivalent to amputation, and there does not seem to be a substantial risk of late recurrence, dedifferentiation, or disease progression. The current review also highlights on various rare occurrences of periosteal osteosarcoma including the one of calcaneum, fifth metatarsal, mandible cranium, jaws, clavicle, maxilla, sphenoid bone with extensive periosteal extension, metacarpal in a paediatric age group and bilateral metachronous periosteal osteosarcoma. Recent findings relating to genetic factors governing the pathogenesis of PO is also presented.

  11. Clinical review: Checklists - translating evidence into practice

    PubMed Central

    2009-01-01

    Checklists are common tools used in many industries. Unfortunately, their adoption in the field of medicine has been limited to equipment operations or part of specific algorithms. Yet they have tremendous potential to improve patient outcomes by democratizing knowledge and helping ensure that all patients receive evidence-based best practices and safe high-quality care. Checklist adoption has been slowed by a variety of factors, including provider resistance, delays in knowledge dissemination and integration, limited methodology to guide development and maintenance, and lack of effective technical strategies to make them available and easy to use. In this article, we explore some of the principles and possible strategies to further develop and encourage the implementation of checklists into medical practice. We describe different types of checklists using examples and explore the benefits they offer to improve care. We suggest methods to create checklists and offer suggestions for how we might apply them, using some examples from our own experience, and finally, offer some possible directions for future research. PMID:20064195

  12. [Evidence-Based Knowledge Translation: From Scientific Evidence to Clinical Nursing Practice].

    PubMed

    Chen, Kee-Hsin; Kao, Ching-Chiu; Chen, Chiehfeng

    2016-12-01

    In 1992, Gordon Guyatt coined the term "evidence-based medicine", which has since attracted worldwide attention. In 2007, the Institute of Medicine's Roundtable on Evidence-Based Medicine set the goal that 90% of clinical decisions would be supported by accurate, timely, and up-to-date clinical information and would reflect the best available evidence by 2020. However, the chasm between knowing and doing remains palpable. In 2000, the Canadian Institute of Health Research applied the term "knowledge translation" to describe the bridge that is necessary to cross the gap between research knowledge and clinical practice. The present paper outlines the conceptual framework, barriers, and promotion strategies for evidence-based knowledge translation and shares clinical experience related to overcoming the seven layers of leakage (aware, accepted, applicable, able, acted on, agreed, and adhered to). We hope that this paper can enhance the public well-being and strengthen the future health care system.

  13. Ice core evidence for a recent increase in snow accumulation in coastal Dronning Maud Land, Antarctica

    NASA Astrophysics Data System (ADS)

    Philippe, Morgane; Tison, Jean-Louis; Fjøsne, Karen; Hubbard, Bryn; Kjær, Helle Astrid; Lenaerts, Jan; Sheldon, Simon Geoffrey; De Bondt, Kevin; Claeys, Philippe; Pattyn, Frank

    2016-04-01

    Ice cores provide temporal records of snow accumulation, a crucial component of Antarctic mass balance. Coastal areas are particularly under-represented in such records, despite their relatively high and sensitive accumulation rates. Here we present records from a 120 m ice core drilled on Derwael Ice Rise, coastal Dronning Maud Land (DML), East Antarctica in 2012. We date the ice core bottom back to 1745 ± 2 AD. δ18O and δD stratigraphy is supplemented by discontinuous major ion profiles, and verified independently by electrical conductivity measurements (ECM) to detect volcanic horizons. The resulting annual layer history is combined with the core density profile to calculate accumulation history, corrected for the influence of ice deformation. The mean long-term accumulation is 0.425 ± 0.035 m water equivalent (w.e.) a-1 (average corrected value). Reconstructed annual accumulation rates show an increase from 1955 onward to a mean value of 0.61 ± 0.02 m w.e. a-1 between 1955 and 2012. This trend is compared to other reported accumulation data in Antarctica, generally showing a high spatial variability. Applying the Community Earth System Model demonstrated that sea ice and atmosphere patterns largely explain the accumulation variability. This is the first and longest record from a coastal ice core in East Antarctica showing a steady increase during the 20th and 21st centuries, thereby confirming modelling predictions.

  14. 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.

  15. Evidence for GABA-Induced Systemic GABA Accumulation in Arabidopsis upon Wounding

    PubMed Central

    Scholz, Sandra S.; Malabarba, Jaiana; Reichelt, Michael; Heyer, Monika; Ludewig, Frank; Mithöfer, Axel

    2017-01-01

    The non-proteinogenic amino acid γ-aminobutyric acid (GABA) is present in all plant species analyzed so far. Its synthesis is stimulated by either acidic conditions occurring after tissue disruption or higher cytosolic calcium level. In mammals, GABA acts as inhibitory neurotransmitter but its function in plants is still not well understood. Besides its involvement in abiotic stress resistance, GABA has a role in the jasmonate-independent defense against invertebrate pests. While the biochemical basis for GABA accumulation in wounded leaves is obvious, the underlying mechanisms for wounding-induced GABA accumulation in systemic leaves remained unclear. Here, the Arabidopsis thaliana knock-out mutant lines pop2-5, unable to degrade GABA, and tpc1-2, lacking a wounding-induced systemic cytosolic calcium elevation, were employed for a comprehensive investigation of systemic GABA accumulation. A wounding-induced systemic GABA accumulation was detected in tpc1-2 plants demonstrating that an increased calcium level was not involved. Similarly, after both mechanical wounding and Spodoptera littoralis feeding, GABA accumulation in pop2-5 plants was significantly higher in local and systemic leaves, compared to wild-type plants. Consequently, larvae feeding on these GABA-enriched mutant plants grew significantly less. Upon exogenous application of a D2-labeled GABA to wounded leaves of pop2-5 plants, its uptake but no translocation to unwounded leaves was detected. In contrast, an accumulation of endogenous GABA was observed in vascular connected systemic leaves. These results suggest that the systemic accumulation of GABA upon wounding does not depend on the translocation of GABA or on an increase in cytosolic calcium. PMID:28382046

  16. CERVICOGENIC HEADACHES: AN EVIDENCE-LED APPROACH TO CLINICAL MANAGEMENT

    PubMed Central

    2011-01-01

    Cervicogenic headache (CGH), as the diagnosis suggests, refers to a headache of cervical origin. Historically, these types of headaches were difficult to diagnose and treat because their etiology and pathophysiology was not well-understood. Even today, management of a CGH remains challenging for sports rehabilitation specialists. The purpose of this clinical suggestion is to review the literature on CGH and develop an evidence-led approach to assessment and clinical management of CGH. PMID:22034615

  17. Blood pressure lowering in acute phase of stroke: latest evidence and clinical implications

    PubMed Central

    Patarroyo, Sully Xiomara Fuentes

    2012-01-01

    Persistent controversy exists as to whether there are worthwhile beneficial effects of early, rapid lowering of elevated blood pressure (BP) in acute stroke. Elevated BP or ‘hypertension’ (i.e. systolic >140 mmHg) is common in stroke, especially in patients with pre-existing hypertension and large strokes, due to variable ‘autonomic stress’ and raised intracranial pressure. While positive associations between BP levels and poor outcomes are evident across a range of studies, very low BP levels and large reductions in BP have also been shown to predict death and dependence, more so for ischaemic stroke (IS) than intracerebral haemorrhage (ICH). Accumulating evidence indicates that early BP lowering can reduce haematoma expansion in ICH, but there is uncertainty over whether this translates into improved clinical outcomes, particularly since such an effect was not evident from haemostatic therapy in clinical trials. Guidelines generally recommend control of high systolic BP (>180 mmHg), but recent evidence indicates that even more modest elevation (>140 mmHg) increases risks of cerebral oedema and haemorrhagic transformation following thrombolysis in IS. Thus, any potential benefits of rapid BP lowering in acute stroke, particularly in IS, must be balanced against the potential risks of worsening cerebral ischaemia from altered autoregulation/perfusion. This paper explores current knowledge regarding the management of hypertension in acute stroke and introduces ongoing clinical trials aimed at resolving such a critical issue in the care of patients with acute stroke. PMID:23342232

  18. Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs

    PubMed Central

    Kaufman, Amy L.; Spitz, Jared; Jacobs, Michael; Sorrentino, Matthew; Yuen, Shennin; Danahey, Keith; Saner, Donald; Klein, Teri E.; Altman, Russ B.; Ratain, Mark J.; O’Donnell, Peter H.

    2015-01-01

    Objective To comprehensively assess the pharmacogenomic evidence of routinely-used drugs for clinical utility. Methods From January 2, 2011 to May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methodology, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation. Results Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%) representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were found recommended for clinical implementation using AGREE, with average overall quality scores of 5.18 (out of 7.0; range 3.67 to 7.0; SD 0.91). Drug guidelines had highest scores in AGREE domain 1 (Scope) (average 91.9 out of 100; SD 6.1), and moderate but still robust scores in domain 3 (Rigour) (average 73.1; SD 11.1), domain 4 (Clarity) (average 67.8; SD 12.5), and domain 5 (Applicability) (average 65.8; SD 10). The drugs clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Eight of the 10 most commonly-prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information. Conclusions Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted. PMID:26046407

  19. 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.

  20. Finding the best scientific evidence to support clinical practice.

    PubMed

    Carneiro, António Vaz

    2004-06-01

    The role of science in clinical practice is nowadays fundamental. The constant publication of studies and clinical trials provides evidence of good quality that can be used by the clinician as a basis for medical decision-making, even in a context of uncertainty and risk. Valid and relevant information can help solve the problems of clinical knowledge in practice. The main question is then how practicing clinicians can learn about the innovations and acquire the recent information that can help them to change their practice for the better. The volume of medical literature is enormous and constantly growing, and it is difficult to manage. The increasing availability of secondary data sources for daily patient care provides practical and rapid access to all this information, enabling improvements in the quality of care. In this paper we present and discuss a set of modern and high-quality instruments to obtain useful information for clinical practice.

  1. Effect of Chlorhexidine with Fluoride Mouthrinse on Plaque Accumulation, Plaque pH - A Double Blind Parallel Randomized Clinical Trial

    PubMed Central

    Saha, Sabyasachi; Singh, Sanjay

    2016-01-01

    Introduction Mouthwashes are important means used in chemical control of dental plaque. There is strong evidence suggestive of better effectiveness, when fluoride is added to chlorhexidine mouthwash. Aim To assess the anti-plaque efficacy of Chlorhexidine combined with Fluoride mouthwash and to measure its impact on plaque accumulation and on plaque pH. Materials and Methods Initially 100 subjects were screened. A double blind, parallel randomized clinical trial was conducted on 30 subjects after applying inclusion and exclusion criteria. Other independent variables were matched before randomly allocating them in three groups: Group A-Chlorhexidine as positive control, Group B-Chlorhexidine + Fluoride as test group and Group C- Distilled water as negative control. Oral prophylaxis of participants was done before onset of the study. Plaque pH was assessed before and immediately after rinsing at 0, 5 and 10 minutes interval and after 7 days with digital pH electrode (pHepR pH meter, Hanna Instruments R10285) and accumulation of plaque was recorded by Turesky et al., modification of Quigley Hein Plaque Index (1970). ANOVA test was used for statistical analysis. Results Although there was a statistically significant reduction in mean plaque scores from baseline to seven days in both Groups A and B, Group B showed better anti-plaque efficacy . Almost equal drop in plaque pH was seen for both the groups at 5 and 10 minutes. Conclusion Better anti-plaque efficacy was observed in Group B (Chlorhexidine and Fluoride combination) with minimum variation of plaque pH. PMID:27630956

  2. Experimental evidence of zone-center optical phonon softening by accumulating holes in thin Ge

    SciTech Connect

    Kabuyanagi, Shoichi; Nishimura, Tomonori; Yajima, Takeaki; Toriumi, Akira

    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.

  3. 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.

  4. Response: Clinical wisdom and evidence-based medicine are complementary.

    PubMed

    De Freitas, Julian; Haque, Omar S; Gopal, Abilash A; Bursztajn, Harold J

    2012-01-01

    A long-debated question in the philosophy of health, and contingent disciplines, is the extent to which wise clinical practice ("clinical wisdom") is, or could be, compatible with empirically validated medicine ("evidence-based medicine"--EBM). Here we respond to Baum-Baicker and Sisti, who not only suggest that these two types of knowledge are divided due to their differing sources, but also that EBM can sometimes even hurt wise clinical practice. We argue that the distinction between EBM and clinical wisdom is poorly defined, unsupported by the methodology employed, and ultimately incorrect; crucial differences exist, we argue, not in the source of a particular piece of clinical knowledge, but in its dependability. In light of this subtle but fundamental revision, we explain how clinical wisdom and EBM are--by necessity--complementary, rather than in conflict. We elaborate on how recognizing this relationship can have far-reaching implications for the domains of clinical practice, medical education, and health policy.

  5. Spectroscopic evidence for a lava fountain driven by previously accumulated magmatic gas.

    PubMed

    Allard, Patrick; Burton, Mike; Muré, Filippo

    2005-01-27

    Lava fountains are spectacular continuous gas jets, propelling lava fragments to heights of several hundred metres, which occasionally occur during eruptions of low-viscosity magmas. Whether they are generated by the effervescent disruption of fast-rising bubbly melt or by the separate ascent of a bubble foam layer accumulated at depth still remains a matter of debate. No field measurement has yet allowed firm discrimination between these two models. A key insight into the origin of lava fountains may be gained by measuring the chemical composition of the driving gas phase. This composition should differ markedly depending on whether the magma degassing occurs before or during eruption. Here we report the analysis of magmatic gas during a powerful (250-600 m high) lava fountain, measured with Fourier transform infrared spectroscopy on Mount Etna, Sicily. The abundances of volcanic gas species, determined from absorption spectra of lava radiation, reveal a fountain gas having higher CO2/S and S/Cl ratios than other etnean emissions, and which cannot derive from syn-eruptive bulk degassing of Etna basalt. Instead, its composition suggests violent emptying of a gas bubble layer previously accumulated at about 1.5 km depth below the erupting crater.

  6. Clinical evidence of statin therapy in non-dyslipidemic disorders.

    PubMed

    Ferri, Nicola; Corsini, Alberto

    2014-10-01

    The clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidences have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) has begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases.

  7. 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.

  8. Optical studies of MBE-grown InN nanocolumns: Evidence of surface electron accumulation

    NASA Astrophysics Data System (ADS)

    Segura-Ruiz, J.; Garro, N.; Cantarero, A.; Denker, C.; Malindretos, J.; Rizzi, A.

    2009-03-01

    Vertically self-aligned InN nanocolumns have been investigated by means of scanning electron microscopy, Raman scattering, and photoluminescence spectroscopy. Different nanocolumn morphologies corresponding to different molecular beam epitaxy growth conditions have been studied. Raman spectra revealed strain-free nanocolumns with high crystalline quality for the full set of samples studied. Longitudinal optical modes both uncoupled and coupled to an electron plasma coexist in the Raman spectra pointing to the existence of two distinctive regions in the nanocolumn: a surface layer of degenerated electrons and a nondegenerated inner core. The characteristics of the low-temperature photoluminescence and its dependence on temperature and excitation power can be explained by a model considering localized holes recombining with degenerated electrons close to the nonpolar surface. The differences observed in the optical response of different samples showing similar crystalline quality have been attributed to the variation in the electron accumulation layer with the growth conditions.

  9. Evaluating the impacts of human capital stocks and accumulation on economic growth: some new evidence.

    PubMed

    Gemmell, N

    1996-02-01

    "Various hypotheses have been put forward in recent years concerning the contribution of human capital to economic growth. This paper argues that school enrolment rates--by far the most commonly used human capital measure in growth regressions attempting to test these hypotheses--conflate human capital stock and accumulation effects and lead to misinterpretations of the role of labour force growth. An alternative education-related human capital measure is constructed which is capable of distinguishing between stocks and flows. Applying this measure to samples of developed and less developed countries during the 1960-85 period suggests not only that there are important growth effects associated both with 'initial' stocks of, and subsequent growth in, human capital, but also that this new measure out-performs the simple school enrolment rates used in previous analyses."

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

    PubMed Central

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

    2003-01-01

    Background Research has shown that many healthcare professionals have problems with guidelines as they would prefer to be given all relevent information relevent 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 Methods Opinions elicited using a standardised questionnaire delivered either by mail or during educational or professional meetings Results 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. Conclusions 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. PMID:14693035

  11. 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

  12. 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.

  13. Towards automatic recognition of scientifically rigorous clinical research evidence.

    PubMed

    Kilicoglu, Halil; Demner-Fushman, Dina; Rindflesch, Thomas C; Wilczynski, Nancy L; Haynes, R Brian

    2009-01-01

    The growing numbers of topically relevant biomedical publications readily available due to advances in document retrieval methods pose a challenge to clinicians practicing evidence-based medicine. It is increasingly time consuming to acquire and critically appraise the available evidence. This problem could be addressed in part if methods were available to automatically recognize rigorous studies immediately applicable in a specific clinical situation. We approach the problem of recognizing studies containing useable clinical advice from retrieved topically relevant articles as a binary classification problem. The gold standard used in the development of PubMed clinical query filters forms the basis of our approach. We identify scientifically rigorous studies using supervised machine learning techniques (Naïve Bayes, support vector machine (SVM), and boosting) trained on high-level semantic features. We combine these methods using an ensemble learning method (stacking). The performance of learning methods is evaluated using precision, recall and F(1) score, in addition to area under the receiver operating characteristic (ROC) curve (AUC). Using a training set of 10,000 manually annotated MEDLINE citations, and a test set of an additional 2,000 citations, we achieve 73.7% precision and 61.5% recall in identifying rigorous, clinically relevant studies, with stacking over five feature-classifier combinations and 82.5% precision and 84.3% recall in recognizing rigorous studies with treatment focus using stacking over word + metadata feature vector. Our results demonstrate that a high quality gold standard and advanced classification methods can help clinicians acquire best evidence from the medical literature.

  14. Eye-hand coordination during a double-step task: evidence for a common stochastic accumulator.

    PubMed

    Gopal, Atul; Murthy, Aditya

    2015-09-01

    Many studies of reaching and pointing have shown significant spatial and temporal correlations between eye and hand movements. Nevertheless, it remains unclear whether these correlations are incidental, arising from common inputs (independent model); whether these correlations represent an interaction between otherwise independent eye and hand systems (interactive model); or whether these correlations arise from a single dedicated eye-hand system (common command model). Subjects were instructed to redirect gaze and pointing movements in a double-step task in an attempt to decouple eye-hand movements and causally distinguish between the three architectures. We used a drift-diffusion framework in the context of a race model, which has been previously used to explain redirect behavior for eye and hand movements separately, to predict the pattern of eye-hand decoupling. We found that the common command architecture could best explain the observed frequency of different eye and hand response patterns to the target step. A common stochastic accumulator for eye-hand coordination also predicts comparable variances, despite significant difference in the means of the eye and hand reaction time (RT) distributions, which we tested. Consistent with this prediction, we observed that the variances of the eye and hand RTs were similar, despite much larger hand RTs (∼90 ms). Moreover, changes in mean eye RTs, which also increased eye RT variance, produced a similar increase in mean and variance of the associated hand RT. Taken together, these data suggest that a dedicated circuit underlies coordinated eye-hand planning.

  15. Cancer therapy with phytochemicals: evidence from clinical studies

    PubMed Central

    Hosseini, Azar; Ghorbani, Ahmad

    2015-01-01

    Cancer is still one of the major causes of mortality in both developing and developed countries. At present, in spite of intensive interventions, a large number of patients suffer from poor prognosis. Therefore, the effort for finding new anticancer agents with better efficacy and lesser side effects has been continued. According to the traditional recommendations and experimental studies, numerous medicinal plants have been reported to have anticancer effect. Also antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects of several phytochemicals have been shown in in vitro experiments or animal studies. However, only a small number have been tested in cancerous patients and limited evidence exists for their clinical effectiveness. Also, regarding some phytochemicals, only beneficial effects on cancer-related symptoms or on quality of life have been reported and no positive results exist for their antitumor actions. This review was focused on the phytochemicals whole beneficial effects on various types of cancer have been supported by clinical trials. Based on the literature review, curcumin, green tea, resveratrol and Viscum album were the satisfactory instances of clinical evidence for supporting their anticancer effects. The main findings of these phytochemicals were also summarized and discussed. PMID:25949949

  16. Error awareness revisited: accumulation of multimodal evidence from central and autonomic nervous systems.

    PubMed

    Wessel, Jan R; Danielmeier, Claudia; Ullsperger, Markus

    2011-10-01

    The differences between erroneous actions that are consciously perceived as errors and those that go unnoticed have recently become an issue in the field of performance monitoring. In EEG studies, error awareness has been suggested to influence the error positivity (Pe) of the response-locked event-related brain potential, a positive voltage deflection prominent approximately 300 msec after error commission, whereas the preceding error-related negativity (ERN) seemed to be unaffected by error awareness. Erroneous actions, in general, have been shown to promote several changes in ongoing autonomic nervous system (ANS) activity, yet such investigations have only rarely taken into account the question of subjective error awareness. In the first part of this study, heart rate, pupillometry, and EEG were recorded during an antisaccade task to measure autonomic arousal and activity of the CNS separately for perceived and unperceived errors. Contrary to our expectations, we observed differences in both Pe and ERN with respect to subjective error awareness. This was replicated in a second experiment, using a modified version of the same task. In line with our predictions, only perceived errors provoke the previously established post-error heart rate deceleration. Also, pupil size yields a more prominent dilatory effect after an erroneous saccade, which is also significantly larger for perceived than unperceived errors. On the basis of the ERP and ANS results as well as brain-behavior correlations, we suggest a novel interpretation of the implementation and emergence of error awareness in the brain. In our framework, several systems generate input signals (e.g., ERN, sensory input, proprioception) that influence the emergence of error awareness, which is then accumulated and presumably reflected in later potentials, such as the Pe.

  17. Evidence that both genetic instability and selection contribute to the accumulation of chromosome alterations in cancer.

    PubMed

    Gorringe, Kylie L; Chin, Suet-Feung; Pharoah, Paul; Staines, Joanne M; Oliveira, Carla; Edwards, Paul A W; Caldas, Carlos

    2005-05-01

    Cancer cells contain many genetic alterations, and genetic instability may be important in tumourigenesis. We evaluated 58 breast and ovarian cancer cell lines for microsatellite instability (MSI) and chromosomal instability (CIN). MSI was identified in 3/33 breast and 5/25 ovarian cell lines, and 7/8 MSI lines showed an inactivation of mismatch repair. Average ploidy by centromeric fluorescence in situ hybridization (FISH) of MSI (n = 8, average ploidy = 2.65) and microsatellite stable (MSS; n = 7, average ploidy = 3.01) cell lines was not different, due to the presence of three aneuploid MSI lines, and two near-diploid MSS lines. However, the variability of the centromeric FISH data was different between MSI and MSS (P = 0.049). The complexity of structural chromosomal rearrangements was not different between MSI and MSS. Thus, MSI and numerical CIN are not mutually exclusive, and structural CIN occurs independently of MSI or numerical CIN. Dynamic genetic instability was evaluated in three cell lines-MSI diploid (MT-3), MSS diploid (SUM159) and MSS aneuploid (MT-1). Ten clones of each of these cell lines were analysed by centromeric FISH and six-colour chromosome painting. The variation in chromosome number was different among all three cell lines (P < 0.001). MT-3 appeared numerically constant (94% of centromeric FISH signals matched the mode). SUM159 was 88% constant; however, 7% of cells had duplicated chromosomes. MT-1 was 82% constant; most changes were chromosomal losses. The six-colour FISH data showed that SUM159 had more stable structural chromosomal alterations (e.g. chromosomal translocations) compared with MT-3 and MT-1, but had no increase in unstable changes (e.g. chromatid breaks) when compared with MT-3. MT-1 had fewer unstable changes than both MT-3 and SUM159. These data suggest that numerical CIN may contribute to aneuploidy, but that selection plays an important role, particularly for the accumulation of structural chromosomal changes.

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

    PubMed

    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.

  19. Spirulina in clinical practice: evidence-based human applications.

    PubMed

    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.

  20. 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.

  1. 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.

  2. 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.

  3. Challenges in Acute Heart Failure Clinical Management: Optimizing Care Despite Incomplete Evidence and Imperfect Drugs

    PubMed Central

    Maisel, Alan S.; Storrow, Alan B.

    2015-01-01

    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. PMID:25679083

  4. Accumulating Evidence Supports a Taste Component for Free Fatty Acids in Humans

    PubMed Central

    Mattes, Richard D.

    2011-01-01

    The requisite criteria for what constitutes a taste primary have not been established. Recent advances in understanding of the mechanisms and functions of taste have prompted suggestions for an expanded list of unique taste sensations, including fat, or more specifically, free fatty acids (FFA). A set of criteria are proposed here and the data related to FFA are reviewed on each point. It is concluded that the data are moderate to strong that there are: A) adaptive advantages to FFA detection in the oral cavity; B) adequate concentrations of FFA to serve as taste stimuli; C) multiple complimentary putative FFA receptors on taste cells; D) signals generated by FFA that are conveyed by gustatory nerves; E) sensations generated by FFA that can be detected and scaled by psychophysical methods in humans when non-gustatory cues are masked; and F) physiological responses to oral fat/FFA exposure. On no point is there strong evidence challenging these observations. The reviewed findings are suggestive, albeit not definitive, that there is a taste component for FFA. PMID:21557960

  5. Accumulating evidence for increased velocity of airway smooth muscle shortening in asthmatic airway hyperresponsiveness.

    PubMed

    Ijpma, Gijs; Matusovsky, Oleg; Lauzon, Anne-Marie

    2012-01-01

    It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

  6. Toward clinical scholarship: promoting evidence-based practice in the clinical setting.

    PubMed

    Mohide, E Ann; Coker, Esther

    2005-01-01

    Organizational interventions are being suggested to increase the rate of quality research dissemination and uptake. This article describes how one tertiary institution is using an evidence-based nursing (EBN) committee as an organizational strategy to shift its nursing culture toward clinical scholarship. A number of approaches and activities that have stimulated the movement toward evidence-based practice (EBP) are examined: organizational commitment to EBP, strategic positioning of the EBN committee within nursing's administrative structure, articulation of a mission, conceptualization of a model for EBN practice, learning on the job, selection and adoption of an evidence-based model for implementing change, marketing for a change in culture toward clinical scholarship, and other selected examples of projects undertaken by the committee. Action-oriented principles associated with committee experiences are related to the approaches and activities.

  7. 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.

  8. 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.

  9. Experimental and Theoretical Evidence for Diastereomer- and Enantiomer-Specific Accumulation and Biotransformation of HBCD in Maize Roots.

    PubMed

    Huang, Honglin; Zhang, Shuzhen; Lv, Jitao; Wen, Bei; Wang, Sen; Wu, Tong

    2016-11-15

    Diastereomer- and enantiomer-specific accumulation and biotransformation of hexabromocyclododecane (HBCD) in maize (Zea mays L.) were investigated. Molecular interactions of HBCD with plant enzymes were further characterized by homology modeling combined with molecular docking. The (-)α-, (-)β-, and (+)γ-HBCD enantiomers accumulated to levels in maize significantly higher than those of their corresponding enantiomers. Bioisomerization from (+)/(-)-β- and γ-HBCDs to (-)α-HBCD was frequently observed, and (-)γ-HBCD was most easily converted, with bioisomerization efficiency of 90.5 ± 8.2%. Mono- and dihydroxyl HBCDs, debrominated metabolites including pentabromocyclododecene (PBCDe) and tetrabromocyclododecene (TBCDe), and HBCD-GSH adducts were detected in maize roots. Patterns of hydroxylated and debrominated metabolites were significantly different among HBCD diastereomers and enantiomers. Three pairs of HBCD enantiomers were selectively bound into the active sites and interacted with specific residues of maize enzymes CYP71C3v2 and GST31. (+)α-, (-)β-, and (-)γ-HBCDs preferentially bound to CYP71C3v2, whereas (-)α-, (-)β-, and (+)γ-HBCDs had strong affinities to GST31, consistent with experimental observations that (+)α-, (-)β-, and (-)γ-HBCDs were more easily hydroxylated, and (-)α-, (-)β-, and (+)γ-HBCDs were more easily isomerized and debrominated in maize compared to their corresponding enantiomers. This study for the first time provided both experimental and theoretical evidence for stereospecific behaviors of HBCD in plants.

  10. Evidence for the use of organic carbon as the sorbing matrix in the modeling of PCB accumulation in phytoplankton

    SciTech Connect

    Skoglung, R.S.; Swackhamer, D.L.

    1999-05-01

    This report presents empirical evidence for the use of organic carbon as the sorbing matrix in the kinetic modeling of PCB accumulation in phytoplankton. A kinetic-based model was used to predict congener-specific bioaccumulation factors of PCBs in phytoplankton samples collected from Green Bay, Lake Michigan. These values were compared to the measured bioaccumulation factors, and the sum of the residuals was used to evaluate the model`s predictive quality. The sorbing matrix fraction (F{sub M}) that minimized the sum of residuals of the model was then solved by iteration. The appropriateness of using dry weight, organic carbon fraction, or lipid fractions as the sorbing matrix fraction was determined by measuring their correlation to the optimum F{sub M}. It was determined that the F{sub M} correlated best with the organic carbon fraction, and this correlation appeared to be independent of both the spatial and seasonal differences of the field samples.

  11. Curcumin and insulin resistance-Molecular targets and clinical evidences.

    PubMed

    Jiménez-Osorio, Angélica Saraí; Monroy, Adriana; Alavez, Silvestre

    2016-11-12

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016.

  12. 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

  13. 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.

  14. Anemia, Heart Failure and Evidence-Based Clinical management

    PubMed Central

    Pereira, Camila Alves; Roscani, Meliza Goi; Zanati, Silméia Garcia; Matsubara, Beatriz Bojikian

    2013-01-01

    Anemia is a prevalent comorbidity and marker of a poorer prognosis in patients with heart failure (HF). Its clinical relevance, as well as its pathophysiology and the clinical management of these patients are important subjects in the specialized literature. In the present review, we describe the current concepts on the pathophysiology of anemia in HF, its diagnostic criteria, and the recommendations for iron supplementation. Also, we make a critical analysis of the major studies showing evidences on the benefits of this supplementation. The four main components of anemia are addressed: chronic disease, dilutional, "renal" and malabsorption. In patients with HF, the diagnostic criteria are the same as those used in the general population: serum ferritin levels lower than 30 mcg/L in patients without kidney diseases and lower than 100 mcg/L or serum ferritin levels between 100-299 mcg/L with transferring saturation lower than 20% in patients with chronic kidney diseases. Finally, the therapeutic possibilities for anemia in this specific patient population are discussed. PMID:23917508

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Activity in inferior parietal and medial prefrontal cortex signals the accumulation of evidence in a probability learning task.

    PubMed

    d'Acremont, Mathieu; Fornari, Eleonora; Bossaerts, Peter

    2013-01-01

    In an uncertain environment, probabilities are key to predicting future events and making adaptive choices. However, little is known about how humans learn such probabilities and where and how they are encoded in the brain, especially when they concern more than two outcomes. During functional magnetic resonance imaging (fMRI), young adults learned the probabilities of uncertain stimuli through repetitive sampling. Stimuli represented payoffs and participants had to predict their occurrence to maximize their earnings. Choices indicated loss and risk aversion but unbiased estimation of probabilities. BOLD response in medial prefrontal cortex and angular gyri increased linearly with the probability of the currently observed stimulus, untainted by its value. Connectivity analyses during rest and task revealed that these regions belonged to the default mode network. The activation of past outcomes in memory is evoked as a possible mechanism to explain the engagement of the default mode network in probability learning. A BOLD response relating to value was detected only at decision time, mainly in striatum. It is concluded that activity in inferior parietal and medial prefrontal cortex reflects the amount of evidence accumulated in favor of competing and uncertain outcomes.

  20. Evidence-based review of clinical studies on pulpotomy.

    PubMed

    2009-08-01

    Although pulpotomy procedures have a long history of clinical application, comparatively few dental clinical trials have evaluated this treatment approach. In this section, we provide an analysis of recent clinical studies evaluating pulpotomy procedures in dental patients.

  1. BEHAVIORAL OUTCOMES OF MONOAMINE OXIDASE DEFICIENCY: PRECLINICAL AND CLINICAL EVIDENCE

    PubMed Central

    Bortolato, Marco; Shih, Jean C.

    2012-01-01

    Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity—due to either genetic or environmental factors—can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson’s disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene × environment interactions in the vulnerability to several mental disorders. PMID:21971001

  2. Selenium and clinical trials: new therapeutic evidence for multiple diseases.

    PubMed

    Sanmartin, C; Plano, D; Font, M; Palop, J A

    2011-01-01

    The understanding of the essential role of selenium (Se) in human health has increased substantially in recent decades. Micronutrient deficiencies are very common in the general population and may be even more common in patients with different pathologies due to genetic or environmental causes and prescription drug use. Selenium is used by people in the prevention and/or treatment of different disorders including cardiovascular disease, osteoarthritis, rheumatoid arthritis, hypothyroidism, stroke, atherosclerosis, cancer susceptibility and treatment, HIV, AIDS, neuronal diseases such as Alzheimer or amyotrophic lateral sclerosis, pancreatitis, depression, and diabetes amongst others. Several mechanisms have been suggested to mediate the biological effects of Se and these include antioxidant defence systems, synthesis and stability of metabolites that act as intermediates implicated in diverse selenoproteins expression pathways oxidative metabolism, immune system modulation, DNA intercalators, kinase regulation, enzymatic cofactor, and gene expression. A number of clinical trials in recent years have provided convincing evidence of the central role of this element, either alone or in combination with other micronutrients or antioxidants, in the prevention and treatment of multiple diseases. Based on these studies this review focuses on the advances made so far in the study of mechanisms and applications of selenium compounds that could be suitable for chronic diseases.

  3. Evidence that accumulation of mutants in a biofilm reflects natural selection rather than stress-induced adaptive mutation.

    PubMed

    Banas, Jeffrey A; Miller, Justin D; Fuschino, Meghan E; Hazlett, Karsten R O; Toyofuku, Wendy; Porter, Kristen A; Reutzel, Sarah B; Florczyk, Matthew A; McDonough, Kathleen A; Michalek, Suzanne M

    2007-01-01

    The accumulation of mutant genotypes within a biofilm evokes the controversy over whether the biofilm environment induces adaptive mutation or whether the accumulation can be explained by natural selection. A comparison of the virulence of two strains of the dental pathogen Streptococcus mutans showed that rats infected with one of the strains accumulated a high proportion (average, 22%) of organisms that had undergone a deletion between two contiguous and highly homologous genes. To determine if the accumulation of deletion mutants was due to selection or to an increased mutation rate, accumulations of deletion mutants within in vitro planktonic and biofilm cultures and within rats inoculated with various proportions of deletion organisms were quantified. We report here that natural selection was the primary force behind the accumulation of the deletion mutants.

  4. Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them.

    PubMed

    Garattini, Silvio; Jakobsen, Janus C; Wetterslev, Jørn; Bertelé, Vittorio; Banzi, Rita; Rath, Ana; Neugebauer, Edmund A M; Laville, Martine; Masson, Yvonne; Hivert, Virginie; Eikermann, Michaela; Aydin, Burc; Ngwabyt, Sandra; Martinho, Cecilia; Gerardi, Chiara; Szmigielski, Cezary A; Demotes-Mainard, Jacques; Gluud, Christian

    2016-07-01

    Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them. Pertinent literature was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment represent the highest level of evidence. Even though systematic reviews are trust worthier than other types of evidence, all levels of the evidence hierarchy are under threats from systematic errors (bias); design errors (abuse of surrogate outcomes, composite outcomes, etc.); and random errors (play of chance). Clinical research infrastructures may help in providing larger and better conducted trials. Trial Sequential Analysis may help in deciding when there is sufficient evidence in meta-analyses. If threats to the validity of clinical research are carefully considered and minimised, research results will be more valid and this will benefit patients and heath care systems.

  5. Focus on the Novel Cardiovascular Drug LZC696: from Evidence to Clinical Consideration.

    PubMed

    Lin, L M; Wu, Y; Wu, M F; Lin, J X

    2016-12-01

    LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement. Powerful evidence including PARAMETER and PRARDIGM-HF trials have shown that LCZ696 outperforms RAAS inhibition in treating patients with hypertension and heart failure with reduced ejection fraction (HFrEF), and is well tolerated. In addition, accumulating evidence also suggests its potential use in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), post-myocardium infarction (post-MI) and stroke. Both the FDA and CHMP have approved LCZ696 for treatment of HFrEF. Despite all this, some special issues (e.g. use in specific subgroups, adverse events, contraindications and cost-effectiveness analysis) should be considered before its implementation in clinical practice.

  6. Serum nitric oxide metabolite as a biomarker of visceral fat accumulation: Clinical significance of measurement for nitrate/nitrite

    PubMed Central

    Fujita, Koji; Wada, Koichiro; Nozaki, Yuichi; Yoneda, Masato; Endo, Hiroki; Takahashi, Hirokazu; Kirikoshi, Hiroyuki; Inamori, Masahiko; Kobayashi, Noritoshi; Kubota, Kensuke; Saito, Satoru; Nakajima, Atsushi

    2011-01-01

    Summary Background A visceral fat area of more than 100 cm2 as measured by computed tomography (CT) at the umbilical level has been included as a criterion for obesity in all the proposed criteria for metabolic syndrome. However, CT cannot be used frequently because of radiation exposure. We evaluated the usefulness of measurement of the serum levels of nitric oxide (NO), instead of CT and the waist circumference, as a marker of abdominal visceral fat accumulation. Material/Methods The study was carried out in 80 subjects. The serum levels of NO metabolites (nitrate/nitrite) were measured using the Griess reagent. Results Simple and multiple regression analysis revealed that the serum levels of NO metabolites showed the greatest degree of correlation with the visceral fat area (r=0.743, p<0.0001), and corresponded to a visceral fat area of 100 cm2, as determined using the ROC curve, was 21.0 μmol/ml (sensitivity 88%, specificity 82%); this method was more sensitive than the waist circumference for evaluation of the visceral fat accumulation. Conclusions Measurement of the serum levels of NO metabolites may be a simple, safe, convenient and reliable method for the evaluation of visceral fat accumulation in clinical diagnostic screening. PMID:21358598

  7. [Evidence from large clinical trials for Japanese hypertensive patients].

    PubMed

    Okura, Takafumi; Higaki, Jitsuo

    2011-11-01

    Large-scale clinical trials for the hypertensive patients have been carried out in Japan. Double-blind, placebo-controlled large clinical trials in Europe and USA showed that antihypertensive drugs prevented cardiovascular disease. Recently large clinical trials carried out in Japan. These clinical trials have shown that the onset rate of the heart vascular disease in Japanese hypertensive patients, the factor which influenced the onset of the cardiovascular disease, and the suppressant effect of cardiovascular disease of different antihypertensive drug class.

  8. HDL and Atherosclerosis Regression: Evidence from Pre-clinical and Clinical Studies

    PubMed Central

    Feig, Jonathan E.; Hewing, Bernd; Smith, Jonathan D.; Hazen, Stanley L.; Fisher, Edward A.

    2014-01-01

    High density lipoprotein particles (HDL) transport, among other molecules, cholesterol (HDL-C). In epidemiologic studies, plasma HDL-C levels have an inverse relationship to the risk of atherosclerotic cardiovascular disease (CVD). It has been assumed that this reflects the protective functions of HDL, which include their ability to promote cholesterol efflux. Yet, a number of recent pharmacological and genetic studies have failed to demonstrate that increased plasma levels of HDL-C resulted in decreased CVD risk, giving rise to a controversy over whether plasma levels of HDL-C reflect HDL function, or that HDL is even as protective as assumed. On balance, the evidence from pre-clinical and (limited) clinical studies show that HDL can promote the regression of atherosclerosis when the levels of functional particles are increased from endogenous or exogenous sources. The data show that regression results from a combination of reduced plaque lipid and macrophage contents, as well as from a reduction in its inflammatory state. While more research will be needed on basic mechanisms and to establish that these changes translate clinically to reduced CVD events, that HDL can regress plaques suggests that the recent trial failures do not eliminate HDL from consideration as an atheroprotective agent, but emphasizes the important distinction between HDL function and plasma levels of HDL-C. PMID:24385513

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

    PubMed Central

    Hajjaj, FM; Salek, MS; Basra, MKA; Finlay, AY

    2010-01-01

    Summary 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. PMID:20436026

  10. [A new form of hereditary neurodegeneration with brain iron accumulation: clinical and molecular-genetic characteristics].

    PubMed

    Zakharova, E Yu; Rudenskaya, G E

    2014-01-01

    Neurodegeneration with brain iron accumulation, type 4 (NBIA4, or MPAN) is an autosomal recessive disease produced by С19org12 mutations. NBIA group includes also most common NBIA1 or PKAN (formerly Hallervorden-Spatz disease) NBIA2 or PLAN, and few others. Common NBIA features are onset in childhood or adolescence, progressive movement disorders (spasticity, dystonia, parkinsonism), dysarthria, optic atrophy, cognitive and neuropsychiatric disorders, and MRI picture of iron accumulation in globus pallidum and substantia nigra. Though only recently recognized, NBIA4 was reported in many populations and seems to be not rare. We diagnosed NBIA4 in three non-consanguineous Russian families. Case 1, 19-year-old female, had slowly progressing leg spasticity since 12 yrs, moderate dystonia in neck, hands and feet since 17-18 yrs, optic atrophy detected in 18 yrs and mild cognitive impairment; MRI was normal in 14 yrs, but in 17 yrs showed typical NBIA signs. Case 2, 16-year-old male, had slowly progressing spasticity, dystonia, ataxia and mild dementia since 11-12 yrs; MRI was normal up to 16 yrs when NBIA signs appeared; optic atrophy was seen at the same age. In both patients homozygosity for C19orf12 mutation с.204_214del11 (Gly69ArgfsX10) was detected. The mutation is most common in Polish and other East European populations. Case 3 is atypical in several aspects. The patient is 35-year-old female with Usher syndrome, autosomal recessive disease including congenital sensorineural deafness and retinitis pigmentosa; her junior sister is also affected. MRI was performed because of headaches and unexpectedly detected NBIA picture (MRI in the sister could not be performed due to technical contra-indications). No NBIA symptoms were seen in 35 and in 36.5 yrs. Heterozygosity for the same C19orf2 mutation Gly69ArgfsX10 was detected in the patient, but not in the sister; allelic mutation was not found by now. We consider the case as co-existence of two independent disorders

  11. 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

  12. [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.

  13. 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.

  14. Nurse practitioner clinical decision-making and evidence-based practice.

    PubMed

    Vincent, Deborah; Hastings-Tolsma, Marie; Gephart, Sheila; Alfonzo, Paige M

    2015-05-15

    Evidence-based practice is key to improving patient outcomes but can be challenging for busy nurse practitioners to implement. This article describes the process of critically appraising evidence for use in clinical practice and offers strategies for implementing evidence-based innovations and disseminating the findings.

  15. Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration.

    PubMed

    Thomas, Madhavi; Hayflick, Susan J; Jankovic, Joseph

    2004-01-01

    Hallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3-p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase-associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 (PANK2) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult-onset patients whereas dystonia seems more frequent in the earlier-onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome.

  16. Do Child Development Accounts Promote Account Holding, Saving, and Asset Accumulation for Children's Future? Evidence from a Statewide Randomized Experiment

    ERIC Educational Resources Information Center

    Nam, Yunju; Kim, Youngmi; Clancy, Margaret; Zager, Robert; Sherraden, Michael

    2013-01-01

    This study examines the impacts of Child Development Accounts (CDAs) on account holding, saving, and asset accumulation for children, using data from the SEED for Oklahoma Kids experiment (SEED OK). SEED OK, a policy test of universal and progressive CDAs, provides a 529 college savings plan account to every infant in the treatment group with…

  17. Anti-RANKL therapy for bone tumours: Basic, pre-clinical and clinical evidences

    PubMed Central

    Heymann, Dominique

    2012-01-01

    Bone remodelling is related to coordinated phases of bone resorption and bone apposition allowing the maintenance of bone integrity, the phosphocalcic homoeostasis all along the life and consequently the bone adaptation to mechanical constraints or/and to endocrine fluctuations. Unfortunately, bone is a frequent site of tumour development originated from bone cell lineages (primary bone tumours: bone sarcomas) or from nonosseous origins (bone metastases: carcinomas). These tumour cells disrupt the balance between osteoblast and osteoclast activities resulting in a disturbed bone remodelling weakening the bone tissue, in a strongly altered bone microenvironment and consequently facilitating the tumour growth. At the early stage of tumour development, osteoclast differentiation and recruitment of mature osteoclasts are strongly activated resulting in a strong bone matrix degradation and release of numerous growth factors initially stored into this organic/calcified matrix. In turn these soluble factors stimulate the proliferation of tumour cells and exacerbate their migration and their ability to initiate metastases. Because Receptor Activator of NFκB Ligand (RANKL) is absolutely required for in vivo osteoclastogenesis, its role in the bone tumour growth has been immediately pointed out and has consequently allowed the development of new targeted therapies of these malignant diseases. The present review summarises the role of RANKL in the bone tumour microenvironment, the most recent pre-clinical and clinical evidences of its targeting in bone metastases and bone sarcomas. The following sections position RANKL targeted therapy among the other anti-resorptive therapies available and underline the future directions which are currently under investigations. PMID:26909248

  18. Evidence for accumulation of Synechococcus elongatus (Cyanobacteria: Cyanophyceae) in the tissues of the oyster Crassostrea gigas (Mollusca: Bivalvia).

    PubMed

    Avila-Poveda, Omar Hernando; Torres-Ariño, Alejandra; Girón-Cruz, Diego Ademir; Cuevas-Aguirre, Angel

    2014-10-01

    Cyanobacteria appear to have direct relations with mollusks in several aspects. This is the first time, distinguishing Gram-negative cyanoprokaryotic Synechococcus elongatus as bright yellow-gold autofluorescence by Lillie's and Hiss' staining methods on paraffin-embedded tissues of Crassostrea gigas. Three diets: cyanoprokaryotes, cyanoprokaryotes with microalgae, and only microalgae were evaluated. Cyanoprokaryotes were intact, densely bundled, and immersed in the cytosol of the digestive gland, connective tissue, mantle, and gonad of C. gigas, revealing an accumulation systemic without tissue damage observed by histology. Unexpectedly, cyanoprokaryotes were slightly most accumulated with microalgae diet by each of the tissues of the C. gigas than with any other diets. Cyanoprokaryotes tend to be in mean slightly higher in the digestive gland than in any other tissues respectively for each diet, although these values are closely similar to connective tissue. A possible order of exposure of the oyster tissues to accumulation of cyanoprokaryotes was digestive gland, connective tissue, mantle, and gonad. Thereby, the digestive gland could be the major target tissue for the accumulation. Our observations provide a valuable insight regarding the ability of cyanoprokaryotes to penetrate, spread, and remain inside the oyster tissues, suggesting for S. elongatus: (1) a pre-accumulation in oyster tissues from the natural environment, (2) a phagocytosis and/or endocytosis process rather than ingestion and extracellular digestion, (3) an apparent cellular division in the cytosol of oyster tissues, (4) an apparent inter-tissue movement, and (5) a possible endosymbiosis between C. gigas and S. elongatus. Hereby, it is possible that S. elongatus have a well-developed host-endobiont relationship with oysters, and thereby support future work toward a description of the escape and spreading mechanisms of S. elongatus inside the tissues of mollusks, and put forward questions as

  19. Clinical and experimental evidence of supernormal excitability and conduction.

    PubMed

    Elizari, Marcelo V; Schmidberg, Jorge; Atienza, Augusto; Paredes, Diego V; Chiale, Pablo A

    2014-08-01

    True supernormality of excitability and conduction has been demonstrated in normal Purkinje fibers in in vitro studies. In the clinical setting, supernormality of conduction is manifested better than expected. This phenomenon is much more common than previously thought, particularly in the presence of certain clinical conditions. If a careful scanning of the cardiac cycle is performed on all patients with intermittent bundle branch block and second degree or advanced infranodal AV block, accessory pathways and mulfunctioning pacemakers, it is anticipated that a much larger amount of supernormal excitability and conduction will be unmasked.

  20. Clinical and Experimental Evidence of Supernormal Excitability and Conduction

    PubMed Central

    Elizari, Marcelo V; Schmidberg, Jorge; Atienza, Augusto; Paredes, Diego V; Chiale, Pablo A

    2014-01-01

    True supernormality of excitability and conduction has been demonstrated in normal Purkinje fibers in in vitro studies. In the clinical setting, supernormality of conduction is manifested better than expected. This phenomenon is much more common than previously thought, particularly in the presence of certain clinical conditions. If a careful scanning of the cardiac cycle is performed on all patients with intermittent bundle branch block and second degree or advanced infranodal AV block, accessory pathways and mulfunctioning pacemakers, it is anticipated that a much larger amount of supernormal excitability and conduction will be unmasked. PMID:24827801

  1. Towards automated calculation of evidence-based clinical scores

    PubMed Central

    Aakre, Christopher A; Dziadzko, Mikhail A; Herasevich, Vitaly

    2017-01-01

    AIM To determine clinical scores important for automated calculation in the inpatient setting. METHODS A modified Delphi methodology was used to create consensus of important clinical scores for inpatient practice. A list of 176 externally validated clinical scores were identified from freely available internet-based services frequently used by clinicians. Scores were categorized based on pertinent specialty and a customized survey was created for each clinician specialty group. Clinicians were asked to rank each score based on importance of automated calculation to their clinical practice in three categories - “not important”, “nice to have”, or “very important”. Surveys were solicited via specialty-group listserv over a 3-mo interval. Respondents must have been practicing physicians with more than 20% clinical time spent in the inpatient setting. Within each specialty, consensus was established for any clinical score with greater than 70% of responses in a single category and a minimum of 10 responses. Logistic regression was performed to determine predictors of automation importance. RESULTS Seventy-nine divided by one hundred and forty-four (54.9%) surveys were completed and 72/144 (50%) surveys were completed by eligible respondents. Only the critical care and internal medicine specialties surpassed the 10-respondent threshold (14 respondents each). For internists, 2/110 (1.8%) of scores were “very important” and 73/110 (66.4%) were “nice to have”. For intensivists, no scores were “very important” and 26/76 (34.2%) were “nice to have”. Only the number of medical history (OR = 2.34; 95%CI: 1.26-4.67; P < 0.05) and vital sign (OR = 1.88; 95%CI: 1.03-3.68; P < 0.05) variables for clinical scores used by internists was predictive of desire for automation. CONCLUSION Few clinical scores were deemed “very important” for automated calculation. Future efforts towards score calculator automation should focus on technically feasible

  2. Clinical Decision Support Systems for the Practice of Evidence-based Medicine

    PubMed Central

    Sim, Ida; Gorman, Paul; Greenes, Robert A.; Haynes, R. Brian; Kaplan, Bonnie; Lehmann, Harold; Tang, Paul C.

    2001-01-01

    Background: The use of clinical decision support systems to facilitate the practice of evidence-based medicine promises to substantially improve health care quality. Objective: To describe, on the basis of the proceedings of the Evidence and Decision Support track at the 2000 AMIA Spring Symposium, the research and policy challenges for capturing research and practice-based evidence in machine-interpretable repositories, and to present recommendations for accelerating the development and adoption of clinical decision support systems for evidence-based medicine. Results: The recommendations fall into five broad areas—capture literature-based and practice-based evidence in machine-interpretable knowledge bases; develop maintainable technical and methodological foundations for computer-based decision support; evaluate the clinical effects and costs of clinical decision support systems and the ways clinical decision support systems affect and are affected by professional and organizational practices; identify and disseminate best practices for work flow–sensitive implementations of clinical decision support systems; and establish public policies that provide incentives for implementing clinical decision support systems to improve health care quality. Conclusions: Although the promise of clinical decision support system–facilitated evidence-based medicine is strong, substantial work remains to be done to realize the potential benefits. PMID:11687560

  3. 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.

  4. Digital video documentation as evidence of clinical skill acquisition.

    PubMed

    Edwards, Simon; Rajaratnam, V

    2009-01-01

    Video recordings have become requirements for the assessment and recording of the consulting skills module of the MRCGP examination and surgical skill modules for the post FRCS hand diploma examination. Previous research has shown that the knowledge and judgement skills needed by trainees to achieve operative competence can be reliably assessed using structured checklists. However evaluation of surgical competency should also include technical skills, which have been difficult to document adequately and transparently. There is now evidence demonstrating that surgeons can discriminate between the video recordings of a competent and non-competent trainee. Like those of previous researchers our findings indicate that intra-operative video monitoring enables an objective and permanent recordable assessment of the a trainees skill level whilst completing the checklist after a particular procedure. Video evidence can also be distributed widely to assessors outside the trainee's locale.

  5. Clinical data warehousing for evidence based decision making.

    PubMed

    Narra, Lekha; Sahama, Tony; Stapleton, Peta

    2015-01-01

    Large volumes of heterogeneous health data silos pose a big challenge when exploring for information to allow for evidence based decision making and ensuring quality outcomes. In this paper, we present a proof of concept for adopting data warehousing technology to aggregate and analyse disparate health data in order to understand the impact various lifestyle factors on obesity. We present a practical model for data warehousing with detailed explanation which can be adopted similarly for studying various other health issues.

  6. Excess 210Po in 2010 Eyjafjallajökull tephra (Iceland): Evidence for pre-eruptive gas accumulation

    NASA Astrophysics Data System (ADS)

    Sigmarsson, Olgeir; Condomines, Michel; Gauthier, Pierre-Jean

    2015-10-01

    Excess gas phase in magmas erupting explosively is well known worldwide. However, the origin of this gas phase, in excess of what can be dissolved in the erupting magma at depth, and the rate of gas accumulation is less well defined. The 2010 mildly explosive eruption at Eyjafjallajökull, Iceland, produced mingled tephra of benmoreitic and trachytic composition whereas alkali basalt was emitted during preceding flank eruption. Tephra of the first explosive phase are composed of three glass types, alkaline rhyolite, mixed benmoreite, and basalt, which suggests that the basaltic magma intruded a pre-existing rhyolitic magma chamber, and ultimately triggered the eruption. The mixed benmoreitic tephra (erupted on 15 and 17 April 2010) had large 210Po in excess of 210Pb [(210Po /210Pb) 0 = 1.88 ] at the time of eruption, and possibly a small 210Pb excess over its parent 226Ra. In contrast, the preceding flank eruption produced basalt with (210Po) 0 = 0, upon eruption, and the final trachyte had lost most of its 210Po during open-system degassing. The 210Po excess in the first erupted benmoreites is interpreted to result from 210Po degassing of basaltic magma and the accumulation of 210Po-enriched gas, either in the upper part of the basaltic intrusion, below the rhyolite-basalt interface, or in the pre-existing residual rhyolitic magma chamber. From a simple model of radon and polonium accumulation in the rhyolitic reservoir, the ratio of the mass of basalt magma degassing over the mass of magma accumulating the excess gas decreased from 20 to 15 over 2 days, implying zoned magma reservoir, with the uppermost and gas-richest part erupting first. The duration of pre-eruptive gas accumulation in this model is approximately one year. This corresponds closely to the initiation of a seismic swarm beneath Eyjafjallajökull, early June 2009, which was the first pre-eruptive signal detected. The coincidence between initiation of gas accumulation at relatively shallow depth and

  7. 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

  8. 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.

  9. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

    PubMed Central

    Aimo, Alberto; Borrelli, Chiara; Giannoni, Alberto; Pastormerlo, Luigi Emilio; Barison, Andrea; Mirizzi, Gianluca; Emdin, Michele; Passino, Claudio

    2015-01-01

    In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy. PMID:26516416

  10. Evaluation of Respiratory Muscle Strength in Mouth Breathers: Clinical Evidences

    PubMed Central

    Andrade da Cunha, Renata; Andrade da Cunha, Daniele; Assis, Roberta Borba; Bezerra, Luciana Ângelo; Justino da Silva, Hilton

    2013-01-01

    Introduction The child who chronically breathes through the mouth may develop a weakness of the respiratory muscles. Researchers and clinical are seeking for methods of instrumental evaluation to gather complementary data to clinical evaluations. With this in mind, it is important to evaluate breathing muscles in the child with Mouth Breathing. Objective To develop a review to investigate studies that used evaluation methods of respiratory muscle strength in mouth breathers. Data Synthesis  The authors were unanimous in relation to manovacuometry method as a way to evaluate respiratory pressures in Mouth Breathing children. Two of them performed with an analog manovacuometer and the other one, digital. The studies were not evaluated with regard to the method efficacy neither the used instruments. Conclusion There are few studies evaluating respiratory muscle strength in Mouth Breathing people through manovacuometry and the low methodological rigor of the analyzed studies hindered a reliable result to support or refuse the use of this technique. PMID:25992108

  11. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications

    PubMed Central

    Qureshi, Hammad; Sharafkhaneh, Amir

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD. PMID:25177479

  12. Paediatric lung recruitment: a review of the clinical evidence.

    PubMed

    Jauncey-Cooke, Jacqui; East, Chris E; Bogossian, Fiona

    2015-03-01

    Lung recruitment is used as an adjunct to lung protective ventilation strategies. Lung recruitment is a brief, deliberate elevation of transpulmonary pressures beyond what is achieved during tidal ventilation levels. The aim of lung recruitment is to maximise the number of alveoli participating in gas exchange particularly in distal and dependant regions of the lung. This may improve oxygenation and end expiratory levels. Restoration of end expiratory levels and stabilisation of the alveoli may reduce the incidence of ventilator induced lung injury (VILI). Various methods of lung recruitment have been studied in adult and experimental populations. This review aims to establish the evidence for lung recruitment in the pediatric population.

  13. Development of an evidence-based clinical practice guideline on linear growth measurement of children.

    PubMed

    Foote, Jan M; Brady, Linda H; Burke, Amber L; Cook, Jennifer S; Dutcher, Mary E; Gradoville, Kathleen M; Groos, Jennifer A; Kinkade, Kimberly M; Meeks, Reylon A; Mohr, Pamela J; Schultheis, Debra S; Walker, Brenda S; Phillips, Kirk T

    2011-08-01

    Growth is an important indicator of child health; however, measurements are frequently inaccurate and unreliable. This article reviews the literature on linear growth measurement error and describes methods used to develop and evaluate an evidence-based clinical practice guideline on the measurement of recumbent length and stature of infants, children, and adolescents. Systematic methods were used to identify evidence to answer clinical questions about growth measurement. A multidisciplinary team critically appraised and synthesized the evidence to develop clinical practice recommendations using an evidence-based practice rating scheme. The guideline was prospectively evaluated through internal and external reviews and a pilot study to ensure its validity and reliability. Adoption of the clinical practice guideline can improve the accuracy and reliability of growth measurement data.

  14. Advances in thyroid cancer treatment: latest evidence and clinical potential

    PubMed Central

    Alonso-Gordoa, T.; Díez, J.J.; Durán, M.

    2015-01-01

    Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting. PMID:25553081

  15. Diabetes and bone health: latest evidence and clinical implications

    PubMed Central

    Sundararaghavan, Vikram; Mazur, Matthew M.; Evans, Brad; Liu, Jiayong; Ebraheim, Nabil A.

    2017-01-01

    As the prevalence of diabetes is increasing worldwide, research on some of the lesser-known effects, including impaired bone health, are gaining a lot of attention. The two most common forms of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These two differ in their physiology, with T1DM stemming from an inability to produce insulin, and T2DM involving an insufficient response to the insulin that is produced. This review aims to highlight the most current information regarding diabetes as it relates to bone health. It looks at biochemical changes that characterize diabetic bone; notably increased adiposity, altered bone metabolism, and variations in bone mineral density (BMD). Then several hypotheses are analyzed, concerning how these changes may be detrimental to the highly orchestrated processes that are involved in bone formation and turnover, and ultimately result in the distinguishing features of diabetic bone. The review proceeds by explaining the effects of antidiabetes medications on bone health, then highlighting several ways that diabetes can play a part in other clinical treatment outcomes. With diabetes negatively affecting bone health and creating other clinical problems, and its treatment options potentiating these effects, physicians should consider the use of anti-osteoporotic drugs to supplement standard anti-diabetes medications in patients suffering with diabetic bone loss. PMID:28344668

  16. Seasonal fluctuations of deep megabenthos: Finding evidence of standing stock accumulation in a flux-rich continental slope

    NASA Astrophysics Data System (ADS)

    Tecchio, Samuele; Ramírez-Llodra, Eva; Aguzzi, Jacopo; Sanchez-Vidal, Anna; Flexas, M. Mar; Sardà, Francisco; Company, Joan B.

    2013-11-01

    Throughout the deep oceans, diversity in the benthos peaks at intermediate slope depths. In the western Mediterranean lower slope an accumulation of biomass, but not diversity, at depths of 1200-1350 m has been observed. However, the precise causes of this biomass peak are unknown. We examined the patterns of megafauna benthic biomass in the Catalan sea open slope, from 900 to 1750 m depth, expanding the results in the context of the whole continental margin. Sampling was carried out by combining an Otter-Trawl Maireta System (OTMS) and an Agassiz trawl, during four different seasons in 2008/2009. At the same time, current speed, temperature and salinity were obtained year-round by means of near-bottom deployed sensors (current meters and temperature-conductivity sensors). Total biomass followed an inverted U-shaped pattern, peaking at depths of 1050-1350 m. Range-related ecological forcings between shallower and deeper species may have caused this biomass accumulation at intermediate slope depths. We also report on the seasonal variations of biomass in the studied depth range, identifying a dynamic zone above 1000 m depth where populations of highly mobile species perform year-round migrations throughout the slope, and a more static region below 1000 m (i.e. the twilight zone end) with substantially less inter-annual variations. The arrival of new Western Mediterranean Deep Water from the deep basin to the lower slope in March-May may have driven the accumulation of biomass at 900 and 1050 m depth over the same period. In addition, an adjacent submarine canyon was sampled with the same procedures to characterize its benthic megafauna community. Analyses revealed higher diversity, but not biomass, inside the canyon than in the adjacent open slope, and a significantly different assemblage composition between the two habitats. These results strengthen the concept of submarine canyons as hotspots of biodiversity and underline the importance of their conservation as

  17. Conservation of arthropod midline netrin accumulation revealed with a cross-reactive antibody provides evidence for midline cell homology

    PubMed Central

    Simanton, Wendy; Clark, Stephanie; Clemons, Anthony; Jacowski, Caitlin; Farrell-VanZomeren, Adrienne; Beach, Paul; Browne, William E.; Duman-Scheel, Molly

    2009-01-01

    SUMMARY Although many similarities in arthropod CNS development exist, differences in axonogenesis and the formation of midline cells, which regulate axon growth, have been observed. For example, axon growth patterns in the ventral nerve cord of Artemia franciscana differ from that of Drosophila melanogaster. Despite such differences, conserved molecular marker expression at the midline of several arthropod species indicates that midline cells may be homologous in distantly related arthropods. However, data from additional species are needed to test this hypothesis. In this investigation, nerve cord formation and the putative homology of midline cells were examined in distantly related arthropods, including: long- and short-germ insects (D. melanogaster, Aedes aeygypti, and Tribolium castaneum), branchiopod crustaceans (A. franciscana and Triops longicauditus), and malacostracan crustaceans (Porcellio laevis and Parhyale hawaiensis). These comparative analyses were aided by a cross-reactive antibody generated against the Netrin (Net) protein, a midline cell marker and regulator of axonogenesis. The mechanism of nerve cord formation observed in Artemia is found in Triops, another branchiopod, but is not found in the other arthropods examined. Despite divergent mechanisms of midline cell formation and nerve cord development, Net accumulation is detected in a well-conserved subset of midline cells in branchiopod crustaceans, malacostracan crustaceans, and insects. Notably, the Net accumulation pattern is also conserved at the midline of the amphipod P. hawaiensis, which undergoes split germ-band development. Conserved Net accumulation patterns indicate that arthropod midline cells are homologous, and that Nets function to regulate commissure formation during CNS development of Tetraconata. PMID:19469853

  18. Respiratory clinical guidelines inform ward-based nurses’ clinical skills and knowledge required for evidence-based care

    PubMed Central

    Johnson, Alisha M.

    2016-01-01

    Respiratory clinical guidelines provide clinicians with evidence-based guidance for practice. Clinical guidelines also provide an opportunity to identify the knowledge and technical and non-technical skills required by respiratory ward-based registered nurses. The aim of this review was to use a systematic process to establish the core technical and non-technical skills and knowledge identified in evidence-based clinical guidelines that enable the care of hospitalised adult respiratory patients. 17 guidelines were identified in our systematic review. The quality assessment demonstrated variability in these guidelines. Common core knowledge and technical and non-technical skills were identified. These include pathophysiology, understanding of physiological measurements and monitoring, education, counselling, and ward and patient management. The knowledge and skills extracted from respiratory clinical guidelines may inform a curriculum for ward-based respiratory nursing to ensure optimal care of adult patients. PMID:28210299

  19. Respiratory clinical guidelines inform ward-based nurses' clinical skills and knowledge required for evidence-based care.

    PubMed

    Johnson, Alisha M; Smith, Sheree M S

    2016-09-01

    Respiratory clinical guidelines provide clinicians with evidence-based guidance for practice. Clinical guidelines also provide an opportunity to identify the knowledge and technical and non-technical skills required by respiratory ward-based registered nurses. The aim of this review was to use a systematic process to establish the core technical and non-technical skills and knowledge identified in evidence-based clinical guidelines that enable the care of hospitalised adult respiratory patients. 17 guidelines were identified in our systematic review. The quality assessment demonstrated variability in these guidelines. Common core knowledge and technical and non-technical skills were identified. These include pathophysiology, understanding of physiological measurements and monitoring, education, counselling, and ward and patient management. The knowledge and skills extracted from respiratory clinical guidelines may inform a curriculum for ward-based respiratory nursing to ensure optimal care of adult patients.

  20. Targeting dormant micrometastases: rationale, evidence to date and clinical implications.

    PubMed

    Hurst, Robert E; Bastian, Anja; Bailey-Downs, Lora; Ihnat, Michael A

    2016-03-01

    In spite of decades of research, cancer survival has increased only modestly. This is because most research is based on models of primary tumors. Slow recognition has begun that disseminated, dormant cancer cells (micrometastatic cells) that are generally resistant to chemotherapy are the culprits in recurrence, and until these are targeted effectively we can expect only slow progress in increasing overall survival from cancer. This paper reviews efforts to understand the mechanisms by which cancer cells can become dormant, and thereby identify potential targets and drugs either on the market or in clinical trials that purport to prevent metastasis. This review targets the most recent literature because several excellent reviews have covered the literature from more than two years ago. The paper also describes recent work in the authors' laboratories to develop a screening-based approach that does not require understanding of mechanisms of action or the molecular target. Success of this approach shows that targeting micrometastatic cells is definitely feasible.

  1. [When is enough evidence available?; interim analyses in clinical trials].

    PubMed

    van der Tweel, Ingeborg van; Roes, Kit C B

    2013-01-01

    There are ethical and economic reasons to design and conduct medical research as efficiently as possible. Clinical trials often take a long time because of the number of patients that must be included and the follow-up time in the study. Many data already become available during that time. By making interim analyses of these data it is possible to decide whether a final conclusion can be made. This may save time and may lead to a reduction in the number of patients. The statistical methodology of interim analyses is more complex than a fixed sample analysis and must be planned carefully in advance. The most important methods are sequential analysis and group sequential analysis. Both methods are aimed at a low risk of a false-positive conclusion. In this article we explain the application of these methods as well as considerations in the design of a study and interpretation of the results.

  2. Personalized therapy for urothelial cancer: review of the clinical evidence

    PubMed Central

    Guancial, Elizabeth A.; Chowdhury, Dipanjan; Rosenberg, Jonathan E.

    2012-01-01

    Despite a detailed understanding of the molecular aberrations driving the development of urothelial cancers, this knowledge has not translated into advances for the treatment of this disease. Urothelial cancers are chemosensitive, and platinum-based combination chemotherapy remains the standard of care for advanced disease, as well as neoadjuvant and adjuvant therapy for locally advanced disease. However, nearly half of patients who undergo resection of locally advanced urothelial cancer will relapse and eventually develop platinum-resistant disease. Clinical trials of targeted agents against angiogenesis and growth factors, as well as novel chemotheraputics, have generally been unsuccessful in urothelial cancers. Improvements in the theraputic arsenal for urothelial cancer depend upon identification of new targets and strategies to overcome platinum resistance. PMID:22754656

  3. Trimetazidine in Practice: Review of the Clinical and Experimental Evidence

    PubMed Central

    Dézsi, Csaba A.

    2016-01-01

    All of the following traditional agents for the management of stable angina pectoris include the symptomatic treatment with heart rate–lowering agents such as β-blockers or non-dihydropyridine Ca-channel blockers, or ivabradine—the first selective sinus node If channel inhibitor—vasodilatators and preventive use of angiotensin-converting enzyme inhibitors affect the parameters of circulation directly. Trimetazidine exerts its anti-ischemic action by modulating cardiac metabolism without altering the hemodynamic functions, therefore represents an excellent complementary potential to the conventional angina treatment. It has a beneficial effect on the inflammatory profile and endothelial function and shows diverse benefits by reducing the number and the intensity of angina attacks and improving the clinical signs and symptoms of myocardial ischemia given as monotherapy as well as combined with other antianginal agents. Patients undergoing coronary revascularization procedures or with comorbid left ventricular dysfunction and diabetes mellitus also benefit from the protective effects of trimetazidine. PMID:25756467

  4. Systematic evidence-based clinical practice guidelines are ushering in a new stage of standardized management of hepatocellular carcinoma in Japan.

    PubMed

    Song, Peipei; Tang, Wei; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2014-04-01

    Since the European Association for the Study of the Liver published their guidelines for hepatocellular carcinoma HCC (EASL Guideline) in 2001, there have been many explorations of "transferring best current evidence into clinical decision-making" around the worldwide. Comparative analysis on current 17 characteristic guidelines for HCC indicated that evidence-based clinical practice guidelines for HCC are urgently needed and appropriate constructing approach is the factor most significantly influencing their implementation. The construction of evidence-based clinical practice guidelines for HCC in Japan made a good example of this practice. In accordance with evidence-based medicine (EBM), the first version of the J-HCC Guidelines was published in 2005, then revised in 2009, and the third version has just been published on October 15, 2013 with the incorporation of new evidence, which marks the construction of evidence-based clinical practice guidelines for HCC step into a systematic process in Japan. In order to make a more clear description on how to construct evidence-based clinical practice guidelines for HCC in Japan, the three versions of the J-HCC Guidelines were comparatively analyzed in this paper. Focus on methodology used to develop the updated version, the decision tree of 2013 J-HCC Guideline and its features were also revealed. It is expected that J-HCC Guidelines could be useful not only for Japanese physicians and patients in decision making at every clinical step, but also to benefit users internationally with the accumulated evidence and its interpretation in the guidelines.

  5. Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.

    PubMed Central

    Rath, M; Pauling, L

    1990-01-01

    Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis. Images PMID:2147514

  6. Microcystin accumulation in cladocerans: first evidence of MC uptake from aqueous extracts of a natural bloom sample.

    PubMed

    Ferrão-Filho, Aloysio S; Herrera, Natalia A; Echeverri, Luis Fernando

    2014-09-01

    Bioaccumulation of microcystins (MC) in zooplankton has been shown in several studies, mainly in field samples. A few studies, however, have demonstrated MC bioaccumulation in laboratory experiments. Although ingestion of cell-bound MC is considered the main route of MC accumulation, another important source is the MC from the dissolved fraction (DMC). This study reports the accumulation of DMC from aqueous extracts of natural bloom samples in three cladoceran species: Moina micrura, Daphnia laevis and Daphnia similis. Animals were exposed for 96 h to aqueous extracts of lyophilized matter from two bloom samples from Colombian reservoirs in different concentrations (25-1000 mg DW L(-1)). Analysis by HPLC-MS detected MC-LR in these samples at concentrations of 434-538 μg g(-1). For the analysis of MC in animal tissues the samples were homogenized and sonicated in methanol:water (75%) and analyzed by ELISA. Results showed that the animals uptake of MC increased with increasing exposure concentrations of aqueous extracts, with M. micrura and D. laevis clones presenting the highest MC concentrations in their tissues (up to 1170-1260 μg g(-1)) while D. similis the lowest (184 μg g(-1)). This study shows, for the first time, that MC uptake from dissolved fraction by zooplankton is possible, not only from the ingestion of seston or cell-bound MC as previously demonstrated.

  7. MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation.

    PubMed

    Koya, K; Li, Y; Wang, H; Ukai, T; Tatsuta, N; Kawakami, M; Shishido; Chen, L B

    1996-02-01

    MKT-077 (formerly known as FJ-776) is a newly synthesized, highly water-soluble ( > 200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity in a variety of model systems. In culture, MKT-077 inhibits the growth of five human cancer cell lines (colon carcinoma CX-1, breast carcinoma MCF-7, pancreatic carcinoma (CRL 1420, bladder transitional cell carcinoma EJ, and melanoma LOX) but not monkey kidney CV-1, an indicator cell line for normal epithelial cells. In nude mice, MKT-077 inhibits the growth of s.c. implanted human renal carcinoma A498 and human prostate carcinoma DU145 and prolongs the survival of mice bearing i.p. implanted human melanoma LOX (tumor:control = 344%). Subcellular localization indicates that MKT-077 is taken up and retained by mitochondria, and flow cytometric analysis suggests that CX-1 cells take up MKT-077 to a much greater extent than CV-1 cells. Quantitation of MKT-077 uptake by ethanol extraction shows that CX-1 cells accumulate 65-fold more MKT-077 than do CV-1 cells. MKT-077 is the first delocalized lipophilic cation with a favorable pharmacological and toxicological profile in preclinical studies. MKT-077 is now being investigated in Phase I clinical trials.

  8. 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.

  9. Vitamin K Status and Vascular Calcification: Evidence from Observational and Clinical Studies12

    PubMed Central

    Shea, M. Kyla; Holden, Rachel M.

    2012-01-01

    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. PMID:22516723

  10. [Cancer treatment in elderly patients: evidence and clinical research].

    PubMed

    Repetto, Lazzaro; Luciani, Andrea

    2015-01-01

    In 2020 the percentage of patients with a diagnosis of cancer in people with more than 65 years will exceed 70% and 28% in ethnic minorities. The treatment of cancer in these populations is challenging for the oncologists due to socio-economic issues such as poverty, reduced access to the hospital care, level of education. The clinical pathway "diagnosis-treatment-cure", typical of the care of young patients has to be integrated in elderly patients with a more individualized treatment by means of comprehensive geriatric assessment (CGA). IADL (Instrumental Activities of Daily Living) have the best predictive role in oncological setting and their impairment significantly correlate with overall survival, chemotherapy toxicities and thirty days postoperative morbidities. The CGA is universally accepted as the most appropriate instrument to analitically evaluate the age related problems of elderly patients. The role of CGA is crucial to identify geriatric issues not easily diagnosed, to predict treatment toxicities, functional or cognitive decline, post operative complications and to estimate life expectancy. The CGA items are predictive of severe toxicity, however it is not clearly established which are the best performers and the best cut-offs points. Today CGA is integrated with physical performance tests (the most widely used is the "time up and go" test) and laboratory assay of Interleukin 6 and D-Dimer that correlate with mortality and physical decline. There are few prospective studies that evaluated the role of CGA in treatment choice. The first is a phase II study in solid tumors, the second is a haematological trial on non Hodgkin lymphoma. The largest trial is a 571 patients observational series that confirmed the role of CGA in decision making. The administration of CGA is time consuming and consequently some screening tools were developed. VES-13 is a 13 items tool that explores prevalently the functional status and the self reported health status. VES-13

  11. Diagnosis of Human Axillary Osmidrosis by Genotyping of the Human ABCC11 Gene: Clinical Practice and Basic Scientific Evidence

    PubMed Central

    Toyoda, Yu; Gomi, Tsuneaki; Nakagawa, Hiroshi; Nagakura, Makoto; Ishikawa, Toshihisa

    2016-01-01

    The importance of personalized medicine and healthcare is becoming increasingly recognized. Genetic polymorphisms associated with potential risks of various human genetic diseases as well as drug-induced adverse reactions have recently been well studied, and their underlying molecular mechanisms are being uncovered by functional genomics as well as genome-wide association studies. Knowledge of certain genetic polymorphisms is clinically important for our understanding of interindividual differences in drug response and/or disease risk. As such evidence accumulates, new clinical applications and practices are needed. In this context, the development of new technologies for simple, fast, accurate, and cost-effective genotyping is imperative. Here, we describe a simple isothermal genotyping method capable of detecting single nucleotide polymorphisms (SNPs) in the human ATP-binding cassette (ABC) transporter ABCC11 gene and its application to the clinical diagnosis of axillary osmidrosis. We have recently reported that axillary osmidrosis is linked with one SNP 538G>A in the ABCC11 gene. Our molecular biological and biochemical studies have revealed that this SNP greatly affects the protein expression level and the function of ABCC11. In this review, we highlight the clinical relevance and importance of this diagnostic strategy in axillary osmidrosis therapy. PMID:27057547

  12. Nivolumab in renal cell carcinoma: latest evidence and clinical potential

    PubMed Central

    Mazza, Camille; Escudier, Bernard; Albiges, Laurence

    2016-01-01

    Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10–20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses. The strategy of immune checkpoint blockade is to reduce inhibitory signaling and restore the patient’s natural tumor-specific T-cell-mediated immune responses. Nivolumab is the first PD-1 inhibitor to have gained approval for the treatment of patients with metastatic melanoma, squamous and nonsquamous non-small cell lung cancer (NSCLC), Hodgkin disease and recently RCC. In this review, we discuss results from studies of nivolumab in RCC, clinical experience with this agent, and its future development.

  13. Disinfection of Needleless Connector Hubs: Clinical Evidence Systematic Review

    PubMed Central

    Moureau, Nancy L.

    2015-01-01

    Background. Needleless connectors (NC) are used on virtually all intravascular devices, providing an easy access point for infusion connection. Colonization of NC is considered the cause of 50% of postinsertion catheter-related infections. Breaks in aseptic technique, from failure to disinfect, result in contamination and subsequent biofilm formation within NC and catheters increasing the potential for infection of central and peripheral catheters. Methods. This systematic review evaluated 140 studies and 34 abstracts on NC disinfection practices, the impact of hub contamination on infection, and measures of education and compliance. Results. The greatest risk for contamination of the catheter after insertion is the NC with 33–45% contaminated, and compliance with disinfection as low as 10%. The optimal technique or disinfection time has not been identified, although scrubbing with 70% alcohol for 5–60 seconds is recommended. Studies have reported statistically significant results in infection reduction when passive alcohol disinfection caps are used (48–86% reduction). Clinical Implications. It is critical for healthcare facilities and clinicians to take responsibility for compliance with basic principles of asepsis compliance, to involve frontline staff in strategies, to facilitate education that promotes understanding of the consequences of failure, and to comply with the standard of care for hub disinfection. PMID:26075093

  14. Possible Noninvasive Biomarker of Eosinophilic Esophagitis: Clinical and Experimental Evidence

    PubMed Central

    Venkateshaiah, Sathisha Upparahalli; Manohar, Murli; Verma, Alok K.; Blecker, Uwe; Mishra, Anil

    2016-01-01

    Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients. We show that CD274 expression on blood eosinophils and blood mRNA expression levels increase in the blood of EoE patients and decrease following treatment. These observations are consistent with the esophageal eosinophilia of before and after treatment in both examined patients. These two clinical and experimental analysis reports provide the possibility that the CD274 mRNA and CD274-expressing esinophil levels may be novel possible noninvasive biomarkers for EoE. PMID:27920662

  15. Lixisenatide in type 2 diabetes: latest evidence and clinical usefulness.

    PubMed

    Anderson, Sarah L; Trujillo, Jennifer M

    2016-01-01

    Type 2 diabetes (T2D) is a highly prevalent disorder that affects millions of people worldwide. The hallmark of T2D is hyperglycemia and, while many treatment modalities exist, achieving and maintaining glycemic control can be challenging. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an appealing treatment option as they improve glycemic control, reduce weight, and limit the risk of hypoglycemia. Lixisenatide is a once-daily GLP-1 RA that has been evaluated in the GetGoal clinical trial program and has demonstrated efficacy and tolerability across a spectrum of patients. The feature that most distinguishes lixisenatide from other GLP-1 RAs is its ability to substantially reduce postprandial glucose (PPG) for the meal immediately following injection. Because of its positive effects on PPG, lixisenatide is being considered as a replacement for prandial insulin, and a fixed dose combination product containing lixisenatide and basal insulin is in development. Lixisenatide is a promising new addition to the antidiabetic armamentarium, but due to the lack of real-world experience with the drug, its exact place in therapy is unknown.

  16. Possible Noninvasive Biomarker of Eosinophilic Esophagitis: Clinical and Experimental Evidence.

    PubMed

    Venkateshaiah, Sathisha Upparahalli; Manohar, Murli; Verma, Alok K; Blecker, Uwe; Mishra, Anil

    2016-01-01

    Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients. We show that CD274 expression on blood eosinophils and blood mRNA expression levels increase in the blood of EoE patients and decrease following treatment. These observations are consistent with the esophageal eosinophilia of before and after treatment in both examined patients. These two clinical and experimental analysis reports provide the possibility that the CD274 mRNA and CD274-expressing esinophil levels may be novel possible noninvasive biomarkers for EoE.

  17. Influence of Vegetation on Sediment Accumulation in Restored Tidal Saltmarshes: Field Evidence from the Blackwater Estuary, Essex, UK

    NASA Astrophysics Data System (ADS)

    Price, D.; French, J.; Burningham, H.

    2013-12-01

    Tidal saltmarshes in the UK, and especially in the estuaries of southeast England, have been subject to degradation and erosion over the last few decades, primarily caused by sea-level rise and coastal squeeze due to fixed coastal defences. This is of great concern to a range of coastal stakeholders due to the corresponding loss of functions and services associated with these systems. The coastal defence role that saltmarshes play is well established, and the importance of saltmarsh ecosystems as habitats for birds, fish, and other species is evidenced in the fact that a large proportion of saltmarsh in the southeast England is designated for its scientific and conservation significance. Sediment accumulation is critical for the maintenance of marsh elevation within the tidal frame and for delivery of the aforementioned functions and services. Although many studies have examined accumulation processes, key questions have yet to be fully tested through intensive field observations. One such question relates to the role of vegetation in mediating the retention of newly introduced sediment, as recent research has called into doubt the traditional view of halophytes significantly enhancing rates of sedimentation through wave dissipation. This study presents early results from a project designed to advance our understanding of the processes controlling sediment accumulation. The research focuses on the UK's first large-scale experimental managed flood defence realignment at Tollesbury, Blackwater estuary, Essex. The seawall protecting 21ha of reclaimed agricultural land was artificially breached in 1995 and saltmarsh has progressively developed as tidal exchange has introduced fine sediment into the site. Results from a 12 month monitoring campaign involving hierarchical two-week sediment trap deployments indicates that the role of vegetation in marsh development is less clear cut that previously thought. Gross sedimentation rates were generally higher in non

  18. Anticholinergic medication use and dementia: latest evidence and clinical implications

    PubMed Central

    Gray, Shelly L.; Hanlon, Joseph T.

    2016-01-01

    Use of medications with anticholinergic activity is widespread in older adults. Several studies have highlighted that anticholinergic use may be associated with an increased risk of dementia. The objective of this narrative review is to describe and evaluate studies of anticholinergic medication use and dementia and provide practical suggestions for avoiding use of these medications in older adults. A comprehensive review of the literature, citations from recent reviews and the author’s personal files was conducted. Four studies were found that evaluated anticholinergic use and dementia as the primary outcome. Three studies focused on overall anticholinergic medication use and reported a statistically significantly increased risk of Alzheimer’s disease or dementia. In one study, dementia risk was primarily found with higher cumulative doses; people using anticholinergic medications at the minimum effective dose recommended for older adults for at least 3 years were at highest risk. In contrast, a study conducted in nursing-home residents with depression did not find that paroxetine [a highly anticholinergic selective serotonin reuptake inhibitor antidepressant, (SSRI)] increased risk for dementia compared with other SSRIs (without anticholinergic activity). Further study is needed to understand the mechanism by which anticholinergic medications may increase risk. In conclusion, there is evidence from three observational studies suggesting that anticholinergic medications may increase dementia risk. Given this potential risk and the myriad of other well-known adverse effects (i.e. constipation, blurred vision, urinary retention, and delirium) associated with anticholinergic medications, it is prudent for prescribers and older adults to minimize use of these medications and consider alternatives when possible. PMID:27695623

  19. 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

  20. The biology and clinical evidence of microfracture in hip preservation surgery.

    PubMed

    Green, Chadwick John; Beck, Aswin; Wood, David; Zheng, Ming H

    2016-07-01

    The use of microfracture in hip arthroscopy is increasing dramatically. However, recent reports raise concerns not only about the lack of evidence to support the clinical use of microfracture, but also about the potential harm caused by violation of the subchondral bone plate. The biology and pathology of the microfracture technique were described based on observations in translational models and the clinical evidence for hip microfracture was reviewed systematically. The clinical outcomes in patients undergoing microfracture were the same as those not undergoing microfracture. However, the overall clinical evidence quality is poor in hips. This review identified only one study with Level III evidence, while most studies were Level IV. There were no randomized trials available for review. Repair tissue is primarily of fibrocartilaginous nature. Reconstitution of the subchondral bone is often incomplete and associated with poor quality repair tissue and faster degeneration. Subchondral bone cyst formation is associated with microfracture, likely secondary to subchondral bone plate disruption and a combination of pressurized synovial fluid and inflammatory mediators moving from the joint into the bone. There is a lack of clinical efficacy evidence for patients undergoing microfracture. There is evidence of bone cyst formation following microfracture in animal studies, which may accelerate joint degeneration. Bone cyst formation following microfracture has not been studied adequately in humans.

  1. PCB and OCP accumulation and evidence of hepatic alteration in the Atlantic bluefin tuna, T. thynnus, from the Mediterranean Sea.

    PubMed

    Maisano, Maria; Cappello, Tiziana; Oliva, Sabrina; Natalotto, Antonino; Giannetto, Alessia; Parrino, Vincenzo; Battaglia, Pietro; Romeo, Teresa; Salvo, Andrea; Spanò, Nunziacarla; Mauceri, Angela

    2016-10-01

    Persistent organic pollutants (POPs) are known to act as "obesogens", being fat-soluble and affecting lipid metabolism. The Atlantic bluefin tuna, Thunnus thynnus, are top pelagic predators prone to bioaccumulate and biomagnify environmental contaminants. This study aimed at evaluating POPs-induced ectopic lipid accumulation in liver of adult tuna from the Mediterranean Sea. PCBs and organochlorine pesticides were measured in tuna liver, and marked morphological changes observed, namely poorly compacted tissues, intense vacuolization, erythrocyte infiltration and presence of melanomacrophages. The expression of perilipin, a lipid-droplet marker, positively correlated with the gene expression of PPARγ, a master regulator of adipogenesis, and its heterodimeric partner, RXRα. Changes in metabolites involved in fatty acid biosynthesis and ketogenesis were also observed. Although male bluefin tuna appeared to be more sensitive than females to the adverse effects of environmental obesogens, the alterations observed in tuna liver of both sexes suggest a potential onset of hepatic steatosis.

  2. Evidence for a photoprotective function of low-temperature-induced anthocyanin accumulation in apple and pear peel.

    PubMed

    Steyn, Willem J; Wand, Stephanie J E; Jacobs, Gerard; Rosecrance, Richard C; Roberts, Stephanie C

    2009-08-01

    The light requirement and low-temperature stimulation of anthocyanin synthesis in peel of apple (Malus domestica) and pears (Pyrus communis) and the presence of anthocyanins in immature fruits are not congruent with a visual function in dispersal. We hypothesized that anthocyanins afford photoprotection to peel during low-temperature-induced light stress and that the protection is not a fortuitous side-effect of light absorption by anthocyanin. The extent of photoinhibition at harvest and after light stress treatment in pear cultivars differing in redness decreased with increasing red color on the sun-exposed sides of fruits. Green-shaded sides of the pears showed comparable levels of photoinhibition indicating that pears did not differ in their inherent photosensitivity. Apple and pear peel show considerable short-term fluctuation in redness in response to temperature, with red color increasing rapidly in response to low temperature and just as quickly fading in response to high temperature. Briefly, shading pears and apples during cold conditions for 2 days reduced the accumulation of anthocyanin and increased the photosensitivity of peel. Subsequent shading during warm conditions did not affect the accumulation of anthocyanin or the photosensitivity of peel indicating that the response at low temperature was not due to shade adaptation. The assessment of photosystem II (PSII) efficiency and quenching of chlorophyll fluorescence between 16 and 40 degrees C indicated that 'Forelle' pear peel was particularly sensitive to photostress at low temperature. The photosynthetic system in mature 'Forelle' leaves was comparatively much less sensitive to light stress at low temperature. Results support the view that anthocyanins are adaptable light screens deployed to modulate light absorption in sensitive tissues such as fruit peel in response to environmental triggers such as cold front snaps.

  3. Evidence-based clinical use of insulin premixtures

    PubMed Central

    2013-01-01

    Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient’s clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil. PMID:24011173

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

    PubMed Central

    Heitz, Richard P.; Schall, Jeffrey D.

    2013-01-01

    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. PMID:24018731

  5. Evaluation tool for clinical nursing textbooks: bridging content analysis with evidence.

    PubMed

    Cassata, Linda C; Cox, Tina M

    2009-06-01

    One of the challenges nurse educators face is choosing a textbook that ensures congruency within the discipline of nursing, national and global health priorities, and the mission of the university. This article discusses the development of a tool that evaluates course content concurrently with evidence. The need to critically link content analysis and evidence within clinical nursing textbooks is deemed important given the discipline's imperative to prepare nurses to use the best evidence available for practice. The history and concept of evidence-based nursing practice is explored to develop an operational definition for the tool, which was designed to guide a realistic and expeditious process for this important faculty responsibility.

  6. Transient accumulation of Mg-protoporphyrin IX regulates expression of PhANGs - New evidence for the signaling role of tetrapyrroles in mature Arabidopsis plants.

    PubMed

    Zhang, Zhong-Wei; Yuan, Shu; Feng, Hong; Xu, Fei; Cheng, Jian; Shang, Jing; Zhang, Da-Wei; Lin, Hong-Hui

    2011-05-01

    Genetic and physiological studies have revealed evidence for multiple signaling pathways by which the plastid exerts retrograde control over photosynthesis associated nuclear genes (PhANGs). It has been proposed that the tetrapyrrole pathway intermediate Mg-protoporphyrin IX (Mg-proto IX) acts as the signaling molecule in the pathways and accumulates in the chloroplasts and cytosol of the cell after treatment with the herbicide Norflurazon (NF). However, the role of Mg-Proto IX in plastid signaling has been challenged by two recent reports. In this paper, new evidence is presented supporting Mg-Proto IX as a plastid-signaling molecule in mature Arabidopsis seedlings. Fluorescence HPLC and confocal microscope observation verified that a short-term (<96h) NF treatment resulted in a large accumulation of Mg-Proto IX accompanying with Lhcb repression, whereas the long-term NF treatments caused marked changes of tetrapyrrole pools, while Lhcb expression was continuously repressed. These results may explain the discrepancies among different reports. Reactive oxygen species (ROS) eliminator treatments only partly reversed the NF-induced repression of Lhcb. Therefore, the NF generates both ROS signals and Mg-Proto IX signals. Furthermore, our data suggested that plastid signal transduction through plastid GUN1 protein is independent of tetrapyrrole export from the plastid.

  7. Accumulating Evidence for the Association and Shared Pathogenic Mechanisms between Psoriasis and Cardiovascular–Related Co-morbidities

    PubMed Central

    Shlyankevich, Julia; Mehta, Nehal N.; Krueger, James G.; Strober, Bruce; Gudjonsson, Johann E.; Qureshi, Abrar A.; Tebbey, Paul W.; Kimball, Alexandra Boer

    2014-01-01

    The International Psoriasis Council (IPC), a global non-profit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, MA. By assembling a panel of global dermatology, immunology and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. IPC has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity. PMID:25149424

  8. Using problem-based learning in the clinical setting to improve nursing students' critical thinking: an evidence review.

    PubMed

    Oja, Kenneth J

    2011-03-01

    In preparation for the progressive nature of today's acute care hospital environments and the requirements for safe and effective patient care, it is essential that nursing students learn how to think critically. Problem-based learning is a method of education designed to encourage critical thinking. This article examines the evidence regarding the use of problem-based learning to improve critical thinking. A review of published literature was conducted using the CINAHL, ERIC, PsychInfo, and PubMed databases with the keywords nursing, problem-based learning, and critical thinking. Although the evidence is still accumulating, the studies reviewed indicate a positive relationship between problem-based learning and improved critical thinking in nursing students. There is a need for more rigorous research on the use of problem-based learning to examine the effects on critical thinking. Until this occurs, nursing instructors must rely on the extant evidence to guide their practice or continue to use the traditional model of clinical nursing education.

  9. An Extraordinary Accumulation of (-)-Pinoresinol in Cell-Free Extracts of Forsythia intermedia: Evidence for Enantiospecific Reduction of (+)-Pinoresinol

    NASA Technical Reports Server (NTRS)

    Katayama, Takeshi; Davin, Laurence B.; Lewis, Norman G.

    1992-01-01

    Stereoselective and enantiospecific transformation mechanisms in lignan biogenesis are only now yielding to scientific inquiry: it has been shown that soluble cell-free preparations from Forsythia intermedia catalysis the formation of the enantiomerically pure lignan, (-)-secoisolariciresinol, when incubated with coniferyl alcohol in the presence of NAD(P)H and H2O2. Surprisingly, (-)-pinoresinol also accumulates in this soluble cell-free assay mixture in greater than 96% enantiomeric excess, even though it is not the naturally occurring antipode present in Forsythia sp. But these soluble cell-free preparations do not engender stereoselective coupling; instead, racemic pinoresinols are first formed, catalysed by an H2O2-dependent peroxidase reaction. An enantiospecific NAD(P)H reductase then converts (+)- pinoresinol, and not the (-)-antipode, into (-)-secoisolariciresinol. Stereoselective syntheis of(+)-pinoresinol from E-coniferyl alcohol is, however, catalysed by an insoluble enzyme preparation in F. suspensa, obtained following removal of readily soluble and ionically bound enzymes; no exogenously supplied cofactors were required other than oxygen, although the reaction was stimulated by NAD-malate addition. Thus, the overall biochemical pathway to enantiomerically pure (-)-secoisolariciresinol has been delineated.

  10. Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement.

    PubMed

    Hurria, Arti; Levit, Laura A; Dale, William; Mohile, Supriya G; Muss, Hyman B; Fehrenbacher, Louis; Magnuson, Allison; Lichtman, Stuart M; Bruinooge, Suanna S; Soto-Perez-de-Celis, Enrique; Tew, William P; Postow, Michael A; Cohen, Harvey J

    2015-11-10

    The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, because older adults are underrepresented in clinical trials, and trials designed specifically for older adults are rare. The result is that clinicians have less evidence on how to treat older adults, who represent the majority of patients with cancer. Clinicians and patients are forced to extrapolate from trials conducted in younger, healthier populations when developing treatment plans. This has created a dearth of knowledge regarding the risk of toxicity in the average older patient and about key end points of importance to older adults. ASCO makes five recommendations to improve evidence generation in this population: (1) Use clinical trials to improve the evidence base for treating older adults with cancer, (2) leverage research designs and infrastructure for generating evidence on older adults with cancer, (3) increase US Food and Drug Administration authority to incentivize and require research involving older adults with cancer, (4) increase clinicians' recruitment of older adults with cancer to clinical trials, and (5) use journal policies to improve researchers' reporting on the age distribution and health risk profiles of research participants.

  11. Properties of Modern Dust Accumulating in the Uinta Mountains, Utah, USA, and Soil Evidence of Long-Term Dust Deposition

    NASA Astrophysics Data System (ADS)

    Munroe, J. S.

    2013-12-01

    Modern eolian sediment was collected at four locations in the alpine zone of the Uinta Mountains (Utah, USA) between July 2011 and July 2012. Collectors were a passive design based on the classic marble dust trap, but modified for use in this high-precipitation environment. On average the collectors accumulated 1.5 gm of dust, corresponding to an annual flux of 4.4 g/m2. This result is similar to values measured from snowpack samples in the Wind River (Wyoming) and San Juan (Colorado) Mountains. Dust flux was 3 to 5x higher during the winter compared with summer at the two sites featuring continuous vegetation, but was consistent between the seasons at the two collectors surrounded by a greater area of exposed soil. XRD analysis reveals that dust samples are dominated by quartz, potassium feldspar, plagioclase, and illite. Some samples contain amphibole and chlorite. In contrast, samples of fine sediment collected from the surface of modern snowbanks are dominated by clay with no feldspar or quartz, suggesting that these minerals are derived from the surrounding soil surface, which is snow-covered in the winter. ICP-MS analysis reveals that the geochemistry of the coarse (>63-μm) fraction of the dust resembles that of the underlying bedrock, confirming a local origin for this sediment. In contrast, the fine (<63-μm) fraction of the dust closely matches the fine fraction of the soil A horizon, supporting an eolian origin for the ubiquitous layer of fines that mantles soil profiles throughout the Uinta Mountains. Grain size analysis with laser scattering reveals that modern dust is very well-sorted, with a median size of 8 μm (7.0 Φ). Using the annual dust flux and mean grain size, and taking into account the measured bulk density (0.95 gm/cm3), organic matter content (20%), and silt content (32%) of this loess cap, the extrapolated loess accretion rate is ~18 cm per 10,000 years. Given that prior studies (Bockheim et al., 2000 Catena; Munroe, 2007, Arctic

  12. Practice nurse use of evidence in clinical practice: a descriptive survey.

    PubMed

    Prior, Patsy; Wilkinson, Jill; Neville, Stephen

    2010-08-01

    The role of practice nurses is a specific feature of the modernisation agenda of the New Zealand health service. Increasing importance is being placed on service improvement through effective decision making and enhanced clinical performance. To contribute to the development of primary health care it is crucial that nurses have the skills to appropriately implement research based and other evidence in practice. This study involved 55 West Auckland practice nurses working in the general practice setting. The aim of the study was to describe nurses' perceptions of their use of evidence-based practice, attitudes toward evidence-based practice and perceptions of their knowledge/skills associated with evidence-based practice. An additional aim was to determine the effect of educational preparation on practice, attitudes and knowledge/skills toward evidence-based practice. A descriptive survey design was selected for this study. The results demonstrated that nurses' attitudes toward evidence-based practice, knowledge and skills relevant to the implementation of evidence-based practice and the educational preparation of the nurses were important factors influencing the effective utilisation and application of research results in practice. Educational interventions are identified as an integral aspect of implementing evidence-based practice and enhancing practice nurses' knowledge and skill relevant to the use of evidence in practice. Further research is needed to assess the contextual factors which can inhibit or promote achievement of evidence-based practice by practice nurses.

  13. Clinical expert facilitators of evidence-based practice: a community hospital program.

    PubMed

    Rutledge, Dana N; Skelton, Katie

    2011-01-01

    A 1-year program for select clinical nurse experts led to increased comfort in using evidence-based practice strategies. Nurses identified specific barriers and facilitators for evidence-based practice efforts, accomplished individual goals, and saw changes in their practice roles. Results from the program and its evaluation are that staff can benefit from such an effort (4-day course with specific follow-up activities).

  14. OrthoEvidence™: A Clinical Resource for Evidence-Based Orthopedics

    PubMed Central

    Sprague, Sheila; Smith, Chris; Bhandari, Mohit

    2015-01-01

    The prevalence of musculoskeletal issues in clinical practice, and the limited focus placed upon musculoskeletal conditions by current electronic summary resources, highlights the need for a resource that provides access to simple and concise summaries of top-quality orthopedic literature for orthopedic surgeons and allied healthcare professionals. OrthoEvidence™ is an online clinical resource that addresses the paucity of adequate evidence-based summary tools in the field of orthopedic surgery. OrthoEvidence™ uses a rigorous, transparent, and unique process to review, evaluate, and summarize high quality research studies and their implications for orthopedic clinical practice. Randomized controlled trials and meta-analyses are identified and reviewed by an expert medical writing team, who prepare Advanced Clinical Evidence (ACETM) reports: one or two detailed pages including critical appraisals and synopses of key research. These timely and targeted reports provide a clear understanding about the quality of evidence associated with each summarized study, and can be organized by users to identify trending information. OrthoEvidence™ allows members to use their time efficiently and to stay current by having access to a breadth of timely, high-quality research output. OrthoEvidence™ is easily accessible through the internet and is available at the point-of-care, which allows treating orthopedic surgeons and allied health professionals to easily practice the principles of evidence-based medicine within their clinical practices.. PMID:26330990

  15. Debris-covered piedmont glaciers along the northwest flank of the Olympus Mons scarp: Evidence for low-latitude ice accumulation during the Late Amazonian of Mars

    NASA Astrophysics Data System (ADS)

    Milkovich, Sarah M.; Head, James W.; Marchant, David R.

    2006-04-01

    We use Viking and new MGS and Odyssey data to characterize the lobate deposits superimposed on aureole deposits along the west and northwest flanks of Olympus Mons, Mars. These features have previously been interpreted variously as landslide, pyroclastic, lava flow or glacial features on the basis of Viking images. The advent of multiple high-resolution image and topography data sets from recent spacecraft missions allow us to revisit these features and assess their origins. On the basis of these new data, we interpret these features as glacial deposits and the remnants of cold-based debris-covered glaciers that underwent multiple episodes of advance and retreat, occasionally interacting with extrusive volcanism from higher on the slopes of Olympus Mons. We subdivide the deposits into fifteen distinctive lobes. Typical lobes begin at a theater-like alcove in the escarpment at the base of Olympus Mons, interpreted to be former ice-accumulation zones, and extend outward as a tongue-shaped or fan-shaped deposit. The surface of a typical lobe contains (moving outward from the basal escarpment): a chaotic facies of disorganized hillocks, interpreted as sublimation till in the accumulation zone; arcuate-ridged facies characterized by regular, subparallel ridges and interpreted as the ridges of surface debris formed by the flow of underlying ice; and marginal ridges interpreted as local terminal moraines. Several lobes also contain a hummocky facies toward their margins that is interpreted as a distinctive type of sublimation till shaped by structural dislocations and preferential loss of ice. Blocky units are found extending from the escarpment onto several lobes; these units are interpreted as evidence of lava-ice interaction and imply that ice was present at a time of eruptive volcanic activity higher on the slopes of Olympus Mons. Other than minor channel-like features in association with lava-ice interactions, we find no evidence for the flow of liquid water in

  16. Evidence of liquid phase during laser-induced periodic surface structures formation induced by accumulative ultraviolet picosecond laser beam

    SciTech Connect

    Huynh, T. T. D.; Petit, A.; Semmar, N.

    2015-11-09

    Laser-induced periodic surface structures (LIPSS) were formed on Cu/Si or Cu/glass thin films using Nd:YAG laser beam (40 ps, 10 Hz, and 30 mJ/cm{sup 2}). The study of ablation threshold is always achieved over melting when the variation of the number of pulses increases from 1 to 1000. But the incubation effect is leading to reduce the threshold of melting as increasing the number of laser pulse. Also, real time reflectivity signals exhibit typical behavior to stress the formation of a liquid phase during the laser-processing regime and helps to determine the threshold of soft ablation. Atomic Force Microscopy (AFM) analyses have shown the topology of the micro-crater containing regular spikes with different height. Transmission Electron Microscopy (TEM) allows finally to show three distinguished zones in the close region of isolated protrusions. The central zone is a typical crystallized area of few nanometers surrounded by a mixed poly-crystalline and amorphous area. Finally, in the region far from the protrusion zone, Cu film shows an amorphous structure. The real time reflectivity, AFM, and HR-TEM analyses evidence the formation of a liquid phase during the LIPSS formation in the picosecond regime.

  17. Synchrotron FTIR shows evidence of DNA damage and lipid accumulation in prostate adenocarcinoma PC-3 cells following proton irradiation

    NASA Astrophysics Data System (ADS)

    Lipiec, Ewelina; Bambery, Keith R.; Heraud, Phil; Hirschmugl, Carol; Lekki, Janusz; Kwiatek, Wojciech M.; Tobin, Mark J.; Vogel, Christian; Whelan, Donna; Wood, Bayden R.

    2014-09-01

    Synchrotron Radiation Fourier Transform Infrared (SR-FTIR) spectra of single human prostate adenocarcinoma PC-3 cells, irradiated with a defined number of 2 MeV protons generated by a proton microbeam along with non-irradiated control cells, were analysed using multivariate methods. A number of different Principal Component Analysis (PCA) models were tested and the spectral ranges associated with nucleic acids, proteins and lipids were analysed separately. The results show a dose dependent shift of the Osbnd Psbnd O asymmetric stretching mode from 1234 cm-1 to 1237 cm-1, consistent with local disorder in the B-DNA conformation along with a change in intensity of the Osbnd Psbnd O symmetric stretching band at 1083 cm-1 indicative of chromatin fragmentation - the natural consequence of a high number of DNA Double Strand Breaks (DSBs). 2D mapping of characteristic functional groups at the diffraction limit shows evidence of lipid deposition and chromatin condensation in cells exposed to protons indicative of cell apoptosis following irradiation. These studies lay the foundation for understanding the macromolecular changes that occur to cells in response to radiation therapy, which has important implications in the treatment of tumours.

  18. Comparative clinical trials and the changing marketplace for oral care: innovation, evidence and implications.

    PubMed

    Gerlach, Robert W; Biesbrock, Aaron R

    2002-09-01

    The development of a trayless bleaching system (Crest Whitestrips) and a novel battery-powered toothbrush (Crest SpinBrush) has fueled growth in the bleaching and power toothbrush markets. Beyond offering convenient, low-cost options for patients, the effectiveness of each product is supported by a robust clinical program. New comparative research involving these products expands evidence on the clinical meaningfulness of the benefits of this whitening system and powered toothbrush for patient care.

  19. 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

  20. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    PubMed

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  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. Evaluating research for clinical significance: using critically appraised topics to enhance evidence-based neuropsychology.

    PubMed

    Bowden, Stephen C; Harrison, Elise J; Loring, David W

    2014-01-01

    Meehl's (1973, Psychodiagnosis: Selected papers. Minneapolis: University of Minnesota Press) distinction between statistical and clinical significance holds special relevance for evidence-based neuropsychological practice. Meehl argued that despite attaining statistical significance, many published findings have limited practical value since they do not inform clinical care. In the context of an ever expanding clinical research literature, accessible methods to evaluate clinical impact are needed. The method of Critically Appraised Topics (Straus, Richardson, Glasziou, & Haynes, 2011, Evidence-based medicine: How to practice and teach EBM (4th ed.). Edinburgh: Elsevier Churchill-Livingstone) was developed to provide clinicians with a "toolkit" to facilitate implementation of evidence-based practice. We illustrate the Critically Appraised Topics method using a dementia screening example. We argue that the skills practiced through critical appraisal provide clinicians with methods to: (1) evaluate the clinical relevance of new or unfamiliar research findings with a focus on patient benefit, (2) help focus of research quality, and (3) incorporate evaluation of clinical impact into educational and professional development activities.

  3. Evidence of self organization in great Sumatra earthquake recurrence times: Implications for coupling of tidal forcing and tectonic stress accumulation

    NASA Astrophysics Data System (ADS)

    Tiwari, R. K.; Puli, K.

    2012-12-01

    We analyzed inter- event time series of earthquake activities (M≥ 5) of Sumatra region spanning over 1973 to 2009 using techniques of nonlinear dynamics. The earthquake data were taken from the USGS catalogue centered on latitude 3.240N and longitude 95.825E. As a first step, in our analyses we computed the rank order statistics which revealed mixed response of earthquake dynamics indicating distinct breaks in slope of the rank order. This suggests that earthquake dynamics in this region is partly unstable and partly "self-organized" with a random tail. Comparison of return maps of the earthquakes inter- event time series with those representing random, stochastic and chaotic processes shows a quasi-deterministic behavior of earthquake genesis in the region. We further assessed the dimensionality of earthquake-generating mechanisms using a nonlinear predictor technique on two dimensional phase portrait constructed by recurrence time series. The nonlinear forecasting analysis suggests that the earthquake processes in the Sumatra region evolve on a non-random low-dimensional chaotic plane. Further, "K2" Entropy revealed a coherent structure indicating the deterministic dynamical pattern. This analysis is consistent with "self-organized" processes which could be explained invoking earth's internal dynamics, where, impulsively derived interdependencies cascades through the stress generated by tectonic plate movement. Our results, however, do not preclude the role of coupling of the above self-organized system with tidal forcing. Evidence for such a coupling in this region exists as 'triggering force". Keywords: Sumatra Earthquakes, Quasi-deterministic, Stochastic, Chaotic, Self-organized, K2 entropy, Phase portrait.

  4. Evidence of Cholesterol Accumulated in High Curvature Regions: Implication ot the Curvature Elastic Energy for Lipid Mixtures

    SciTech Connect

    Wang,W.; Yang, L.; Huang, H.

    2007-01-01

    Recent experiments suggested that cholesterol and other lipid components of high negative spontaneous curvature facilitate membrane fusion. This is taken as evidence supporting the stalk-pore model of membrane fusion in which the lipid bilayers go through intermediate structures of high curvature. How do the high-curvature lipid components lower the free energy of the curved structure? Do the high-curvature lipid components modify the average spontaneous curvature of the relevant monolayer, thereby facilitate its bending, or do the lipid components redistribute in the curved structure so as to lower the free energy? This question is fundamental to the curvature elastic energy for lipid mixtures. Here we investigate the lipid distribution in a monolayer of a binary lipid mixture before and after bending, or more precisely in the lamellar, hexagonal, and distorted hexagonal phases. The lipid mixture is composed of 2:1 ratio of brominated di18:0PC and cholesterol. Using a newly developed procedure for the multiwavelength anomalous diffraction method, we are able to isolate the bromine distribution and reconstruct the electron density distribution of the lipid mixture in the three phases. We found that the lipid distribution is homogenous and uniform in the lamellar and hexagonal phases. But in the distorted hexagonal phase, the lipid monolayer has nonuniform curvature, and cholesterol almost entirely concentrates in the high curvature region. This finding demonstrates that the association energies between lipid molecules vary with the curvature of membrane. Thus, lipid components in a mixture may redistribute under conditions of nonuniform curvature, such as in the stalk structure. In such cases, the spontaneous curvature depends on the local lipid composition and the free energy minimum is determined by lipid distribution as well as curvature.

  5. Analysis of the accumulation of Pea enation mosaic virus genomes in seed tissues and lack of evidence for seed transmission in pea (Pisum sativum).

    PubMed

    Timmerman-Vaughan, Gail; Larsen, Richard; Murray, Sarah; McPhee, Kevin; Coyne, Clarice

    2009-11-01

    Pea enation mosaic virus (PEMV) is an important virus disease of pea. International movement of commercial pea cultivars and germplasm can be problematic due to uncertainty about seed transmission of the viruses responsible for the disease. Whether PEMV is seedborne was assessed by collecting developing seed from infected plants and determining the relative concentrations of the PEMV-1 and PEMV-2 viral genomes using quantitative real-time reverse-transcription polymerase chain reaction. The relative accumulation of PEMV-1 and PEMV-2 was approximately 1,240 and 13,000 times higher, respectively, in leaf than in embryo tissues. Accumulation of PEMV-1 and PEMV-2 RNA was also significantly higher in pod walls and seed coats than in cotyledons or embryo axes. No evidence was obtained for seed transmission of PEMV in pea. Although PEMV-1 and PEMV-2 genomic RNAs were found in developing seed, no PEMV symptoms were observed in the field on more than 50,000 plants from seed derived from PEMV-infected source plants. These data demonstrate that PEMV is seedborne in pea but do not support a previous report that PEMV is seed transmitted. Absence of seed transmission may result from the low abundance of PEMV viral genomes in embryo tissue.

  6. 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.

  7. 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

    2016-05-24

    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.

  8. Evidence-Based Youth Psychotherapies Versus Usual Clinical Care: A Meta-Analysis of Direct Comparisons

    ERIC Educational Resources Information Center

    Weisz, John R.; Jensen-Doss, Amanda; Hawley, Kristin M.

    2006-01-01

    In the debate over evidence-based treatments (EBTs) for youth, one question is central: Do EBTs produce better outcomes than the usual interventions employed in clinical care? The authors addressed this question through a meta-analysis of 32 randomized trials that directly compared EBTs with usual care. EBTs outperformed usual care. Effects fell…

  9. 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…

  10. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND...

  11. 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).…

  12. 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…

  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. Acute pain management in morbid obesity - an evidence based clinical update.

    PubMed

    Budiansky, Adele Sandra; Margarson, Michael P; Eipe, Naveen

    2017-03-01

    Increasing numbers of patients with morbid obesity are presenting for surgery and their acute pain management requires an evidence-based clinical update. The objective of this study was to complete a literature review for acute pain management in morbid obesity and provide an evidence-based clinical update with recommendations. Using standardized search terms, in March 2015, we completed a literature search to determine evidence for different acute pain pharmacological modalities in morbid obesity. For each modality the highest level of evidence was ascertained and recommendations for each pharmacological modality are presented. Though overall evidence is limited to few well conducted clinical trials, mostly related to weight loss surgery, multimodal analgesia with step-wise, severity-based, opioid-sparing approach appears to improve acute pain management in morbid obesity. The perioperative use of non-opioid adjuvants appears to offer further improvements in patient safety and outcomes. Further research into standardization of pain assessments and implementation of acute pain management protocols is required.

  15. 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.

  16. Why many clinical psychologists are resistant to evidence-based practice: root causes and constructive remedies.

    PubMed

    Lilienfeld, Scott O; Ritschel, Lorie A; Lynn, Steven Jay; Cautin, Robin L; Latzman, Robert D

    2013-11-01

    Psychotherapists are taught that when a client expresses resistance repeatedly, they must understand and address its underlying sources. Yet proponents of evidence-based practice (EBP) have routinely ignored the root causes of many clinical psychologists' reservations concerning the use of scientific evidence to inform clinical practice. As a consequence, much of the resistance to EBP persists, potentially widening the already large scientist-practitioner gap. Following a review of survey data on psychologists' attitudes toward EBP, we examine six sources underpinning resistance toward EBP in clinical psychology and allied domains: (a) naïve realism, which can lead clinicians to conclude erroneously that client change is due to an intervention itself rather than to a host of competing explanations; (b) deep-seated misconceptions regarding human nature (e.g., mistaken beliefs regarding the causal primacy of early experiences) that can hinder the adoption of evidence-based treatments; (c) statistical misunderstandings regarding the application of group probabilities to individuals; (d) erroneous apportioning of the burden of proof on skeptics rather than proponents of untested therapies; (e) widespread mischaracterizations of what EBP entails; and (f) pragmatic, educational, and attitudinal obstacles, such as the discomfort of many practitioners with evaluating the increasingly technical psychotherapy outcome literature. We advance educational proposals for articulating the importance of EBP to the forthcoming generation of clinical practitioners and researchers, and constructive remedies for addressing clinical psychologists' objections to EBP.

  17. 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.

  18. "Not Just Right Experiences" are specific to obsessive-compulsive disorder: further evidence from Italian clinical samples.

    PubMed

    Sica, Claudio; Bottesi, Gioia; Orsucci, Antonella; Pieraccioli, Caterina; Sighinolfi, Cecilia; Ghisi, Marta

    2015-04-01

    Not Just Right Experiences (NJREs) are considered to be a perceptually tinged phenomenon mainly related to obsessive-compulsive disorder (OCD). The evidence of an association between NJREs and OCD or OC symptoms have been accumulating in the last few years, whereas there is a paucity of studies about the role of this construct in other clinical conditions considered part of the "OCD spectrum". In the current study, the NJRE-Q-R Severity scale (a well-validated measure of NJREs) was administered to 41 patients with OCD, 53 with hair-pulling disorder (HPD), 38 with gambling disorder (GD) and 43 with eating disorders (ED) along with measures of OC symptoms and general distress. In each group, NJREs were consistently associated with OC symptoms; moreover, the pattern of associations appeared coherent with the main clinical features of each disorder. The OCD group reported higher levels of NJREs severity than GD and ED, whereas there were no differences between the OCD and HPD groups. However, HPD patients did not have higher scores of NJREs severity than GD and ED counterparts. NJREs appear to be specific to OCD, but further study is needed to establish the role of this construct in OCD-related disorders.

  19. Clinical Neuropathology Practice News 4-2012: levels of evidence for brain tumor biomarkers.

    PubMed

    Berghoff, Anna Sophie; Stefanits, Harald; Heinzl, Harald; Preusser, Matthias

    2012-01-01

    The National Comprehensive Cancer Network (NCCN) recently published a task force report on the evaluation of the clinical utility of tumor biomarkers in oncology. In this report, common terminology and the use of levels of evidence scores to aid the evaluation of biomarker tests in oncology were proposed. Furthermore, the task force applied a level of evidence system to selected biomarkers of several cancer types. According to this system, the highest level of evidence, IA, is granted to a biomarker only if it has been evaluated in at least one adequately powered and specifically designed prospective controlled trial. For gliomas, only 1p/19q testing in oligodendroglial tumors was classified as IA by the NCCN task force. For all of the following biomarkers the present evidence level for clinical utility was regarded as lower than that of 1p/19q status: MGMT gene promoter methylation testing (glioblastoma), IDH mutation testing (diffusely growing gliomas), BRAF fusion testing (pilocytic astrocytoma) and CIMP testing (diffusely growing gliomas). The task force acknowledged that the exact application of levels of evidence needs further refinement. To our mind, the implementation of a brain tumor expert panel seems vital to evaluate the evidence levels of neurooncological biomarkers according to generally accepted criteria on a regular basis. Systematic identification of current research needs and widely accepted up-to-date recommendations for efficient biomarker application in everyday practice could be gained.

  20. Evidence based clinical assessment of child and adolescent social phobia: a critical review of rating scales.

    PubMed

    Tulbure, Bogdan T; Szentagotai, Aurora; Dobrean, Anca; David, Daniel

    2012-10-01

    Investigating the empirical support of various assessment instruments, the evidence based assessment approach expands the scientific basis of psychotherapy. Starting from Hunsley and Mash's evaluative framework, we critically reviewed the rating scales designed to measure social anxiety or phobia in youth. Thirteen of the most researched social anxiety scales for children and adolescents were identified. An overview about the scientific support accumulated by these scales is offered. Our main results are consistent with recent reviews that consider the Social Phobia and Anxiety Scale for Children (SPAI-C) and the Social Anxiety Scale for Adolescents (SAS-A) among the most pertinent and empirically supported measures of social anxiety for youngsters. However, after considering the existing evidence, we highly recommend another couple of scales that proved to be empirically supported (i.e., the Social Phobia Inventory-SPIN, and the Liebowitz Social Anxiety Scale for Children and Adolescents-LSAS-CA).

  1. [Exercise is medicine: development and evidence-based practice in clinical exercise physiology].

    PubMed

    Zhou, Shi

    2014-08-01

    It has been well established that appropriate physical activity and exercise play an important role in promotion of health and fitness, prevention of disease and treatment and rehabilitation of health conditions. However, practice based on scientific evidence, in respect of the role and effectiveness of exercise interventions in prevention and treatment of diseases, has only been promoted and implemented in the fields of clinical exercise physiology, public health and medicine in recent years. This brief review provides an introduction of the concept of "Exercise is Medicine", the development and evidence-based practice in Clinical Exercise Physiology, and the role and training of Clinical Exercise Physiologist in the health care system of some other countries.

  2. 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.

  3. 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.

  4. Factors associated with medical student clinical reasoning and evidence based medicine practice

    PubMed Central

    Kamei, Robert; Chan, Kenneth; Goh, Sok-Hong; Ngee, Lek

    2015-01-01

    Objectives To identify the factors associated with medical students’ clinical reasoning (CR) use and evidence-based medicine (EBM) use in the clinical setting. Methods Our cross-sectional study surveyed 44 final-year medical students at an emerging academic medical center in Singapore. We queried the students’ EBM and CR value and experiences in the classroom and clinical settings. We compared this to their perceptions of supervisors’ value and experiences using t-tests. We developed measures of teaching culture and practice culture by combining relevant questions into summary scores. Multivariate linear regression models were applied to identify factors associated with the students’ CR and EBM clinical use. Results Eighty-nine percent of students responded (n=39). Students reported valuing CR (p=0.03) and EBM (p=0.001) more than their supervisors, but practiced these skills similarly (p=0.83; p=0.82). Clinical practice culture and classroom CR experience were independently associated with students’ CR clinical use (p=0.05; p=0.04), and classroom EBM experience was independently associated with students’ EBM clinical use (p=0.03). Clinical teaching culture was not associated with students’ CR and EBM clinical use. Conclusions Our study found that medical students’ classroom experience and the clinical practice culture influenced their CR and EBM use. The clinical teaching culture did not. These findings suggest that in order to increase student CR and EBM use, in addition to providing classroom experience, medical educators may need to change the hospital culture by encouraging supervisors to use these skills in their clinical practice. PMID:26547924

  5. Restoration of posterior teeth in clinical practice: evidence base for choosing amalgam versus composite.

    PubMed

    Kovarik, Robert E

    2009-01-01

    This article reviews the current use of amalgam versus resin composite in posterior restorations and the evidence-base for choosing between these two treatment options. While much research has been published on the issue of the clinical use of amalgam versus resin composite, there are several issues that limit the true evidence-base on the subject. Furthermore, while the majority of published studies on posterior composites would seem to indicate equivalent clinical performance of resin composite to amalgam restorations, the studies that should be weighted much more heavily (randomized controlled trials) do not support the slant of the rest of the literature. As part of an evidence-based approach to private practice, clinicians need to be aware of the levels of evidence in the literature and need to properly inform patients of the true clinical outcomes that are associated with the use of amalgam versus resin composite for posterior restorations, so that patients are themselves making informed decisions about their dental care.

  6. A collaborative teaching strategy for enhancing learning of evidence-based clinical decision-making.

    PubMed

    Scott, P J; Altenburger, P A; Kean, J

    2011-01-01

    The educational literature cites a lack of student motivation to learn how to use research evidence in clinical decision-making because the students do not observe clinicians using evidence. This lack of motivation presents a challenge to educators as they seek to instill the value of evidence-based clinical decision-making (EBCD) in students. One problem is that students in entry-level programs do not have the experience needed to know what to look for, and secondly, clinical decision-making is contextually based in a patient problem. Our approach offers one solution to bridging the gap between classroom teaching and real-world implementation of EBCD through a three-phase collaborative approach. Occupational and physical therapy students are partnered with clinicians to find and appraise evidence to answer the real-world questions posed by these therapists. This paper describes the implementation of the partnership, teaching/learning outcomes, logistics, and implications for clinicians. We found this approach increased student motivation and greatly enhanced the learning experience. Future directions include implementing a framework which allows for the assessment of the strategy on the facility and creates opportunities to integrate the use of EBCD in all aspects of facility practice.

  7. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Watanabe, Sumio; Hashimoto, Etsuko; Ikejima, Kenichi; Uto, Hirofumi; Ono, Masafumi; Sumida, Yoshio; Seike, Masataka; Takei, Yoshiyuki; Takehara, Tetsuo; Tokushige, Katsutoshi; Nakajima, Atsushi; Yoneda, Masashi; Saibara, Toshiji; Shiota, Goshi; Sakaida, Isao; Nakamuta, Makoto; Mizuta, Toshihiko; Tsubouchi, Hirohito; Sugano, Kentaro; Shimosegawa, Tooru

    2015-04-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary. Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

  8. Development and validation of COMPASS: clinical evidence of orphan medicinal products – an assessment tool

    PubMed Central

    2013-01-01

    Background Rare diseases are defined as life-threatening or chronically debilitating diseases with a prevalence of 50 out of 100,000 individuals or less. Orphan medicinal products (OMPs) are intended for the treatment of rare diseases. The assessment of quality of evidence in small populations is often complex. Many generic tools are unfit. Therefore, the aim of this study was to develop and validate a new tool to assess the quality of OMPs' clinical evidence (COMPASS). Methods Firstly, a draft version of the COMPASS tool, developed by the authors and consisting of three parts, was amended based on suggestions obtained in four rounds of expert consultation. Secondly, the tool was put through three rounds of validation. The data source was information provided on the Orphanet website and in European Public Assessment Report (EPAR) document of the European Medicines Agency. Results The first pilot round revealed a high (92.2%) inter-rater agreement for part one of the tool. After further improvements, the final inter-rater agreement was 86.4% for part two (on methodological quality) and three (on quality of reporting) of the tool. The COMPASS tool does not attempt to score or rank the quality of clinical evidence, but rather to give an outline of various, key elements with respect to quality of clinical evidence of OMP studies. Conclusions The COMPASS tool can be applied to assess the quality of evidence of an OMP based on information in the registration dossier, for example by local reimbursement agencies, pharmacists or clinicians. In that way, the tool can contribute to making reimbursement and/or treatment decisions increasingly more founded on the principles of evidence-based decision making. PMID:24107467

  9. The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence.

    PubMed

    Chisari, Alberto; Pistritto, Anna Maria; Piccolo, Raffaele; La Manna, Alessio; Danzi, Gian Battista

    2016-09-06

    The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES.

  10. The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence

    PubMed Central

    Chisari, Alberto; Pistritto, Anna Maria; Piccolo, Raffaele; La Manna, Alessio; Danzi, Gian Battista

    2016-01-01

    The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES. PMID:27608017

  11. Evidence of NAO control on subsurface ice accumulation in a 1200 yr old cave-ice sequence, St. Livres ice cave, Switzerland

    NASA Astrophysics Data System (ADS)

    Stoffel, Markus; Luetscher, Marc; Bollschweiler, Michelle; Schlatter, Frédéric

    2009-07-01

    Mid-latitude ice caves are assumed to be highly sensitive to climatic changes and thus represent a potentially interesting environmental archive. Establishing a precise chronology is, however, a prerequisite for the understanding of processes driving the cave-ice mass balance and thus allows a paleoenvironmental interpretation. At St. Livres ice cave (Jura Mountains, Switzerland), subfossil trees and organic material are abundant in the cave-ice deposit, therefore allowing the dating of individual ice layers. The dendrochronological analysis of 45 subfossil samples of Norway spruce ( Picea abies (L.) Karst.) from the overhanging front of the ice outcrop as well as the dating of seven wood samples with 14C dating allowed for a reconstruction of the St. Livres cave-ice sequence and for the determination of periods of ice accumulation and ablation. Results suggest a maximal age of 1200 ± 50 14C yr BP for the observed ice sequence and indicate the presence of four major deposition gaps dated to the 14th, 15th, mid-19th and late 19th century, which can be related with periods of positive North Atlantic Oscillation anomalies (NAO+) over the winter half-year and/or anthropogenic cave-ice abstraction. Similarly, there is evidence that periods of cave-ice accumulation as observed between AD 1877-1900 and AD 1393-1415 would correspond with phases of negative NAO indices. Cave ice represents therefore an original climate archive for the winter half-year and is complementary to other continental proxies recording preferentially summer conditions (e.g., tree rings, varves).

  12. Evidence for gas accumulation beneath the surface crust driving cyclic rise and fall of the lava surface at Halema`uma`u, Kilauea Volcano

    NASA Astrophysics Data System (ADS)

    Patrick, M. R.; Orr, T. R.; Wilson, D.; Sutton, A. J.; Elias, T.; Fee, D.; Nadeau, P. A.

    2010-12-01

    The ongoing eruption in Halema`uma`u crater, at the summit of Kilauea Volcano, has surpassed the two-year mark and is characterized by lava lake activity in the vent. As of August 2010, the lava lake is about 70 m in diameter and 180 m below the rim of a narrow vent cavity. Although the explosive events that typified the first year of activity have abated, episodic rise and fall of the lava surface remains common. Cycles of rise and fall range from several minutes to eight hours in duration and are characterized by a quiescent rise phase and violent, gas-charged fall, spanning a height change of 20-30 m. Several models have been proposed to explain the cyclic rise and fall of lava surfaces at basaltic volcanoes, which in some cases is referred to as “gas pistoning”. In one model, episodic rise and fall is driven by the ascent of gas slugs from depth. In another, the cyclic behavior is driven by gas accumulation beneath the surface crust, with each cycle terminated by an abrupt failure of the crust, resulting in gas release. Seismic and infrasound data, as well as gas and webcam monitoring, at Halema`uma`u over the past two years strongly support the gas accumulation model, based on several lines of evidence. First, gas emission rates drop significantly below background levels during the rise phase, and increase dramatically during the fall phase, suggesting a process of gas buildup and release as opposed to slug flow. Second, the rise phases can last several hours, which is longer than reasonable slug ascent times. Third, the rise rate decreases over time, and in many cases plateaus, as the lava reaches its high stand, which is contrary to the exponential increase expected for gas slugs. Fourth, webcam video has captured numerous instances where rockfalls piercing the surface crust initiate gas release and lava level drop, suggestive of gas accumulation at shallow levels. Lastly, FTIR (Fourier Transform Infrared Spectroscopy) data reveal changes in gas

  13. How good is the evidence base for test selection in clinical guidelines?

    PubMed

    Misra, Shivani; Barth, Julian H

    2014-05-15

    Clinical guidelines are ubiquitous, manifold and form an integral component of evidence-based clinical practice. Guidelines on test selection are often considered a useful adjunct to aid clinical decision-making, as test selection is a complex process that is influenced by many patient, clinician and laboratory factors. However, it is important to carefully evaluate several aspects of these guidelines, which include the context of the test in the guideline, the quality of the studies underpinning recommendations, the extent of the evaluation of effectiveness (or performance) of the specific test and in the clinical pathway, its applicability and ease of implementation. A robust evaluation of a diagnostic test should incorporate several stages including evaluation in healthy, symptomatic but unaffected and affected populations, and importantly a measurement of impact on patient outcomes. Few diagnostic studies meet these criteria, and therefore crucial aspects of test evaluation are overlooked prior to incorporation into clinical guidelines. Whilst efforts are made to standardise reporting of studies, strength of evidence and quality of guidelines, further work is required to improve the quality of the diagnostic studies that formulate these guidelines. It is important that clinicians using guidelines for test selection appreciate the limitations of the diagnostic test, and the guidelines themselves.

  14. Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence

    PubMed Central

    Zschucke, Elisabeth; Gaudlitz, Katharina

    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. PMID:23412549

  15. 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

  16. Urinary tract analgesics for the treatment of patients with acute cystitis: where is the clinical evidence?

    PubMed

    Pergialiotis, Vassilis; Arnos, Pantelis; Mavros, Michael N; Pitsouni, Eleni; Athanasiou, Stavros; Falagas, Matthew E

    2012-08-01

    Acute cystitis is one of the most common health-related problems in the female population. Over the last few decades, a number of drugs labeled as 'urinary tract analgesics' were released; these are available over the counter and are gaining widespread resonance among the North American population. The main representatives of this class of drugs are phenazopyridine and methenamine hippurate. Methenamine's efficacy and side effects have been well studied in a recent systematic review. On the other hand, in contrast to its widespread use, the published clinical evidence regarding phenazopyridine's effectiveness and safety is scarce. In addition, consumers (potentially patients) appear to ignore the limitations of this kind of treatment. In this article, concerns regarding the use of over-the-counter uroanalgesics, with a focus on the relevant clinical evidence, are discussed.

  17. 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

  18. 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

  19. Evidence-based clinical practice guidelines for managing depression in persons living with HIV.

    PubMed

    Relf, Michael V; Eisbach, Shelly; Okine, Kayj Nash; Ward, Terry

    2013-01-01

    Depressive symptoms and depression are prevalent among persons living with HIV (PLWH). Depression among PLWH is associated with a lower quality of life, reduced adherence to antiretroviral treatment, poorer self-care, worsened treatment outcomes, greater impairment in social and vocational functioning, and increased social isolation. Assessment of depression in PLWH is critical to facilitate referral and management. Fortunately, two simple screening questions can be used to assess for depression, and evidence supports the effective management of depression for PLWH. First-line treatment regimens for depression include selective serotonin reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT), or a combination of SSRI and CBT. This paper examines the contemporary evidence related to depression in the context of HIV infection. A case study has been included to illustrate an application of evidence-based treatment interventions recommended for clinical practice.

  20. What type of clinical evidence is needed to assess medical devices?

    PubMed

    Tarricone, Rosanna; Boscolo, Paola Roberta; Armeni, Patrizio

    2016-09-01

    The objective of this mini-review is to discuss the role of real-world studies as a source of clinical evidence when experimental studies, such as randomised controlled trials (RCTs), are not available. Waiting for RCT evidence when the technology is diffusing could be anti-economical, inefficient from the policy perspective and methodologically questionable.We explain how real-world studies could provide relevant evidence to decision makers. Matching techniques are discussed as a viable solution for bias reduction.We describe a case study concerning a cost-effectiveness analysis based on real-world data of a technology already in use: Mitraclip combined with medical therapy versus medical therapy alone in patients with moderate-to-severe mitral regurgitation. The CEA has encountered the scepticism of most reviewers, due not to the statistical methodology but to the fact that the study was observational and not experimental. Editors and reviewers converged in considering real-world economic evaluations premature in the absence of a RCT, even if in the meantime the technology had been implanted >30 000 times. We believe there is a need to acknowledge the importance of real-world studies, and engage the scientific community in the promotion and use of clinical evidence produced through observational studies.

  1. 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

  2. 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

  3. Evolution of clinical practice guidelines: evidence supporting expanded use of medicines.

    PubMed

    Dubois, Robert W; Dean, Bonnie B

    2006-08-01

    Previous studies have shown that the primary factor underlying increased spending on pharmaceuticals has been the rising utilization of medications, rather than increases in unit drug price. This study examined the evolution of clinical practice guidelines to assess possible reasons for the rising drug volume. Clinical practice guidelines from 1970 to the present were reviewed for the six most prevalent treatable medical conditions/risk factors listed as priority areas by the Institute of Medicine. We searched the National Guidelines Clearinghouse, PubMed and Medline databases, and Web sites of relevant national organizations for US clinical practice guidelines published through January 2005. Information pertaining to the therapeutic regimen (eg, the frequency and duration of recommended treatment, when treatment should be initiated, the patient population for whom the guideline was intended) was abstracted and entered into evidence tables. Changes in guidelines were distributed across three themes that recommended evidence-based increases in medication use, including: (1) changes in the size of the treatable population; (2) changes in the number and type of recommended pharmaceutical therapeutic options, including movement from monotherapy to combination therapy, treatment of comorbidities, and use of newer types of medicines; and (3) changes in the therapeutic regimen, including a shift from episodic care to preventive and chronic care. Many of these changes point to an important, but not often noticed, addition of secondary prevention of disease effects to the objectives of medical care. These trends are likely to continue with important economic, clinical, and policy ramifications.

  4. 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

  5. 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.

  6. Evidence-Based Rationale for Ankle Cartilage Allograft Replacement: A Systematic Review of Clinical Outcomes.

    PubMed

    Johnson, Pierce; Lee, Daniel K

    2015-01-01

    The treatment of ankle arthritis remains controversial. Ankle cartilage allograft replacement is a novel and complex procedure. Many clinical studies have shown some level of promise, as well complications. We performed a systematic review of the clinical outcomes to describe and assess the different techniques and clinical outcomes for ankle cartilage allograft replacement. We performed a review of the published studies using MEDLINE(®) by way of PubMed(®) and Google Scholar(®) from January 2000 through October 2014, ranging from case reports to clinical studies. The inclusion criteria consisted of ankle cartilage allograft procedures with objective findings and clinical outcome scoring and complication and fusion rates and excluded nonallograft synthetic graft techniques, bone substitutes or expanders, review reports, and technique instructional manuals. Evidence with the combination of objective findings and clinical outcomes for all 3 type of allograft replacement (osteochondral, unipolar, and bipolar) is lacking. Several techniques for cartilage fixation have been described, including absorbable and metallic fixation. Most of the studies reported many occurrences and a variety of complications. A myriad of techniques for ankle cartilage allograft replacement exists. The results from the present systematic review of the published studies appear promising; however, the lack of statistical power and inconsistent documentation made it difficult to determine the superiority of any one intervention compared with another for the treatment of ankle arthritis.

  7. Significance of Kampo, Japanese traditional medicine, in the treatment of obesity: basic and clinical evidence.

    PubMed

    Yamakawa, Jun-Ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan () and boiogito (), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.

  8. 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

  9. 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.

  10. What clinical psychologists know about evidence-based practice: familiarity with online resources and research methods.

    PubMed

    Berke, David M; Rozell, Cassandra A; Hogan, Thomas P; Norcross, John C; Karpiak, Christie P

    2011-04-01

    Evidence-based practice (EBP) requires that practitioners routinely access, appraise, and utilize the best available research. We surveyed a representative sample of the Society of Clinical Psychology; 549 psychologists (response rate = 46%) reported their frequency of engaging in EBP when offering psychological services, rated their current knowledge of 12 online research resources, and evaluated their current knowledge of 12 research methods and designs. These psychologists reported, on average, using EBP in 73.1% of their psychological services. With the exception of PsycINFO and MEDLINE, clinical psychologists related low to moderate knowledge of online research resources. By contrast, these psychologists reported considerable knowledge of most research methods and designs, except for odds ratios and structural equation modeling. Psychologists' theoretical orientation, clinical experience, and employment setting predicted knowledge of both online resources and research designs. We discuss the educational and practice ramifications of these results.

  11. Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis.

    PubMed

    Mostovaya, Ira M; Blankestijn, Peter J; Bots, Michiel L; Covic, Adrian; Davenport, Andrew; Grooteman, Muriel P C; Hegbrant, Jörgen; Locatelli, Francesco; Vanholder, Raymond; Nubé, Menso J

    2014-03-01

    The general objective assigned to the European DIALysis (EUDIAL) Working Group by the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on hemodiafiltration (HDF) therapies. A EUDIAL consensus conference was held in Paris on 13 October 2011 to discuss definitions, safety standards, clinical outcome and educational issues. Recently, the first report of the EUDIAL group was published, revisiting the definition, dose quantification, and safety of HDF. Since the meeting in Paris, new evidence has become available regarding the clinical benefits of HDF. This is the second report of the expert group in which the relation between HDF and clinical outcomes is systematically reviewed and analyzed, with emphasis on the relation between achieved convection volume and treatment effect.

  12. Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: A review of the available evidence.

    PubMed

    Stefani, Stefania; Campanile, Floriana; Santagati, Maria; Mezzatesta, Maria Lina; Cafiso, Viviana; Pacini, Giovanni

    2015-09-01

    The emergence of glycopeptide reduced susceptibility and resistance in Staphylococcus aureus strains is a growing clinical problem that poses significant clinical challenges in treatment. Its development is a complex and novel process involving many subtle physiological changes in the micro-organism. Daptomycin is the first cyclic lipopeptide approved for clinical use. Unlike most other antimicrobials, a trend towards increased daptomycin resistance has not been reported, although several cases of daptomycin non-susceptibility have been reported. The present review will present the available evidence on daptomycin resistance of S. aureus, with particular attention to its development. In addition to a literature overview, we have compiled the reported cases of daptomycin non-susceptibility to shed light on possible clinical mechanisms of resistance. In the 36 reports describing 62 clinical cases, infections caused by meticillin-resistant S. aureus (MRSA) strains with a vancomycin minimum inhibitory concentration (MIC) between 1mg/L and 2mg/L often led to vancomycin treatment failure, which may be associated with the development of non-susceptibility to daptomycin. Additional evidence suggests that underdosage of daptomycin is an important clinical aspect that merits further study. The current analysis highlights the importance of determining the MIC when using vancomycin to treat patients with severe S. aureus infections and that when failure is suspected, testing for heterogeneous vancomycin-intermediate S. aureus (hVISA) may also be necessary. Whilst further investigation is needed, it can be hypothesised that MRSA strains become hVISA during prolonged bacteraemia, which may predispose to the development of daptomycin resistance.

  13. Radiologists’ perspectives about evidence-based medicine and their clinical practice: a semistructured interview study

    PubMed Central

    Tong, Allison; Mahady, Suzanne E; Craig, Jonathan C; Lau, Gabes; Peduto, Anthony J; Loy, Clement

    2014-01-01

    Objectives To describe radiologist's attitudes and perspectives on evidence-based medicine (EBM) and their practice. Design Face-to-face semistructured interviews, thematic analysis. Setting 24 institutions across six Australian states and New Zealand. Transcripts were imported into HyperRESEARCH software and thematically analysed. Participants 25 radiologists. Results Six themes were identified: legitimising decisions (validated justification, prioritising patient preferences, reinforcing protocols), optimising outcomes (ensuring patient safety, maximising efficiency), availability of access (requiring immediacy, inadequacy of evidence, time constraints, proximity of peer networks, grasping information dispersion), over-riding pragmatism (perceptibly applicability, preserving the art of medicine, technical demands), limited confidence (conceptual obscurity, reputation-based trust, demands constant practice, suspicion and cynicism), and competing powers (hierarchical conflict, prevailing commercial interests). Conclusions Radiologists believe EBM can support clinical decision-making for optimal patient outcomes and service efficiency but feel limited in their capacities to assimilate and apply EBM in practice. Improving access to evidence, providing ongoing education and training supplemented with practical tools for appraising evidence; and developing evidence-based guidelines and protocols may enhance feasibility and promote the confidence and skills among radiologists in applying EBM in radiology practice for better patient care. PMID:25500161

  14. Combining randomized and non-randomized evidence in clinical research: a review of methods and applications.

    PubMed

    Verde, Pablo E; Ohmann, Christian

    2015-03-01

    Researchers may have multiple motivations for combining disparate pieces of evidence in a meta-analysis, such as generalizing experimental results or increasing the power to detect an effect that a single study is not able to detect. However, while in meta-analysis, the main question may be simple, the structure of evidence available to answer it may be complex. As a consequence, combining disparate pieces of evidence becomes a challenge. In this review, we cover statistical methods that have been used for the evidence-synthesis of different study types with the same outcome and similar interventions. For the methodological review, a literature retrieval in the area of generalized evidence-synthesis was performed, and publications were identified, assessed, grouped and classified. Furthermore real applications of these methods in medicine were identified and described. For these approaches, 39 real clinical applications could be identified. A new classification of methods is provided, which takes into account: the inferential approach, the bias modeling, the hierarchical structure, and the use of graphical modeling. We conclude with a discussion of pros and cons of our approach and give some practical advice.

  15. Evidence that the major metabolites accumulating in medium-chain acyl-CoA dehydrogenase deficiency disturb mitochondrial energy homeostasis in rat brain.

    PubMed

    Schuck, Patrícia Fernanda; Ferreira, Gustavo da Costa; Tonin, Anelise Miotti; Viegas, Carolina Maso; Busanello, Estela Natacha Brandt; Moura, Alana Pimentel; Zanatta, Angela; Klamt, Fábio; Wajner, Moacir

    2009-11-03

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an inherited metabolic disorder of fatty acid oxidation in which the affected patients predominantly present high levels of octanoic (OA) and decanoic (DA) acids and their glycine and carnitine by-products in tissues and body fluids. It is clinically characterized by episodic encephalopathic crises with coma and seizures, as well as by progressive neurological involvement, whose pathophysiology is poorly known. In the present work, we investigated the in vitro effects of OA and DA on various parameters of energy homeostasis in mitochondrial preparations from brain of young rats. We found that OA and DA markedly increased state 4 respiration and diminished state 3 respiration as well as the respiratory control ratio, the mitochondrial membrane potential and the matrix NAD(P)H levels. In addition, DA-elicited increase in oxygen consumption in state 4 respiration was partially prevented by atractyloside, indicating the involvement of the adenine nucleotide translocator. OA and DA also reduced ADP/O ratio, CCCP-stimulated respiration and the activities of respiratory chain complexes. The data indicate that the major accumulating fatty acids in MCADD act as uncouplers of oxidative phosphorylation and as metabolic inhibitors. Furthermore, DA, but not OA, provoked a marked mitochondrial swelling and cytochrome c release from mitochondria, reflecting a permeabilization of the inner mitochondrial membrane. Taken together, these data suggest that OA and DA impair brain mitochondrial energy homeostasis that could underlie at least in part the neuropathology of MCADD.

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

    PubMed Central

    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.

    2012-01-01

    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 evidence-based administrative strategies and methods utilized by clinic staff to effectively implement a comprehensive evidence-based treatment for substance abuse (i.e., Family Behavior Therapy). The basic structure of the clinic, standardized behavioral methods associated with its day-to-day operations, and maintenance of treatment integrity are delineated. Infrastructural systems are underscored, including clinical record keeping, quality assurance, and staff management. PMID:19535671

  17. 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

  18. 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.

  19. 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.

  20. 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

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusions 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

  2. Cyanide in human disease: a review of clinical and laboratory evidence.

    PubMed

    Wilson, J

    1983-01-01

    Experimental cyanide exposure in animals causes demyelination and circumstantial clinical and laboratory evidence suggest that there are human parallels. In Leber's hereditary optic atrophy there appears to be a defect in the conversion of cyanide to thiocyanate because of deficient rhodanese activity. For transmitters of the disease smoking carries the risk of blindness and in the most severely affected patients, there is diffuse neurological disease. It is possible that other hereditary optic atrophies (dominant and recessive) may also reflect inborn errors of cyanide metabolism. In the retrobulbar neuritis and optic atrophy of vitamin B12 deficiency there may be a conditional abnormality of cyanide metabolism in smokers, and likewise in so-called tobacco-alcohol amblyopia in which there are more complex nutritional deficiencies. Epidemiological evidence (differing sex ratios, excess of smokers) indicates that defective cyanide metabolism may contribute to the development of sub-acute combined degeneration of the cord in vitamin B12 deficiency. In protein-malnourished populations consuming large amounts of cyanide or cyanogens, viz. in tropical Africa where the staple diet includes cassava containing large amounts of linamarin, similar maladies occur as acquired disorders. There may be a similar explanation for lathyrism. The known pathways of human cyanide metabolism are reviewed and evidence supporting the clinical data is presented.

  3. Incorporating equity into developing and implementing for evidence-based clinical practice guidelines.

    PubMed

    Eslava-Schmalbach, Javier; Sandoval-Vargas, Gisella; Mosquera, Paola

    2011-04-01

    Clinical practice guidelines (CPG) are useful tools for clinical decision making, processes standardization and quality of care improvements. The current General Social Security and Health System (GSSHS) in Colombia is promoting the initiative of developing and implementing CPG based on evidence in order to improve efficiency and quality of care. The reduction of inequalities in health should be an objective of the GSSHS. The main propose of this analysis is to argue why it is necessary to consider the incorporation of equity considerations in the development and implementation of clinical practice guidelines based on the evidence. A series of reflections were made. Narrative description was used for showing the arguments that support the main findings. Among them are: 1. Differential effectiveness by social groups of interventions could diminish final effectiveness of CPG in the GSSHS; 2. To not consider geographical, ethnic, socioeconomic, cultural and access diversity issues within the CPG could have a potential negative impacts of the CPG; 3. Overall effectiveness of GPC could be better if equity issues are included in the quality verification checklist of the guideline questions; 4. Incorporating equity issues in the process of developing CPG could be cost effective, because improve overall effectiveness of CPG. Conclusions To include equity issues in CPG can help in achieving more equitable health outcomes. From this point of view CPG could be key tools to promote equity in care and health outcomes.

  4. Clinical Decision Velocity is Increased when Meta-search Filters Enhance an Evidence Retrieval System

    PubMed Central

    Coiera, Enrico; Westbrook, Johanna I.; Rogers, Kris

    2008-01-01

    Objective To test whether the use of an evidence retrieval system that uses clinically targeted meta-search filters can enhance the rate at which clinicians make correct decisions, reduce the effort involved in locating evidence, and provide an intuitive match between clinical tasks and search filters. Design A laboratory experiment under controlled conditions asked 75 clinicians to answer eight randomly sequenced clinical questions, using one of two randomly assigned search engines. The first search engine Quick Clinical (QC) was equipped with meta-search filters (the combined use of meta-search and search filters) designed to answer typical clinical questions e.g., treatment, diagnosis, and the second ‘library model’ system (LM) offered free access to an identical evidence set with no filter support. Measurements Changes in clinical decision making were measured by the proportion of correct post-search answers provided to questions, the time taken to answer questions, and the number of searches and links to documents followed in a search session. The intuitive match between meta-search filters and clinical tasks was measured by the proportion and distribution of filters selected for individual clinical questions. Results Clinicians in the two groups performed equally well pre-search. Post search answers improved overall by 21%, with 52.2% of answers correct with QC and 54.7% with LM (χ2 = 0.33, df = 1, p > 0.05). Users of QC obtained a significantly greater percentage of their correct answers within the first two minutes of searching compared to LM users (QC 58.2%; LM 32.9%; χ2 = 19.203, df = 1, p < 0.001). There was a statistical difference for QC and LM survival curves, which plotted overall time to answer questions, irrespective of answer (Wilcoxon, p = 0.019) and for the average time to provide a correct answer (Wilcoxon, p = 0.006). The QC system users conducted significantly fewer searches per scenario (m = 3.0 SD = 1.15 versus m = 5.5 SD1.97, t = 6

  5. 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

  6. Development of EBM-CDSS (Evidence-Based Clinical Decision Support System) to AIG Prognostication in Terminally Ill Patients

    DTIC Science & Technology

    2016-03-01

    1 Award Number: W81-XWH-09-2-0175 TITLE: Development of EBM-CDSS (Evidence-Based Clinical Decision Support System) to AIG Prognostication in...From - To) 25Sep2009 - 31Dec2015 4. TITLE AND SUBTITLE Development of EBM-CDSS (Evidence-Based Clinical Decision Support System) to AIG Prognostication...health.usf.edu 4 14. ABSTRACT Goal of the project is to develop an Evidence-based Clinical Decision Support (CDSS-EBM) system and make it available at the point

  7. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    PubMed

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  8. 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

  9. Robotic Surgery in Women With Ovarian Cancer: Surgical Technique and Evidence of Clinical Outcomes.

    PubMed

    Minig, Lucas; Padilla Iserte, Pablo; Zorrero, Cristina; Zanagnolo, Vanna

    2016-01-01

    Robotic surgery is a new technology that has been progressively implemented to treat endometrial and cervical cancer. However, the use of robotic surgery for ovarian cancer is limited to a few series of cases and comparative studies with laparoscopy or laparotomy. The technical issues concerning robotic surgery, as well as clinical evidence, are described in this review. Robotic surgery in early stage, advanced stage, and relapsed ovarian cancer is discussed separately. In conclusion, evidence regarding the use of robotic-assisted surgical treatment for women with ovarian cancer is still scarce, but its use is progressively growing. Robotic-assisted staging in selected patients with early stage disease has an important role in referral institutions when well-trained gynecologists perform surgeries. However, minimally invasive surgery in patients with advanced stage or relapsed ovarian cancer requires further investigation, even in selected cases.

  10. The role of setting for ketamine abuse: clinical and preclinical evidence.

    PubMed

    De Luca, Maria Teresa; Meringolo, Maria; Spagnolo, Primavera Alessandra; Badiani, Aldo

    2012-01-01

    Drug abuse is often seen as a unitary phenomenon, partly as a result of the discovery over the past three decades of shared mechanisms of action for addictive substances. Yet the pattern of drug taking is often very different from drug to drug. This is particularly evident in the case of 'club drugs', such as ketamine. Although the number of ketamine abusers is relatively small in the general population, it is quite substantial in some settings. In particular, ketamine abuse is almost exclusively limited to clubs and large music parties, which suggests a major role of context in modulating the reward effects of this drug. This review focuses on recent preclinical and clinical findings, including previously unpublished data, that provide evidence that, even under controlled conditions, ketamine reward is a function of the setting of drug taking.

  11. Current Issues and Clinical Evidence in Tumor-Infiltrating Lymphocytes in Breast Cancer

    PubMed Central

    Ahn, Sung Gwe; Jeong, Joon; Hong, SoonWon; Jung, Woo Hee

    2015-01-01

    With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2–positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer. PMID:26278518

  12. Burn center journal club promotes clinical research, continuing education, and evidence-based practice.

    PubMed

    Fowler, Laura; Gottschlich, Michele M; Kagan, Richard J

    2013-01-01

    The purpose of this study was to characterize the structure, policy, implementation, and outcome measures of a burn team journal club to assess its effectiveness in promoting multidisciplinary education relative to research competency, clinical knowledge, and evidence-based practice. After 2 years of a new multidisciplinary format, an anonymous quality assurance survey was distributed to staff members of a regional pediatric burn center to evaluate the impact of the journal club on clinical and research indicators. The 24 journal club meetings evaluated in this study included a variety of topics, among which were wound healing, infection, nutrition, metabolism, sleep, medications, alternative medicine, research compliance, and child abuse. The speakers included a variety of hospital personnel: 26% researchers, 23% physicians, 20% registered nurses, and 31% other disciplines and attendance mean was 29 participants per session (range 17-50). Survey results from 30 respondents indicated that 100% judged the program to be valuable to personal educational needs and 83% indicated that format did not warrant change. According to self-report data, the journal club enhanced medical knowledge (90%), patient care (73%), research competency (70%), critical thinking (63%), and evidence-based practice (63%). Results indicate that the journal club program was well received by participants, and promoted enhanced knowledge and improved patient care. In the future, barriers to research initiatives and integration of research findings into practice warrant follow-up study. Journal club should be incorporated into the learning curriculum of burn practitioners as a means to promote critical thinking, research competency, and evidence-based clinical practice.

  13. [Clinical trials: prerequisite of evidence-based oncology: reality, perspectives and a new tool recruited--the Internet].

    PubMed

    Mross, K; März, W

    2001-02-01

    Scientifically sound clinical research is an undispensable prerequisite to establish innovative therapeutic principles, to support applications for marketing authorization of proprietary new drugs, to advance therapeutic results in cancer therapy, and the only route towards an evidence-based clinical oncology at the advent of the 21st century. Treatment of cancer patients based on scientific evidence derived from clinical studies outperforms compassionate individual therapeutic decisions with a lack of evidence, whenever such evidence is available or whenever a clinical trial is addressing the clinical situation that must be addressed for an individual patient. A stable trend towards improved survival of cancer patients was first observed in 1999. The advent of new technologies of drug design, the integration of pharmacology, genomics and DNA microarray chip technologies will produce a myriad of new anticancer drugs with promising potential for cancer therapy that need to be tested in the clinical setting without delay. To match that challenge, clinical oncology must streamline the laborious process of conducting clinical trials. The process of planning, multicenter coordinating, recruiting, treatment, analyzing, and reporting of clinical trial results must be further optimized. The best possible quality control of all steps of that process is a prerequisite to motivate patients to participate in clinical trials of cancer therapy - always one of the most promising treatment options for patients seeking the best possible cancer care. At the same time as the internet goes mainstream and cancer care information is ubiquitously laymanized and dispersed via cancer cybermedicine, clinical researchers may employ the internet to exchange information, facilitate conduction of clinical trials, and facilitate recruitment to clinical studies via web-based trial registries. This will be more than an incremental step forward to deliver the best possible clinical care towards the

  14. Clinical postconference pedagogy: exploring evidence-based practice with millennial-inspired "Building Blocks".

    PubMed

    Schams, Kristin A; Kuennen, Jackie K

    2012-01-01

    This article reports an innovative teaching strategy consisting of learning units whereby students come to postconference sessions prepared to share evidence-based practice (EBP) information associated with upcoming laboratory concepts, discover relationships among laboratory concepts and current nursing practice, and associate personal clinical experiences with the practice environment. This strategy, named "Building Blocks," represents one method to transform nursing education into a more active process, and also has the potential to prepare graduates who can function in a dynamic health care environment incorporating EBP.

  15. Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence.

    PubMed

    Jensen, Bjorn; Chen, Jeffrey; Furnish, Tim; Wallace, Mark

    2015-10-01

    Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics. The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems. The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes. Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.

  16. Botulinum toxin in the management of chronic migraine: clinical evidence and experience

    PubMed Central

    Escher, Claus M; Paracka, Lejla; Dressler, Dirk; Kollewe, Katja

    2016-01-01

    Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox®) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM. PMID:28382110

  17. 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

  18. Clinical guidelines for occupational lifting in pregnancy: evidence summary and provisional recommendations

    PubMed Central

    MacDonald, Leslie A.; Waters, Thomas R.; Napolitano, Peter G.; Goddard, Donald E.; Ryan, Margaret A.; Nielsen, Peter; Hudock, Stephen D.

    2015-01-01

    Empirically based lifting criteria established by the National Institute for Occupational Safety and Health (NIOSH) to reduce the risk of overexertion injuries in the general US working population were evaluated for application to pregnant workers. This report proposes criteria to guide decisions by medical providers about permissible weights for lifting tasks performed at work over the course of an uncomplicated pregnancy. Our evaluation included an extensive review of the literature linking occupational lifting to maternal and fetal health. Although it has been 29 years since the American Medical Association’s Council on Scientific Affairs published its report on the Effects of Pregnancy on Work Performance, these guidelines continue to influence clinical decisions and workplace policies. Provisional clinical guidelines derived from the NIOSH lifting criteria that account for recent evidence for maternal and fetal health are presented and aim to improve the standard of care for pregnant workers. PMID:23467051

  19. In search of evidence-based treatment for concussion: characteristics of current clinical trials

    PubMed Central

    Burke, Matthew J.; Fralick, Michael; Nejatbakhsh, Nasrin; Tartaglia, Maria C.; Tator, Charles H.

    2015-01-01

    Abstract Objective: To assess the characteristics of current clinical trials investigating the treatment of concussion. Background: Recent systematic literature reviews have concluded that there is minimal evidence to support any specific treatment for concussion, including the principles of return-to-activity protocols such as type or duration of rest. Design/methods: Clinical trial data was extracted from Clinicaltrials.gov and seven additional World Health Organization primary registries. The trial databases were accessed up until 3 October 2013. This study used search terms of ‘concussion’ or ‘mild traumatic brain injury’ (mTBI) and filtered for interventional trials. Trials that were terminated, already published or not interventional trials of concussion/mTBI were excluded. Results: Of the 142 concussion/mTBI interventional clinical trials identified, 71 met inclusion criteria. Trials had a median estimated enrolment of 60 participants. There was a wide-range of treatments studied, including cognitive/behavioural therapies (28.2%), medications (28.2%), devices (11.3%), dietary supplements (8.5%), return-to-activity/rest (1.4%) and others (22.4%). Heterogeneity among trials for concussion identification/diagnosis and primary outcomes utilized was evident. Symptom-based questionnaires (39.4%) and neuropsychological tests (28.2%) were the most common outcome measures. Conclusions: Diverse, potentially promising therapeutics are currently being studied for the treatment of concussion. However, several deficiencies were identified including a paucity of trials addressing return-to-activity principles. Also, small sample size and trial heterogeneity may threaten scientific evaluation and subsequent clinical application. PMID:25383510

  20. The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

    PubMed Central

    de León-Casasola, Oscar A; Mayoral, Victor

    2016-01-01

    Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. PMID:26929664

  1. 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.

  2. A language activity monitor for supporting AAC evidence-based clinical practice.

    PubMed

    Hill, K J; Romich, B A

    2001-01-01

    Augmentative and alternative communication (AAC) evidence-based practice requires the collection and analysis of performance data. This article presents the development, evaluation, and application of automated performance monitoring tools for use in clinical practice. Language activity monitoring (LAM) is the systematic data collection of the actual language activity of an individual who relies on AAC. Work completed to date includes the development and evaluation of the language activity monitor function, which now is commercially available in three forms: (1) a standard feature built into modern high performance AAC systems, (2) an external add-on package for use with older AAC devices based on synthetic speech, and (3) software that allows the personal computer to serve as an LAM in the clinical environment. The LAM records the time and content of language events (the generation of one or more letters or words). A logging protocol suitable for clinical application has been in use since late 1998. The logged data is uploaded periodically to a computer for editing, analysis, and the generation of a summary measure report. The applications of this work in the areas of clinical service delivery are presented.

  3. 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

  4. 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

  5. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    PubMed

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.

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

    PubMed

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

    2016-07-29

    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.

  7. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence

    PubMed Central

    Li, Shasha; Zaninotto, Ana Luiza; Neville, Iuri Santana; Paiva, Wellingson Silva; Nunn, Danuza; Fregni, Felipe

    2015-01-01

    Traumatic brain injury (TBI) remains the main cause of disability and a major public health problem worldwide. This review focuses on the neurophysiology of TBI, and the rationale and current state of evidence of clinical application of brain stimulation to promote TBI recovery, particularly on consciousness, cognitive function, motor impairments, and psychiatric conditions. We discuss the mechanisms of different brain stimulation techniques including major noninvasive and invasive stimulations. Thus far, most noninvasive brain stimulation interventions have been nontargeted and focused on the chronic phase of recovery after TBI. In the acute stages, there is limited available evidence of the efficacy and safety of brain stimulation to improve functional outcomes. Comparing the studies across different techniques, transcranial direct current stimulation is the intervention that currently has the higher number of properly designed clinical trials, though total number is still small. We recognize the need for larger studies with target neuroplasticity modulation to fully explore the benefits of brain stimulation to effect TBI recovery during different stages of recovery. PMID:26170670

  8. Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study

    PubMed Central

    Harrison, M; Newman, S; Hall-Craggs, M; Fowler, C; Miller, R; Kendall, B; Paley, M; Wilkinson, I; Sweeney, B; Lunn, S; Carter, S; Williams, I

    1998-01-01

    OBJECTIVES—To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression.
METHODS—The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics.
RESULTS—This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, , and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background.
CONCLUSIONS—Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychogical assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

 PMID:9728940

  9. Mutations in RIT1 cause Noonan syndrome – additional functional evidence and expanding the clinical phenotype

    PubMed Central

    Koenighofer, Martin; Hung, Christina Y.; McCauley, Jacob L.; Dallman, Julia; Back, Emma J.; Mihalek, Ivana; Gripp, Karen W.; Sol-Church, Katia; Rusconi, Paolo; Zhang, Zhaiyi; Shi, Geng-Xian; Andres, Douglas A.; Bodamer, Olaf A.

    2015-01-01

    RASopathies are a clinically heterogeneous group of conditions caused by mutations in one of sixteen proteins in the RAS-MAPK pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and, p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins, however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. PMID:25959749

  10. Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of the Clinical Evidence.

    PubMed

    Vaughn, Alexandra R; Branum, Amy; Sivamani, Raja K

    2016-08-01

    Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti-neoplastic properties. Growing evidence shows that an active component of turmeric, curcumin, may be used medically to treat a variety of dermatologic diseases. This systematic review was conducted to examine the evidence for the use of both topical and ingested turmeric/curcumin to modulate skin health and function. The PubMed and Embase databases were systematically searched for clinical studies involving humans that examined the relationship between products containing turmeric, curcumin, and skin health. A total of 234 articles were uncovered, and a total of 18 studies met inclusion criteria. Nine studies evaluated the effects of ingestion, eight studies evaluated the effects of topical, and one study evaluated the effects of both ingested and topical application of turmeric/curcumin. Skin conditions examined include acne, alopecia, atopic dermatitis, facial photoaging, oral lichen planus, pruritus, psoriasis, radiodermatitis, and vitiligo. Ten studies noted statistically significant improvement in skin disease severity in the turmeric/curcumin treatment groups compared with control groups. Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved. Copyright © 2016 John Wiley & Sons, Ltd.

  11. [The Usage of Auricular Acupressure in Clinical Nursing and Evidence-Based Research].

    PubMed

    Cheng, Jui-Fen; Lo, Chyi; Tzeng, Ya-Ling

    2015-12-01

    Auricular acupressure is a non-invasive physiotherapy that was developed based on the traditional Chinese meridian theory. Because it is non-invasive, simple to implement, and easy to learn, and because it presents minimal side effects and may be executed independently, this therapy may be used as an alternative or auxiliary approach to symptom management as well as to self-care. The increasing support for auricular acupressure from evidence-based research in Taiwan and elsewhere offers the opportunity to include auricular acupressure as a treatment option in evidence-based nursing interventions. Because nursing education in Taiwan is guided by Western medical concepts and principles, most nurses are not familiar with auricular acupressure, which is derived from traditional Chinese medicine. Therefore, this article not only systemically introduces the definition and theoretical basis of auricular acupressure but also includes the principles and application-related knowledge. Furthermore, this article analyzes the common problems encountered in auricular acupressure research in order to improve the familiarity of nurses with this therapy, to provide references for clinical application, and to provide a basis for designing new evidence-based nursing research efforts.

  12. 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

  13. 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…

  14. 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

  15. Clinical and ultrasonographic evidence of a proximal positional fault of the radius. A case report.

    PubMed

    Malo-Urriés, Miguel; Hidalgo-García, César; Bueno-Gracia, Elena; Estébanez-de-Miguel, Elena; Lucha-López, Orosia; Tricás-Moreno, José Miguel

    2014-06-01

    Positional faults are considered a possible underlying mechanism mimicking the symptoms of a joint sprain. Despite numerous clinical studies indicating the presence of positional faults, there is limited evidence of imaging studies confirming positional faults. This case report is a preliminary study that offers clinical and ultrasonographic evidence of a proximal positional fault of the radius, treated successfully with manual therapy techniques. Three weeks after a bike fall on the outstretched hand, the patient in this study presented with right wrist pain and a lack of progress with conventional conservative treatment (NSAIDs, rest and immobilization). Clinical findings indicating a proximal positional fault of the radius included pain during active pronation increased by associating a passive movement of the radius in a proximal direction and it was reduced by associating a passive movement of the radius in a distal direction. Ultrasonographic (US) images showed a reduction of radio-capitellar distance on the right side (11.4 mm) compared to the left side (13.3 mm). A positive response with a distal mobilization of the radius supported the proximal positional fault of the radius. After two manual therapy sessions, the patient had recovered normal asymptomatic function. The outcomes used to assess function and pain were active pronation range of motion, the Spanish version of the DASH questionnaire and a 0-10 numeric pain rating scale. Each measure was conducted prior and after each treatment session and one week post treatment. The patient was re-examined at 6 months follow-up, during which US images, demonstrated a normalization of the right radio-capitellar distance.

  16. Significance of Kampo, Japanese Traditional Medicine, in the Treatment of Obesity: Basic and Clinical Evidence

    PubMed Central

    Yamakawa, Jun-ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan (防風通聖散) and boiogito (防己黄耆湯), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine. PMID:23662155

  17. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders.

    PubMed

    Caliceti, Cristiana; Franco, Placido; Spinozzi, Silvia; Roda, Aldo; Cicero, Arrigo F G

    2016-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.

  18. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies

    PubMed Central

    Stuchlik, Ales; Radostová, Dominika; Hatalova, Hana; Vales, Karel; Nekovarova, Tereza; Koprivova, Jana; Svoboda, Jan; Horacek, Jiri

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1–3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD. PMID:27833539

  19. Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

    PubMed Central

    Neto, Fani L; Borges, Gisela; Torres-Sanchez, Sonia; Mico, Juan A; Berrocoso, Esther

    2011-01-01

    Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis. PMID:22654714

  20. The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management

    PubMed Central

    Nocerino, Rita; Pezzella, Vincenza; Cosenza, Linda; Amoroso, Antonio; Di Scala, Carmen; Amato, Francesco; Iacono, Giuseppe; Berni Canani, Roberto

    2015-01-01

    Food allergies (FAs) are an increasing problem in Western countries, affecting up to 10% of young children. FAs are frequently associated with gastrointestinal manifestations. The role of FAs as a potential causative factor for infantile colic (IC) is still controversial. We report the most recent evidence on the pathogenesis, clinical and diagnostic aspects of FA-induced infantile colic (IC) and suggest a stepwise diagnostic approach. We selected articles on clinical and immunologic features, pathogenesis and management of FAs and IC from of 1981 to 2015. Original and review articles were identified through selective searches performed on PubMed, using the following terms: colic, infantile colic, food allergy and infantile colic, infantile colic treatment. The possible relationship between FAs and IC derives from the presence of dysmotility with visceral hypersensitivity and dysbiosis, demonstrated in both conditions, and the clinical response to dietary interventions. Unfortunately, the design of the studies, poor characterization of atopy and different dietary approaches limit the understanding of the importance of FAs in subjects with IC. The role of FAs in IC subjects without other symptoms of atopy remains controversial. However, where there is a suspicion of FAs, a short trial with an extensively hydrolyzed cow’s proteins formula or, if breast fed, with maternal elimination diet may be considered a reasonable option. PMID:25808260

  1. Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions.

    PubMed

    Pilotto, Alberto; Cella, Alberto; Pilotto, Andrea; Daragjati, Julia; Veronese, Nicola; Musacchio, Clarissa; Mello, Anna Maria; Logroscino, Giancarlo; Padovani, Alessandro; Prete, Camilla; Panza, Francesco

    2017-02-01

    Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.

  2. Accumulation of clinically relevant antibiotic-resistance genes, bacterial load, and metals in freshwater lake sediments in Central Europe.

    PubMed

    Devarajan, Naresh; Laffite, Amandine; Graham, Neil D; Meijer, Maria; Prabakar, Kandasamy; Mubedi, Josué I; Elongo, Vicky; Mpiana, Pius T; Ibelings, Bastiaan Willem; Wildi, Walter; Poté, John

    2015-06-02

    Wastewater treatment plants (WWTP) receive the effluents from various sources (communities, industrial, and hospital effluents) and are recognized as reservoir for antibiotic-resistance genes (ARGs) that are associated with clinical pathogens. The aquatic environment is considered a hot-spot for horizontal gene transfer, and lake sediments offer the opportunity for reconstructing the pollution history and evaluating the impacts. In this context, variation with depth and time of the total bacterial load, the abundance of faecal indicator bacteria (FIB; E. coli and Enterococcus spp. (ENT)), Pseudomonas spp., and ARGs (blaTEM, blaSHV, blaCTX-M, blaNDM, and aadA) were quantified in sediment profiles of different parts of Lake Geneva using quantitative PCR. The abundance of bacterial marker genes was identified in sediments contaminated by WWTP following eutrophication of the lake. Additionally, ARGs, including the extended-spectrum ß-lactam- and aminoglycoside-resistance genes, were identified in the surface sediments. The ARG and FIB abundance strongly correlated (r ≥ 0.403, p < 0.05, n = 34) with organic matter and metal concentrations in the sediments, indicating a common and contemporary source of contamination. The contamination of sediments by untreated or partially treated effluent water can affect the quality of ecosystem. Therefore, the reduction of contaminants from the source is recommended for further improvement of water quality.

  3. Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

    PubMed Central

    Virhammar, Johan; Nyholm, Dag

    2016-01-01

    The duration of action of oral levodopa becomes shorter as Parkinson’s disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa–carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in ‘off’ time and ‘on’ time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment. PMID:28344656

  4. 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…

  5. A survey of the perceptions and behaviors of chiropractic interns pertaining to evidence-based principles in clinical decision making

    PubMed Central

    Dane, Dawn E.; Dane, Andrew B.; Crowther, Edward R.

    2016-01-01

    Objective: This study explored how chiropractic interns applied evidenced-based concepts, the sources of evidence they used, and how useful they perceived these sources to be in clinical decision making. Methods: A questionnaire containing 13 items in a Likert 5-point scale was administered to 28 chiropractic interns to gather information on the evidence types they commonly accessed and their perceived usefulness of these sources in clinical decision making. The interns were in the 8th semester of the training program. Results: There was a 93% (n = 26) response rate. Clinical guidelines were rated as the most helpful resource in clinical decision making (81%), followed by lecture materials (77%), journals (54%), databases (50%), and textbooks (35%). Students recognized scientific evidence as the most important aspect in clinical decision making. They found their personal experience and the views of their clinician to be equally important and patient preference the least. Conclusion: Interns routinely employed high-quality levels of evidence in clinical decision making. They also considered their early, limited clinical experience as important as that of their clinical supervisor in decision making. This finding should be investigated further. PMID:27389528

  6. 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…

  7. Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Evidence-Based Clinical Practice Guideline

    PubMed Central

    Herdman, Susan J.; Whitney, Susan L.; Cass, Stephen P.; Clendaniel, Richard A.; Fife, Terry D.; Furman, Joseph M.; Getchius, Thomas S. D.; Goebel, Joel A.; Shepard, Neil T.; Woodhouse, Sheelah N.

    2016-01-01

    Background: Uncompensated vestibular hypofunction results in postural instability, visual blurring with head movement, and subjective complaints of dizziness and/or imbalance. We sought to answer the question, “Is vestibular exercise effective at enhancing recovery of function in people with peripheral (unilateral or bilateral) vestibular hypofunction?” Methods: A systematic review of the literature was performed in 5 databases published after 1985 and 5 additional sources for relevant publications were searched. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case control series, and case series for human subjects, published in English. One hundred thirty-five articles were identified as relevant to this clinical practice guideline. Results/Discussion: Based on strong evidence and a preponderance of benefit over harm, clinicians should offer vestibular rehabilitation to persons with unilateral and bilateral vestibular hypofunction with impairments and functional limitations related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) as specific exercises for gaze stability. Based on moderate evidence, clinicians may offer specific exercise techniques to target identified impairments or functional limitations. Based on moderate evidence and in consideration of patient preference, clinicians may provide supervised vestibular rehabilitation. Based on expert opinion extrapolated from the evidence, clinicians may prescribe a minimum of 3 times per day for the performance of gaze stability exercises as 1 component of a home exercise program. Based on expert opinion extrapolated from the evidence (range of supervised visits: 2-38 weeks, mean = 10 weeks), clinicians may consider providing adequate supervised vestibular rehabilitation sessions for the

  8. 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…

  9. 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…

  10. A Review of the Evidence for Overlap between Urological and Non-urological Unexplained Clinical Conditions

    PubMed Central

    Rodríguez, María Ángeles Bullones; Afari, Niloofar; Buchwald, Dedra

    2010-01-01

    Purpose Unexplained clinical conditions share common features, such as pain, fatigue, disability out of proportion to physical examination findings, inconsistent laboratory abnormalities, and an association with stress and psychosocial factors. In this literature review, we examine the extent of the overlap among urological and non-urological unexplained clinical conditions characterized by pain, note the limitations of previous research, and suggest several possible explanatory models. Materials & Methods Using hallmark symptoms and syndromes as search terms, a search of 12 databases identified 1,037 full-length published articles in 8 languages from 1966 to April, 2008. The search focused on the overlap of chronic pelvic pain, interstitial cystitis, painful bladder syndrome, chronic prostatitis/chronic pelvic pain syndrome, or vulvodynia, with fibromyalgia, chronic fatigue syndrome, temporomandibular disorder, or irritable bowel syndrome. Information on authorship, type of case and control groups, eligibility criteria, case definitions, study methods, and major findings were abstracted. Results The literature suggests considerable comorbidity between urological and non-urological unexplained clinical conditions. The most robust evidence for overlap was for irritable bowel syndrome and urological unexplained syndromes, with some estimates of up to 79% comorbidity between chronic pelvic pain and symptoms of irritable bowel syndrome. However, most studies were limited by methodological problems, such as varying case definitions and selection of control subjects. Conclusions Overlap between urological and selected non-urological unexplained clinical conditions is substantial. Future research should focus on using standardized definitions and rigorously designed and well-controlled studies to further assess comorbidity, clarify the magnitude of the association, and examine common pathophysiological mechanisms. PMID:19758633

  11. Clinical neuropathology practice guide 3-2013: levels of evidence and clinical utility of prognostic and predictive candidate brain tumor biomarkers.

    PubMed

    Berghoff, Anna S; Stefanits, Harald; Woehrer, Adelheid; Heinzl, Harald; Preusser, Matthias; Hainfellner, Johannes A

    2013-01-01

    A large number of potential tissue biomarkers has been proposed for brain tumors. However, hardly any have been adopted for routine clinical use, so far. For most candidate biomarkers substantial controversy exists with regard to their usefulness in clinical practice. The multidisciplinary neurooncology taskforce of the Vienna Comprehensive Cancer Center Central Nervous System Unit (CCC-CNS) addressed this issue and elaborated a four-tiered levels-of-evidence system for assessing analytical performance (reliability of test result) and clinical performance (prognostic or predictive) based on consensually defined criteria. The taskforce also consensually agreed that only biomarker candidates should be considered as ready for clinical use, which meet defined quality standards for both, analytical and clinical performance. Applying this levels-of-evidence system to MGMT, IDH1, 1p19q, Ki67, MYCC, MYCN and β-catenin, only immunohistochemical IDH1 mutation testing in patients with diffuse gliomas is supported by sufficient evidence in order to be unequivocally qualified for clinical use. For the other candidate biomarkers lack of published evidence of sufficiently high analytical test performance and, in some cases, also of clinical performance limits evidence-based confirmation of their clinical utility. For most of the markers, no common standard of laboratory testing exists. We conclude that, at present, there is a strong need for studies that specifically address the analytical performance of candidate brain tumor biomarkers. In addition, standardization of laboratory testing is needed. We aim to regularly challenge and update the present classification in order to systematically clarify the current translational status of candidate brain tumor biomarkers and to identify specific research needs for accelerating the translational pace.

  12. Tips for teaching evidence-based medicine in a clinical setting: lessons from adult learning theory. Part one.

    PubMed

    Das, Kausik; Malick, Sadia; Khan, Khalid S

    2008-10-01

    Evidence-based medicine (EBM) is an indispensable tool in clinical practice. Teaching and training of EBM to trainee clinicians is patchy and fragmented at its best. Clinically integrated teaching of EBM is more likely to bring about changes in skills, attitudes and behaviour. Provision of evidence-based health care is the most ethical way to practice, as it integrates up-to-date, patient-oriented research into the clinical decision making process, thus improving patients' outcomes. In this article, we aim to dispel the myth that EBM is an academic and statistical exercise removed from practice by providing practical tips for teaching the minimum skills required to ask questions and critically identify and appraise the evidence and presenting an approach to teaching EBM within the existing clinical and educational training infrastructure.

  13. Mepolizumab for severe refractory eosinophilic asthma: evidence to date and clinical potential

    PubMed Central

    Menzella, Francesco; Lusuardi, Mirco; Galeone, Carla; Taddei, Sofia; Facciolongo, Nicola; Zucchi, Luigi

    2016-01-01

    Severe asthma is characterized by major impairment of quality of life, poor symptom control and frequent exacerbations. Inflammatory, clinical and causative factors identify different phenotypes and endotypes of asthma. In the last few years, new treatment options have allowed for targeted treatments according to the different phenotypes of the disease. To accurately select a specific treatment for each asthmatic variant, the identification of appropriate biomarkers is required. Eosinophilic asthma is a distinct phenotype characterized by thickening of the basement membrane and corticosteroid responsiveness. This review reports the latest evidence on an anti-IL-5 monoclonal antibody, mepolizumab, a new and promising biological agent recently approved by the FDA specifically for the treatment of severe eosinophilic refractory asthma. PMID:27803792

  14. Clinical utility of trabectedin for the treatment of ovarian cancer: current evidence

    PubMed Central

    Mascilini, Floriana; Amadio, Giulia; Di Stefano, Maria Grazia; Ludovisi, Manuela; Di Legge, Alessia; Conte, Carmine; De Vincenzo, Rosa; Ricci, Caterina; Masciullo, Valeria; Salutari, Vanda; Scambia, Giovanni; Ferrandina, Gabriella

    2014-01-01

    Among the pharmaceutical options available for treatment of ovarian cancer, attention has been increasingly focused on trabectedin (ET-743), a drug which displays a unique mechanism of action and has been shown to be active in several human malignancies. Currently, single agent trabectedin is approved for treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, and in association with pegylated liposomal doxorubicin for treatment of patients with relapsed partially platinum-sensitive ovarian cancer. This review aims at summarizing the available evidence about the clinical role of trabectedin in the management of patients with epithelial ovarian cancer. Novel perspectives coming from a better understanding of trabectedin mechanisms of action and definition of patients subgroups likely susceptible to benefit of trabectedin treatment are also presented. PMID:25050069

  15. Finding the evidence: resources and skills for locating information on clinical effectiveness.

    PubMed

    Bidwell, S R

    2004-12-01

    Limited time and lack of knowledge about where and how to search for information often present barriers to practitioners who want to locate current best evidence for treating their patients. There is as yet no single place they can go to get an answer to all their questions. High quality clinical studies are difficult to filter out from the mass of information on large databases, and secondary resources of evaluated information are dispersed over hundreds of Internet sites worldwide. This overview presents a practical guide for the busy practitioner who searches only occasionally and needs to maximise the time spent. Major collections of secondary resources are identified and their individual features described briefly. Following this, several services using PubMed are outlined that automatically apply filters for studies with high quality research design. Further sources of information and assistance are listed for those who wish to learn more.

  16. Caring For Evidence: Research and Care in an Obesity Outpatient Clinic.

    PubMed

    Felder, Kay; Felt, Ulrike; Penkler, Michael

    2016-01-01

    In recent years, there has been a substantial increase in bariatric surgery rates. This form of obesity treatment is often subjected to the critique that it turns patients into passive objects of medical intervention. Similarly, efforts to 'rationalize' medicine, as in evidence-based medicine, are sometimes denounced for imposing a 'one-size-fits-all' approach that neglects patient diversity. We argue that these critiques fail to do justice to the complexities of actual care situations. In our ethnographic study of a project for bariatric pre- and aftercare, we show how research protocols not only close down but also open up spaces for patient-centered care. Despite professional cautions, experiences of stigma and broader imaginations of biomedical care often lead patients to embrace surgery as a treatment conceptualized as a technological fix. We argue that investigations of how research and clinical practice intertwine need to be both empirically grounded and sensitive to wider societal contexts.

  17. 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

  18. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines.

    PubMed

    Badesch, David B; Abman, Steven H; Simonneau, Gerald; Rubin, Lewis J; McLaughlin, Vallerie V

    2007-06-01

    A consensus panel convened by the American College of Chest Physicians developed guidelines for the treatment of pulmonary arterial hypertension (PAH) that were published in 2004. Subsequently, several important clinical trials have been published, and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues. This article, taking into consideration studies published prior to September 1, 2006, provides an update to the previously published guidelines. The original guidelines have been summarized, a discussion of new studies has been added, and the treatment algorithm has been revised to take into account recent developments in therapy. This update provides evidence-based treatment recommendations for physicians involved in the care of patients with PAH. Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended.

  19. Therapeutic approach to treating patients with BRAF-mutant lung cancer: latest evidence and clinical implications

    PubMed Central

    de Langen, Adrianus J.; Smit, Egbert F.

    2016-01-01

    Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC. In this review we discuss the latest evidence on the treatment of BRAF-mutated NSCLC, including tumor biology, targeted treatment with BRAF and MEK inhibitors, therapeutic resistance and strategies to overcome resistance. PMID:28203297

  20. WIC in Your Neighborhood: New Evidence on the Impacts of Geographic Access to Clinics

    PubMed Central

    Rossin-Slater, Maya

    2013-01-01

    A large body of evidence indicates that conditions in-utero and health at birth matter for individuals’ long-run outcomes, suggesting potential value in programs aimed at pregnant women and young children. This paper uses a novel identification strategy and data from birth and administrative records over 2005–2009 to provide causal estimates of the effects of geographic access to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). My empirical approach uses within-ZIP-code variation in WIC clinic presence together with maternal fixed effects, and accounts for the potential endogeneity of mobility, gestational-age bias, and measurement error in gestation. I find that access to WIC increases food benefit take-up, pregnancy weight gain, birth weight, and the probability of breastfeeding initiation at the time of hospital discharge. The estimated effects are strongest for mothers with a high school education or less, who are most likely eligible for WIC services. PMID:24043906

  1. Bilingual Children with Primary Language Impairment: Issues, Evidence and Implications for Clinical Actions

    PubMed Central

    Kohnert, Kathryn

    2010-01-01

    A clear understanding of how to best provide clinical serves to bilingual children with suspected or confirmed primary language impairment (PLI) is predicated on understanding typical development in dual-language learners as well as the PLI profile. This article reviews general characteristics of children learning two languages, including three that challenge the diagnosis and treatment of PLI; uneven distribution of abilities in the child's two languages, cross-linguistic associations within bilingual learners, and individual variation in response to similar social circumstances. The diagnostic category of PLI (also referred to in the literature as specific language impairment or SLI) is described with attention to how language impairment, in the face of otherwise typical development, manifests in children learning two languages. Empirical evidence related to differential diagnosis of PLI in bilingual children is then reviewed and issues related to the generalization of treatment gains in dual-language learners with PLI are introduced. PMID:20371080

  2. Clinical evidence on high flow oxygen therapy and active humidification in adults.

    PubMed

    Gotera, C; Díaz Lobato, S; Pinto, T; Winck, J C

    2013-01-01

    Recently there has been growing interest in an alternative to conventional oxygen therapy: the heated, humidified high flow nasal cannula oxygen therapy (HFNC). A number of physiological effects have been described with HFNC: pharyngeal dead space washout, reduction of nasopharyngeal resistance, a positive expiratory pressure effect, an alveolar recruitment, greater humidification, more comfort and better tolerance by the patient, better control of FiO2 and mucociliary clearance. There is limited experience of HFNC in adults. There are no established guidelines or decision-making pathways to guide use of the HFNC therapy for adults. In this article we review the existing evidence of HFNC oxygen therapy in adult patients, its advantages, limitations and the current literature on clinical applications. Further research is required to determine the long-term effect of this therapy and identify the adult patient population to whom it is most beneficial.

  3. Effects of Education Programs on Evidence-Based Practice Implementation for Clinical Nurses.

    PubMed

    Sim, Jae Youn; Jang, Keum Seong; Kim, Nam Young

    2016-08-01

    This study was conducted to identify the effectiveness of an education program for evidence-based practice (EBP) implementation of clinical nursing. EBP knowledge/skill, attitude, and belief; information search ability; and EBP implementation were significantly higher in the experimental group than in the control group. Furthermore, the effect on implementation was maintained at week 4 and week 8, indicating that the education program practically promotes the EBP implementation of nurses. Results confirm that the education program for EBP implementation is critical and the continuous education program is an essential part of EBP implementation. Also, to promote EBP implementation and disseminate it to nursing organizations, an immediate concern should be the cultivation of mentors for EBP and fortification of the belief and ability regarding EBP implementation. J Contin Educ Nurs. 2016;47(8):363-371.

  4. Management of type 2 diabetes: more evidence is required to address the clinical and contextual facets.

    PubMed

    Hernandez-Jimenez, Sergio; Aguilar-Salinas, Carlos A; Mehta, Roopa; Rull, Juan A; Gómez-Pérez, Francisco J

    2011-03-01

    Evidence based medicine has changed the manner in which medicine is practiced and learned. Epidemiological studies, meta-analyses and systematic reviews have been used to create algorithms for the treatment of hyperglycemia in patients with type 2 diabetes. Recently, several randomized controlled trials (i.e. ACCORD, ADVANCE, VADT) have generated new and valuable information regarding the benefits and risks of achieving optimal glucose control. As a result, guidelines and algorithms have been updated. However, many aspects remain controversial. In this article, the clinical implications of the existing guidelines are critically analyzed. The limitations of the current guidelines include the lack of applicability to relevant diabetic subgroups, the exclusion of important factors that modify the therapeutic response to glucose-lowering agents and the limited recognition of the importance of the socioeconomic situation on treatment efficacy. Many subgroups of patients have not been included in the studies used to generate recommendations. There is insufficient evidence to support the use of current treatment recommendations in patients with early onset type 2 diabetes, patients with advanced microvascular complications, and the elderly with or without chronic complications. The characteristics of the candidates for conservative or intensive treatment are poorly defined. Interventions are recommended without considering clinical variables (i.e. obesity, time since diagnosis or prolonged exposure to hyperglycemia) that may modify treatment efficacy and the occurrence of side effects. Finally, no consideration is given to the socioeconomic context of the population in which the guidelines are to be applied. In summary, this manuscript highlights the key areas which require further work. If these issues are adequately addressed, the guidelines for the management of type 2 diabetes will be relevant and applicable to all diabetic groups.

  5. Implementation outcomes of evidence-based quality improvement for depression in VA community based outpatient clinics

    PubMed Central

    2012-01-01

    Background Collaborative-care management is an evidence-based practice for improving depression outcomes in primary care. The Department of Veterans Affairs (VA) has mandated the implementation of collaborative-care management in its satellite clinics, known as Community Based Outpatient Clinics (CBOCs). However, the organizational characteristics of CBOCs present added challenges to implementation. The objective of this study was to evaluate the effectiveness of evidence-based quality improvement (EBQI) as a strategy to facilitate the adoption of collaborative-care management in CBOCs. Methods This nonrandomized, small-scale, multisite evaluation of EBQI was conducted at three VA Medical Centers and 11 of their affiliated CBOCs. The Plan phase of the EBQI process involved the localized tailoring of the collaborative-care management program to each CBOC. Researchers ensured that the adaptations were evidence based. Clinical and administrative staff were responsible for adapting the collaborative-care management program for local needs, priorities, preferences and resources. Plan-Do-Study-Act cycles were used to refine the program over time. The evaluation was based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) Framework and used data from multiple sources: administrative records, web-based decision-support systems, surveys, and key-informant interviews. Results Adoption: 69.0% (58/84) of primary care providers referred patients to the program. Reach: 9.0% (298/3,296) of primary care patients diagnosed with depression who were not already receiving specialty care were enrolled in the program. Fidelity: During baseline care manager encounters, education/activation was provided to 100% (298/298) of patients, barriers were assessed and addressed for 100% (298/298) of patients, and depression severity was monitored for 100% (298/298) of patients. Less than half (42.5%, 681/1603) of follow-up encounters during the acute stage were completed

  6. Timing of Decompressive Surgery of Spinal Cord after Traumatic Spinal Cord Injury: An Evidence-Based Examination of Pre-Clinical and Clinical Studies

    PubMed Central

    Furlan, Julio C.; Noonan, Vanessa; Cadotte, David W.

    2011-01-01

    Abstract While the recommendations for spine surgery in specific cases of acute traumatic spinal cord injury (SCI) are well recognized, there is considerable uncertainty regarding the role of the timing of surgical decompression of the spinal cord in the management of patients with SCI. Given this, we sought to critically review the literature regarding the pre-clinical and clinical evidence on the potential impact of timing of surgical decompression of the spinal cord on outcomes after traumatic SCI. The primary literature search was performed using MEDLINE, CINAHL, EMBASE, and Cochrane databases. A secondary search strategy incorporated articles referenced in prior meta-analyses and systematic and nonsystematic review articles. Two reviewers independently assessed every study with regard to eligibility, level of evidence, and study quality. Of 198 abstracts of pre-clinical studies, 19 experimental studies using animal SCI models fulfilled our inclusion and exclusion criteria. Despite some discrepancies in the results of those pre-clinical studies, there is evidence for a biological rationale to support early decompression of the spinal cord. Of 153 abstracts of clinical studies, 22 fulfilled the inclusion and exclusion criteria. While the vast majority of the clinical studies were level-4 evidence, there were two studies of level-2b evidence. The quality assessment scores varied from 7 to 25 with a mean value of 12.41. While 2 of 22 clinical studies assessed feasibility and safety, 20 clinical studies examined efficacy of early surgical intervention to stabilize and align the spine and to decompress the spinal cord; the most common definitions of early operation used 24 and 72 h after SCI as timelines. A number of studies indicated that patients who undergo early surgical decompression can have similar outcomes to patients who received a delayed decompressive operation. However, there is evidence to suggest that early surgical intervention is safe and feasible

  7. A clinical comparison of the efficacy of an electromechanical flossing device or manual flossing in affecting interproximal gingival bleeding and plaque accumulation.

    PubMed

    Anderson, N A; Barnes, C M; Russell, C M; Winchester, K R

    1995-01-01

    This one-month clinical trial was designed to compare the effect of an electromechanical flossing device and manual flossing on reducing interproximal gingival bleeding and plaque accumulation in a cohort of 60 healthy adults. After baseline evaluation of interproximal gingival bleeding, soft tissue trauma and plaque, patients were randomly assigned to one of the two experimental groups, given flossing instructions, and had their teeth cleaned. At 30 days all three clinical parameters were again evaluated. The results showed a reduction in GI from baseline to follow-up in each group. This effect is significant (p<0.0001) in the analysis of variance. There was no overall difference in the groups (p=0.93). There was no difference in the reduction in GI from baseline to follow-up between the two groups (p=0.91); interaction). As with the GI, there was a significant reduction in PI from baseline to follow-up in each group (p<0.0001). There was no overall difference between the groups (p=0.24). There was no difference in the reduction in PI from baseline to follow-up between the two groups (p=0.59; interaction). No soft tissue trauma was noted at the baseline examination or at the follow-up examination after 30 days.

  8. A review of the clinical evidence for exercise in osteoarthritis of the hip and knee.

    PubMed

    Bennell, Kim L; Hinman, Rana S

    2011-01-01

    Osteoarthritis (OA) is a chronic joint disease with the hip and knee being commonly affected lower limb sites. Osteoarthritis causes pain, stiffness, swelling, joint instability and muscle weakness, all of which can lead to impaired physical function and reduced quality of life. This review of evidence provides recommendations for exercise prescription in those with hip or knee OA. A narrative review was performed. Conservative non-pharmacological strategies, particularly exercise, are recommended by all clinical guidelines for the management of OA and meta-analyses support these exercise recommendations. Aerobic, strengthening, aquatic and Tai chi exercise are beneficial for improving pain and function in people with OA with benefits seen across the range of disease severities. The optimal exercise dosage is yet to be determined and an individualized approach to exercise prescription is required based on an assessment of impairments, patient preference, co-morbidities and accessibility. Maximising adherence is a key element dictating success of exercise therapy. This can be enhanced by the use of supervised exercise sessions (possibly in class format) in the initial exercise period followed by home exercises. Bringing patients back for intermittent consultations with the exercise practitioner, or attendance at "refresher" group exercise classes may also assist long-term adherence and improved patient outcomes. Few studies have evaluated the effects of exercise on structural disease progression and there is currently no evidence to show that exercise can be disease modifying. Exercise plays an important role in managing symptoms in those with hip and knee OA.

  9. [Selective digestive decontamination. Why don't we apply the evidence in the clinical practice?].

    PubMed

    Taylor, N; van Saene, H K F; Abella, A; Silvestri, L; Vucic, M; Peric, M

    2007-04-01

    Selective digestive decontamination (SDD) is a prophylactic strategy whose objective is to reduce the incidence of infections, mainly mechanical ventilation associated pneumonia in patients who require intensive cares, preventing or eradicating the oropharyngeal and gastrointestinal carrier state of potentially pathogenic microorganisms. Fifty-four randomized clinical trials (RCTs) and 9 meta-analysis have evaluated SDD. Thirty eight RCTs show a significant reduction of the infections and 4 of mortality. All the meta-analyses show a significant reduction of the infections and 5 out of the 9 meta-analyses report a significant reduction in mortality. Thus, 5 patients from the ICU with SDD must be treated to prevent pneumonia and 12 patients from the ICU should be treated to prevent one death. The data that show benefit of the SDD on mortality have an evidence grade 1 or recommendation grade A (supported by at least two level 1 investigations). The aim of this review is to explain the pathogeny of infections in critical patients, describe selective digestive decontamination, analyze the evidence available on it efficacy and the potential adverse effects and discuss the reasons published by the experts who advise against the use of SDD, even though it is recognized as the best intervention evaluated in intensive cares to reduce morbidity and mortality of the infections.

  10. The current evidence base for the clinical nurse leader: a narrative review of the literature.

    PubMed

    Bender, Miriam

    2014-01-01

    The clinical nurse leader (CNL) is a relatively new nursing role, introduced in 2003 through the American Association of Colleges of Nursing (AACN). A narrative review of the extant CNL literature was conducted with the aim of comprehensively summarizing the broad and methodologically diverse CNL evidence base. The review included 25 implementation reports, 1 CNL job analysis, 7 qualitative and/or survey studies, and 3 quantitative studies. All CNL implementation reports and studies described improved care quality outcomes after introduction of the role into a care delivery microsystem. Despite preliminary evidence supporting the CNL as an innovative new nursing role capable of consistently improving care quality wherever it is implemented, CNLs are still struggling to define the role to themselves and to the health care spectrum at large. Although the AACN CNL White Paper provides a concise model for CNL educational curriculum and end competencies, there is a compelling need for further research to substantively delineate the CNL role in practice, define care delivery structures and processes that influence CNL integration, and develop indicators capable of capturing CNL-specific contributions to improved care quality.

  11. Evidence-based practice guidelines--one way to enhance clinical practice.

    PubMed

    Bailes, Barbara K

    2002-06-01

    Abdominoplasty and liposuction guidelines are just two of the guidelines that can be accessed and used to enhance patient care. Guidelines also can be used to increase your knowledge about many other health care topics. The NGC has approved guidelines for managing chronic pain, as well as guidelines on chronic diseases (e.g., diabetes mellitus, hypertension, chronic obstructive pulmonary disease). Many patients have chronic diseases, and you or your family members also may be affected by chronic disorders. These guidelines provide you with a quick overview of evidence-based treatment protocols. These guidelines are not a panacea for evidence-based practice, but using them is one way that perioperative nurses can enhance their clinical skills. Though not everyone has personal Internet access, most health care facilities do or can make access a reality. Other options include medical or public libraries. Then one simply has to access the NGC web site and join other professionals in improving the quality and timeliness of patient care.

  12. 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.

  13. Yoga for the Treatment of Insomnia among Cancer Patients: Evidence, Mechanisms of Action, and Clinical Recommendations.

    PubMed

    Mustian, Karen M; Janelsins, Michelle; Peppone, Luke J; Kamen, Charles

    Up to 90% of cancer patients report symptoms of insomnia during and after treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, and waking up too early. Insomnia symptoms are among the most prevalent, distressing and persistent cancer- and cancer treatment-related toxicities reported by patients, and can be severe enough to increase cancer morbidity and mortality. Despite the ubiquity of insomnia symptoms, they are under-screened, under-diagnosed, and under-treated in cancer patients. When insomnia symptoms are identified, providers are hesitant to prescribe, and patients are hesitant to take pharmaceuticals due to polypharmacy concerns. In addition, sleep medications do not cure insomnia. Yoga is a well-tolerated mode of exercise with promising evidence for its efficacy in improving insomnia symptoms among cancer patients. This article reviews existing clinical research on the effectiveness of yoga for treating insomnia among cancer patients. The article also provides clinical recommendations for prescribing yoga for the treatment of insomnia in this population.

  14. Escitalopram--translating molecular properties into clinical benefit: reviewing the evidence in major depression.

    PubMed

    Leonard, Brian; Taylor, David

    2010-08-01

    The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents.

  15. State of the Art in Degenerative Cervical Myelopathy: An Update on Current Clinical Evidence.

    PubMed

    Wilson, Jefferson R; Tetreault, Lindsay A; Kim, Jun; Shamji, Mohammed F; Harrop, James S; Mroz, Thomas; Cho, Samuel; Fehlings, Michael G

    2017-03-01

    Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction that confronts clinicians on a daily basis. Research performed over the past few decades has provided improved insight into the diagnosis, evaluation, and treatment of this disorder. We aim to provide clinicians with an update regarding the state of the art in DCM, focusing on more recent research pertaining to pathophysiology, natural history, treatment, consideration of the minimally symptomatic patient, surgical outcome prediction, and outcome measurement. Current concepts of pathophysiology focus on the combination of static and dynamic elements leading to breakdown of the blood-spinal cord barrier at the site of compression resulting in local inflammation, cellular dysfunction, and apoptosis. With respect to treatment, although there is a dearth of high-quality studies comparing surgical to nonoperative treatment, several large prospective studies have recently associated surgical management with clinically and statistically significant improvement in functional, disability, and quality of life outcome at long-term follow-up. When selecting the specific surgical intervention for a patient with DCM, anterior (discectomy, corpectomy, hybrid discectomy/corpectomy), posterior (laminectomy and fusion, laminoplasty), and combined approaches may be considered as options depending on the specifics of the patient in question; evidence supporting each of these approaches is reviewed in detail. Recently developed clinical prediction models allow for accurate forecasting of postoperative outcomes, permitting enhanced communication and management of patient expectations in the preoperative setting. Finally, an overview of outcome measures recommended for use in the assessment of DCM patients is provided.

  16. Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma.

    PubMed

    Hou, Shenda; Zhou, Shiyu; Qin, Zhen; Yang, Liu; Han, Xiangkun; Yao, Shun; Ji, Hongbin

    2017-03-08

    Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs. In the liver kinase B1 (official name STK11)-deficient mouse model, lung ADC can progressively transdifferentiate to SCC through pathologically mixed adenosquamous cell carcinoma as the intermediate status. Mechanistic studies further identify essential roles of extracellular matrix remodeling and metabolic reprogramming during this phenotypic transition. Small molecular compounds, including lysyl oxidase inhibitors and reactive oxygen species-inducing reagents such as phenformin, significantly accelerate the transition from lung ADC to SCC and thus confer lung tumors with drug resistance. Consistent with these findings, recent clinical studies have shown that epidermal growth factor receptor-mutant lung ADC can transdifferentiate to SCC in relapsed cancer patients. Together, these data support that this phenotypic transition from lung ADC to SCC might represent a novel mechanism for drug resistance. This review will summarize our current understanding of the transdifferentiation from lung ADC to SCC.

  17. Influence of Amino Acids in Dairy Products on Glucose Homeostasis: The Clinical Evidence.

    PubMed

    Chartrand, Dominic; Da Silva, Marine S; Julien, Pierre; Rudkowska, Iwona

    2017-02-20

    Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods.

  18. The Paradox of ApoA5 Modulation of Triglycerides: Evidences from Clinical and Basic Research

    PubMed Central

    Garelnabi, Mahdi; Lor, Kenton; Jin, Jun; Chai, Fei; Santanam, Nalini

    2012-01-01

    Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), although its plasma concentration is very low compared to other known apoproteins. Over the years, researchers have attempted to elucidate the molecular mechanisms by which ApoA5 regulates plasma TG in vivo. Though still under debate, two theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of very low-density lipoprotein (VLDL), the major carrier of TGs. This review will summarize the basic and clinical studies that have attempted to describe the importance of ApoA5 in TG metabolism. Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity). ApoA5 is also highly expressed during liver regeneration and is an acute phase protein associated with HDL which was independent of its effects on TG metabolism. Conclusion Despite considerable evidences available from clinical and basic research studies, on the role of ApoA5 in TG metabolism and its indirect link to metabolic diseases, additional investigations are needed to understand the paradoxical role of this important apoprotein shown modulated by diet and from it polymorphism variants. PMID:23000317

  19. Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid

    PubMed Central

    Osti, Leonardo; Buda, Matteo; Buono, Angelo Del; Osti, Raffaella; Massari, Leo

    2015-01-01

    Summary Purpose the aim of this quantitative review is to document potential benefit and adverse effects of hyaluronic acid (HA) injection into the shoulder with rotator cuff tears. Methods a systematic literature search was performed in english PubMed, Medline, Ovid, Google Scholar and Embase databases using the combined key words “hyaluronic acid”, “rotator cuff tear”, “hyaluronate”, “shoulder”, “viscosupplementation”, with no limit regarding the year of publication. Articles were included if they reported data on clinical and functional outcomes, complications in series of patients who had undergone HA injection for management of rotator cuff tears. Two Authors screened the selected articles for title, abstract and full text in accordance with predefined inclusion and exclusion criteria. The papers were accurately analyzed focusing on objective rating scores reported. Results a total of 11 studies, prospective, 7 were randomized were included by full text. A total of 1102 patients were evaluated clinically after different HA injection compare with corticosteroid injection, physically therapies, saline solution injection and control groups. The use of HA in patients with rotator cuff tears improve VAS and functional score in all trials that we have analyzed. Conclusion intra-articular injection with HA is effective in reducing pain and improving function in shoulder with rotator cuff tears and without severe adverse reaction. Level of evidence Level I. PMID:26958534

  20. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin

    PubMed Central

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H.; Lokkegaard, Annemette; Marti, Maria J.; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D.; Zoons, Evelien; Ferreira, Joaquim J.; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A. J.

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored. PMID:28286494

  1. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin.

    PubMed

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H; Lokkegaard, Annemette; Marti, Maria J; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D; Zoons, Evelien; Ferreira, Joaquim J; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A J

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored.

  2. First line fertility treatment strategies regarding IUI and IVF require clinical evidence.

    PubMed

    Bahadur, G; Homburg, R; Muneer, A; Racich, P; Alangaden, T; Al-Habib, A; Okolo, S

    2016-06-01

    The advent of intracytoplasmic sperm injection (ICSI) has contributed to a significant growth in the delivery of assisted conception technique, such that IVF/ICSI procedures are now recommended over other interventions. Even the UK National Institute for Health Care Excellence (NICE) guidelines controversially recommends against intrauterine insemination (IUI) procedures in favour of IVF. We reflect on some of the clinical, economic, financial and ethical realities that have been used to selectively promote IVF over IUI, which is less intrusive and more patient friendly, obviates the need for embryo storage and has a global application. The evidence strongly favours IUI over IVF in selected couples and national funding strategies should include IUI treatment options. IUI, practised optimally as a first line treatment in up to six cycles, would also ease the pressures on public funds to allow the provision of up to three IVF cycles for couple who need it. Fertility clinics should also strive towards ISO15189 accreditation standards for basic semen diagnosis for male infertility used to triage ICSI treatment, to reduce the over-diagnosis of severe male factor infertility. Importantly, there is a need to develop global guidelines on inclusion policies for IVF/ICSI procedures. These suggestions are an ethically sound basis for constructing the provision of publicly funded fertility treatments.

  3. Yoga for the Treatment of Insomnia among Cancer Patients: Evidence, Mechanisms of Action, and Clinical Recommendations

    PubMed Central

    Mustian, Karen M.; Janelsins, Michelle; Peppone, Luke J.; Kamen, Charles

    2015-01-01

    Up to 90% of cancer patients report symptoms of insomnia during and after treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, and waking up too early. Insomnia symptoms are among the most prevalent, distressing and persistent cancer- and cancer treatment-related toxicities reported by patients, and can be severe enough to increase cancer morbidity and mortality. Despite the ubiquity of insomnia symptoms, they are under-screened, under-diagnosed, and under-treated in cancer patients. When insomnia symptoms are identified, providers are hesitant to prescribe, and patients are hesitant to take pharmaceuticals due to polypharmacy concerns. In addition, sleep medications do not cure insomnia. Yoga is a well-tolerated mode of exercise with promising evidence for its efficacy in improving insomnia symptoms among cancer patients. This article reviews existing clinical research on the effectiveness of yoga for treating insomnia among cancer patients. The article also provides clinical recommendations for prescribing yoga for the treatment of insomnia in this population. PMID:25861453

  4. Physician Professional Satisfaction and Area of Clinical Practice: Evidence from an Integrated Health Care Delivery System

    PubMed Central

    Caloyeras, John P; Kanter, Michael; Ives, Nicole; Kim, Chong Y; Kanzaria, Hemal K; Berry, Sandra H; Brook, Robert H

    2016-01-01

    Context: For health care reform to succeed, health care systems need a professionally satisfied primary care workforce. Evidence suggests that primary care physicians are less satisfied than those in other medical specialties. Objective: To assess three domains of physician satisfaction by area of clinical practice among physicians practicing in an established integrated health system. Design: Cross-sectional online survey of all Southern California Permanente Medical Group (SCPMG) partner and associate physicians (N = 1034) who were primarily providing clinic-based care in 1 of 4 geographically and operationally distinct Kaiser Permanente Southern California Medical Centers. Main Outcome Measures: Primary measure was satisfaction with one’s day-to-day professional life as a physician. Secondary measures were satisfaction with quality of care and income. Results: Of the 636 physicians responding to the survey (61.5% response rate), on average, 8 in 10 SCPMG physicians reported satisfaction with their day-to-day professional life as a physician. Primary care physicians were only minimally less likely to report being satisfied (difference of 8.2–9.5 percentage points; p < 0.05) than were other physicians. Nearly all physicians (98.2%) were satisfied with the quality of care they are able to provide. Roughly 8 in 10 physicians reported satisfaction with their income. No differences were found between primary care physicians and those in other clinical practice areas regarding satisfaction with quality of care or income. Conclusion: It is possible to create practice settings, such as SCPMG, in which most physicians, including those in primary care, experience high levels of professional satisfaction. PMID:27057819

  5. Electroencephalographic neurofeedback: Level of evidence in mental and brain disorders and suggestions for good clinical practice.

    PubMed

    Micoulaud-Franchi, J-A; McGonigal, A; Lopez, R; Daudet, C; Kotwas, I; Bartolomei, F

    2015-12-01

    The technique of electroencephalographic neurofeedback (EEG NF) emerged in the 1970s and is a technique that measures a subject's EEG signal, processes it in real time, extracts a parameter of interest and presents this information in visual or auditory form. The goal is to effectuate a behavioural modification by modulating brain activity. The EEG NF opens new therapeutic possibilities in the fields of psychiatry and neurology. However, the development of EEG NF in clinical practice requires (i) a good level of evidence of therapeutic efficacy of this technique, (ii) a good practice guide for this technique. Firstly, this article investigates selected trials with the following criteria: study design with controlled, randomized, and open or blind protocol, primary endpoint related to the mental and brain disorders treated and assessed with standardized measurement tools, identifiable EEG neurophysiological targets, underpinned by pathophysiological relevance. Trials were found for: epilepsies, migraine, stroke, chronic insomnia, attentional-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, major depressive disorder, anxiety disorders, addictive disorders, psychotic disorders. Secondly, this article investigates the principles of neurofeedback therapy in line with learning theory. Different underlying therapeutic models are presented didactically between two continua: a continuum between implicit and explicit learning and a continuum between the biomedical model (centred on "the disease") and integrative biopsychosocial model of health (centred on "the illness"). The main relevant learning model is to link neurofeedback therapy with the field of cognitive remediation techniques. The methodological specificity of neurofeedback is to be guided by biologically relevant neurophysiological parameters. Guidelines for good clinical practice of EEG NF concerning technical issues of electrophysiology and of learning are suggested. These require validation by

  6. Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence.

    PubMed

    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 foodstuffs 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 available

  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. Deficiencies in the transfer and availability of clinical trials evidence: a review of existing systems and standards

    PubMed Central

    2012-01-01

    Background Decisions concerning drug safety and efficacy are generally based on pivotal evidence provided by clinical trials. Unfortunately, finding the relevant clinical trials is difficult and their results are only available in text-based reports. Systematic reviews aim to provide a comprehensive overview of the evidence in a specific area, but may not provide the data required for decision making. Methods We review and analyze the existing information systems and standards for aggregate level clinical trials information from the perspective of systematic review and evidence-based decision making. Results The technology currently used has major shortcomings, which cause deficiencies in the transfer, traceability and availability of clinical trials information. Specifically, data available to decision makers is insufficiently structured, and consequently the decisions cannot be properly traced back to the underlying evidence. Regulatory submission, trial publication, trial registration, and systematic review produce unstructured datasets that are insufficient for supporting evidence-based decision making. Conclusions The current situation is a hindrance to policy decision makers as it prevents fully transparent decision making and the development of more advanced decision support systems. Addressing the identified deficiencies would enable more efficient, informed, and transparent evidence-based medical decision making. PMID:22947211

  9. Effect of Tesamorelin on Liver Fat and Visceral Fat in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Clinical Trial

    PubMed Central

    Stanley, Takara L.; Feldpausch, Meghan N.; Oh, Jinhee; Branch, Karen L.; Lee, Hang; Torriani, Martin; Grinspoon, Steven K.

    2015-01-01

    abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and, additionally, with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings. Trial Registration clinicaltrials.gov NCT01263717 PMID:25038357

  10. Beyond the clinic: improving child health through evidence-based community development

    PubMed Central

    2013-01-01

    Background Promoting child wellbeing necessarily goes beyond the clinic as risks to child health and development are embedded in the social and physical environmental conditions in which children live. Pediatricians play a vital role in promoting the health of children in the communities they serve and can maximize their impact by advocating for and supporting efficacious, evidence-based strategies in their communities. Methods To provide a succinct guide for community pediatric efforts to advance the wellbeing of all children and particularly disadvantaged children in a community, we conducted a theory-driven and structured narrative review to synthesize published systematic and meta-analytic reviews of policy-relevant, local-level strategies addressing potent and malleable influences on child health and development. An exhaustive list of policy-relevant, local-level strategies for improving child health was used to conduct a comprehensive search of recent (1990–2012), English language peer-reviewed published meta-analyses and systematic reviews in the 10 core databases of scientific literature. Our review of the literature encompassed six key conceptual domains of intervention foci, including distal influences of child health (i.e., income and resources, social cohesion, and physical environment) and proximal influences (i.e., family, school and peer). We examined intervention effects on four key domains of child health and development: cognitive development, social and emotional competence, psychological and behavioral wellbeing, and physical health. Results Published reviews were identified for 98 distinct policy-relevant community interventions, evaluated across 288 outcomes. We classified 46 strategies as meeting scientific criteria for efficacy by having consistent, positive outcomes from high-quality trials (e.g., tenant-based rental assistance, neighborhood watch programs, urban design and land use policies, access to quality childcare services, class

  11. The Prognosis of Allocentric and Egocentric Neglect: Evidence from Clinical Scans

    PubMed Central

    Chechlacz, Magdalena; Rotshtein, Pia; Roberts, Katherine L.; Bickerton, Wai-Ling; Lau, Johnny K. L.; Humphreys, Glyn W.

    2012-01-01

    We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms

  12. Empirically Supported Treatments in Psychotherapy: Towards an Evidence-Based or Evidence-Biased Psychology in Clinical Settings?

    PubMed Central

    Castelnuovo, Gianluca

    2010-01-01

    The field of research and practice in psychotherapy has been deeply influenced by two different approaches: the empirically supported treatments (ESTs) movement, linked with the evidence-based medicine (EBM) perspective and the “Common Factors” approach, typically connected with the “Dodo Bird Verdict”. About the first perspective, since 1998 a list of ESTs has been established in mental health field. Criterions for “well-established” and “probably efficacious” treatments have arisen. The development of these kinds of paradigms was motivated by the emergence of a “managerial” approach and related systems for remuneration also for mental health providers and for insurance companies. In this article ESTs will be presented underlining also some possible criticisms. Finally complementary approaches, that could add different evidence in the psychotherapy research in comparison with traditional EBM approach, are presented. PMID:21833197

  13. Methodology for Developing Evidence-Based Clinical Imaging Guidelines: Joint Recommendations by Korean Society of Radiology and National Evidence-Based Healthcare Collaborating Agency

    PubMed Central

    Choi, Sol Ji; Jeong, Woo Kyoung; Jo, Ae Jeong; Choi, Jin A; Kim, Min-Jeong; Lee, Min; Jung, Seung Eun; Do, Kyung Hyun; Yong, Hwan Seok; Sheen, Seungsoo

    2017-01-01

    This paper is a summary of the methodology including protocol used to develop evidence-based clinical imaging guidelines (CIGs) in Korea, led by the Korean Society of Radiology and the National Evidence-based Healthcare Collaborating Agency. This is the first protocol to reflect the process of developing diagnostic guidelines in Korea. The development protocol is largely divided into the following sections: set-up, process of adaptation, and finalization. The working group is composed of clinical imaging experts, and the developmental committee is composed of multidisciplinary experts to validate the methodology. The Korean CIGs will continue to develop based on this protocol, and these guidelines will act for decision supporting tools for clinicians as well as reduce medical radiation exposure. PMID:28096730

  14. Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations

    PubMed Central

    2012-01-01

    Clinical practice guidelines are one of the foundations of efforts to improve healthcare. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearinghouses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this second paper, we discuss issues of identifying and synthesizing evidence: deciding what type of evidence and outcomes to include in guidelines; integrating values into a guideline; incorporating economic considerations; synthesis, grading, and presentation of evidence; and moving from evidence to recommendations. PMID:22762158

  15. Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations.

    PubMed

    Woolf, Steven; Schünemann, Holger J; Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul

    2012-07-04

    Clinical practice guidelines are one of the foundations of efforts to improve healthcare. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearinghouses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this second paper, we discuss issues of identifying and synthesizing evidence: deciding what type of evidence and outcomes to include in guidelines; integrating values into a guideline; incorporating economic considerations; synthesis, grading, and presentation of evidence; and moving from evidence to recommendations.

  16. Anaerobic biodegradation of oleic and palmitic acids: evidence of mass transfer limitations caused by long chain fatty acid accumulation onto the anaerobic sludge.

    PubMed

    Pereira, M A; Pires, O C; Mota, M; Alves, M M

    2005-10-05

    Palmitic acid was the main long chain fatty acids (LCFA) that accumulated onto the anaerobic sludge when oleic acid was fed to an EGSB reactor. The conversion between oleic and palmitic acid was linked to the biological activity. When palmitic acid was fed to an EGSB reactor it represented also the main LCFA that accumulated onto the sludge. The way of palmitic acid accumulation was different in the oleic and in the palmitic acid fed reactors. When oleic acid was fed, the biomass-associated LCFA (83% as palmitic acid) were mainly adsorbed and entrapped in the sludge that became "encapsulated" by an LCFA layer. However, when palmitic acid was fed, the biomass-associated LCFA (the totality as palmitic acid) was mainly precipitated in white spots like precipitates in between the sludge, which remained "non-encapsulated." The two sludges were compared in terms of the specific methanogenic activity (SMA) in the presence of acetate, propionate, butyrate, and H(2)CO(2), before and after the mineralization of similar amounts of biomass-associated LCFA (4.6 and 5.2 g COD-LCFA/g of volatile suspended solids (VSS), for the oleic and palmitic acid fed sludge, respectively). The "non-encapsulated," sludge exhibited a considerable initial methanogenic activity on all the tested substrates, with the single exception of butyrate. However, with the "encapsulated" sludge only methane production from ethanol and H(2)/CO(2) was detected, after a lag phase of about 50 h. After mineralization of the biomass-associated LCFA, both sludges exhibited activities of similar order of magnitude in the presence of the same individual substrates and significantly higher than before. The results evidenced that LCFA accumulation onto the sludge can create a physical barrier and hinder the transfer of substrates and products, inducing a delay on the initial methane production. Whatever the mechanism, metabolic or physical, that is behind this inhibition, it is reversible, being eliminated after the

  17. Regulation of myofibrillar accumulation in chick muscle cultures - Evidence for the involvement of calcium and lysosomes in non-uniform turnover of contractile proteins

    NASA Technical Reports Server (NTRS)

    Silver, Geri; Etlinger, Joseph D.

    1985-01-01

    The effects of calcium on the synthesis and the degradation of individual myofibrillar proteins were investigated using primary chick-leg skeletal muscle cultures labeled with S-35-methionine (for protein accumulation experiments) or Ca(2+)-45 (for calcium efflux experiments). It was found that the turnover of individual contractile proteins is regulated nonuniformly by a calcium-dependent mechanism involving lysosomes. The results also indicate that contractile proteins are released from the myofibril before their breakdown to amino acids.

  18. Intentional burn injury: an evidence-based, clinical and forensic review.

    PubMed

    Greenbaum, Adam R; Donne, Jeremy; Wilson, Diana; Dunn, Kenneth W

    2004-11-01

    Burn injury can be inflicted intentionally either by one person to another whenever one has the ability to physically control the other, or it can be self-inflicted. There is scant evidential basis for much that is written about and practiced in the evaluation and care of patients that have sustained intentional burn injuries. Yet this is an area in which medical personnel must necessarily be trained in both the therapeutic and forensic aspects of a complex problem. Failure to appreciate the complexity of medical and forensic interactions may have far reaching effects. A missed diagnosis can result in inappropriate medical care, on-going abuse and future fatality. Inept management can result on the one hand, in blame levelled inappropriately placing incomparable strain on family units and innocent parties, and on the other, allow abusers to continue unchecked. This is the first review on the subject in which lawyers and doctors collaborate to produce a holistic approach to this subject. In it we describe the legal considerations that medical staff must appreciate when approaching patients who may have suffered intentional burns. We analyse the various scenarios in which intentional burning can be found and challenge the clinical dogma with much of the management of paediatric inflicted burns has become imbued. We suggest a rational and balanced approach to all intentional burn injuries-especially when children are involved. In the light of current case law in which dogmatic medical evidence has been implicated in wrongful convictions for child abuse in the UK, it is imperative that medical professionals gather evidence carefully and completely and apply it with logic and impartiality. This paper will aid clinicians who may not be experienced in dealing with burn injuries, but find themselves in the position of seeing a burn acutely, to avoid common mistakes.

  19. Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review

    PubMed Central

    Arab, Juan P; Candia, Roberto; Zapata, Rodrigo; Muñoz, Cristián; Arancibia, Juan P; Poniachik, Jaime; Soza, Alejandro; Fuster, Francisco; Brahm, Javier; Sanhueza, Edgar; Contreras, Jorge; Cuellar, M Carolina; Arrese, Marco; Riquelme, Arnoldo

    2014-01-01

    AIM: To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS: NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS: A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form of NAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION: Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events. PMID:25232252

  20. Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

    PubMed Central

    2012-01-01

    Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C) levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for consumption including spreads

  1. [Evidence-based clinical practice guidelines in oral care 3. Support for the development of clinical practice guidelines].

    PubMed

    van Dam, B A F M; Oosterkamp, B C M; den Boer, J C L; Bruers, J J M

    2015-02-01

    Support is an important factor in the implementation of clinical practice guidelines. Data from 5 studies from 1998 through 2013 offer insight into the support for clinical practice guidelines among dentists, orthodontists, dental hygienists and denturists in the Netherlands. In these, attitudes, opinions, knowledge and behaviour were seen as indicators of support. Dentists have an increasingly positive attitude towards clinical practice guidelines. The majority is aware of and uses at least 1 of the guidelines available to them and are in favour of the development of clinical practice guidelines. Orthodontists and dental hygienists have available few such guidelines, but the majority of both groups favour their development. Among denturists, who also have little experience with clinical practice guidelines, there are fewer supporters for their development. All in all, among caregivers in oral healthcare in the Netherlands, support for the use and development of clinical practice guidelines is growing.

  2. Transcatheter embolization therapy in liver cancer: an update of clinical evidences

    PubMed Central

    De Baere, Thierry; Idée, Jean-Marc; Ballet, Sébastien

    2015-01-01

    Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients’ life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol® (Lipiodol® Ultra Fluid®, Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem® (CeloNova Biosciences Inc., USA), DC-Beads® (BTG, UK) and HepaSphere® (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres® (Sirtex Medical Limited, Australia) and TheraSphere® (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key

  3. Evidence-based clinical practice guidelines for peptic ulcer disease 2015.

    PubMed

    Satoh, Kiichi; Yoshino, Junji; Akamatsu, Taiji; Itoh, Toshiyuki; Kato, Mototsugu; Kamada, Tomoari; Takagi, Atsushi; Chiba, Toshimi; Nomura, Sachiyo; Mizokami, Yuji; Murakami, Kazunari; Sakamoto, Choitsu; Hiraishi, Hideyuki; Ichinose, Masao; Uemura, Naomi; Goto, Hidemi; Joh, Takashi; Miwa, Hiroto; Sugano, Kentaro; Shimosegawa, Tooru

    2016-03-01

    The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.

  4. Elastographic characteristics of the metacarpal tendons in horses without clinical evidence of tendon injury.

    PubMed

    Lustgarten, Meghann; Redding, W Rich; Labens, Raphael; Morgan, Michel; Davis, Weston; Seiler, Gabriela S

    2014-01-01

    Tendon and ligament injuries are common causes of impaired performance in equine athletes. Gray-scale ultrasonography is the current standard method for diagnosing and monitoring these injuries, however this modality only provides morphologic information. Elastography is an ultrasound technique that allows detection and measurement of tissue strain, and may provide valuable mechanical information about equine tendon and ligament injuries. The purpose of this study was to determine the feasibility, reproducibility, and repeatability of elastography; and to describe elastographic characteristics of metacarpal tendons in sound horses. Nineteen legs for 17 clinically sound horses without evidence of musculoskeletal pathology were included. Elastographic images of the superficial and deep digital flexor tendons and the branches of the suspensory ligament (tendon of the interosseous muscle) were described quantitatively and qualitatively. There was no statistically significant difference between operators (P = 0.86) nor within operators (P = 0.93). For qualitative assessments, reproducibility (0.46) was moderate and repeatability (0.78) was good. Similar to human Achilles tendons, equine tendons were classified as predominantly hard using elastography. There was no statistically significant difference in stiffness of the flexor tendons (P = 0.96). No significant difference in stiffness was found with altered leg position during standing (P = 0.84) and while nonweight bearing (P = 0.61). The flexor tendons were softer when imaged in longitudinal versus transverse planes (P < 0.01) however, the suspensory branches were not (P = 0.67). Findings supported future clinical application of elastography as a noninvasive "stall-side" imaging modality for evaluation of the tendons and ligaments of the distal forelimb in horses.

  5. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization

    PubMed Central

    Kim, Edwin H.; Bird, J. Andrew; Kulis, Michael; Laubach, Susan; Pons, Laurent; Shreffler, Wayne; Steele, Pamela; Kamilaris, Janet; Vickery, Brian; Burks, A. Wesley

    2011-01-01

    Background There are no treatments currently available for peanut allergy. Sublingual immunotherapy is a novel approach to the treatment of peanut allergy. Objective To investigate the safety, clinical effectiveness and immunologic changes with sublingual immunotherapy in peanut-allergic children. Methods In this double-blind, placebo-controlled study, subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge. Results Eighteen children ages 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median 1710 mg vs. 85 mg, p=0.011). Mechanistic studies demonstrated a decrease in prick skin test wheal size (p=0.020) and decreased basophil responsiveness after stimulation with 10−2 mcg/ml (p=0.009) and 10−3 mcg/ml (p=0.009) of peanut. Peanut-specific IgE increased over the initial 4 months (p=0.002) then steadily decreased over the remaining 8 months (p=0.003) while peanut-specific IgG4 increased during the 12 months (p=0.014). Lastly, IL-5 levels decreased after 12 months (p=0.015). No statistically significant changes were found in IL-13 levels, the percent of T regulatory cells, or IL-10 and IFN-gamma production. Conclusion Peanut sublingual immunotherapy is able to safely induce clinical desensitization in peanut allergic children with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine if continued peanut sublingual immunotherapy is able to induce long-term immune tolerance. PMID:21281959

  6. 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

  7. 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

  8. Pancreas Islet Transplantation for Patients With Type 1 Diabetes Mellitus: A Clinical Evidence Review

    PubMed Central

    2015-01-01

    Background Type 1 diabetes mellitus is caused by the autoimmune destruction of pancreatic beta (β) cells, resulting in severe insulin deficiency. Islet transplantation is a β-cell replacement therapeutic option that aims to restore glycemic control in patients with type 1 diabetes. The objective of this study was to determine the clinical effectiveness of islet transplantation in patients with type 1 diabetes, with or without kidney disease. Methods We conducted a systematic review of the literature on islet transplantation for type 1 diabetes, including relevant health technology assessments, systematic reviews, meta-analyses, and observational studies. We used a two-step process: first, we searched for systematic reviews and health technology assessments; second, we searched primary studies to update the chosen health technology assessment. The Assessment of Multiple Systematic Reviews measurement tool was used to examine the methodological quality of the systematic reviews and health technology assessments. We assessed the quality of the body of evidence and the risk of bias according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results Our searched yielded 1,354 citations. One health technology assessment, 11 additional observational studies to update the health technology assessment, one registry report, and four guidelines were included; the observational studies examined islet transplantation alone, islet-after-kidney transplantation, and simultaneous islet-kidney transplantation. In general, low to very low quality of evidence exists for islet transplantation in patients with type 1 diabetes with difficult-to-control blood glucose levels, with or without kidney disease, for these outcomes: health-related quality of life, secondary complications of diabetes, glycemic control, and adverse events. However, high quality of evidence exists for the specific glycemic control outcome of insulin

  9. Absence of an Orphan Mitochondrial Protein, C19orf12, Causes a Distinct Clinical Subtype of Neurodegeneration with Brain Iron Accumulation

    PubMed Central

    Hartig, Monika B.; Iuso, Arcangela; Haack, Tobias; Kmiec, Tomasz; Jurkiewicz, Elzbieta; Heim, Katharina; Roeber, Sigrun; Tarabin, Victoria; Dusi, Sabrina; Krajewska-Walasek, Malgorzata; Jozwiak, Sergiusz; Hempel, Maja; Winkelmann, Juliane; Elstner, Matthias; Oexle, Konrad; Klopstock, Thomas; Mueller-Felber, Wolfgang; Gasser, Thomas; Trenkwalder, Claudia; Tiranti, Valeria; Kretzschmar, Hans; Schmitz, Gerd; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger

    2011-01-01

    The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders. PMID:21981780

  10. 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.

  11. Counseling in fetal medicine: evidence-based answers to clinical questions on morbidly adherent placenta.

    PubMed

    D'Antonio, F; Palacios-Jaraquemada, J; Lim, P S; Forlani, F; Lanzone, A; Timor-Tritsch, I; Cali, G

    2016-03-01

    Although the incidence of morbidly adherent placenta (MAP) has risen progressively in the last two decades, there remains uncertainty about the diagnosis and management of this condition. The aim of this review is to provide up-to-date and evidence-based answers to common clinical questions regarding the diagnosis and management of MAP. Different risk factors have been associated with MAP; however, previous Cesarean section and placenta previa are the most frequently associated. Ultrasound is the primary method for diagnosing MAP and has a good overall diagnostic accuracy for its detection. When considering the different ultrasound signs of MAP, color Doppler seems to provide the best diagnostic performance. Magnetic resonance imaging has the same accuracy in diagnosing MAP as does ultrasound examination; its use should be considered when a resective procedure, such as hysterectomy, is planned as it can provide detailed information about the topography of placental invasion and predict difficulties that may arise in surgery. The optimal gestational age for delivery in pregnancies with MAP is yet to be established; planning surgery between 35 and 36 weeks of gestation provides the best balance between fetal maturity and the risk of unexpected episodes of heavy bleeding, which are more likely to occur with delivery after this timepoint, especially in severe cases of MAP. The optimal surgical approach to MAP depends on multiple factors, including availability of an experienced team, specific surgical skills and hospital resources. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  12. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms.

    PubMed

    Nemeroff, Charles B; Mayberg, Helen S; Krahl, Scott E; McNamara, James; Frazer, Alan; Henry, Thomas R; George, Mark S; Charney, Dennis S; Brannan, Stephen K

    2006-07-01

    Currently available therapeutic interventions for treatment-resistant depression, including switch, combination, and augmentation strategies, are less than ideal. Observations of mood elevation during vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy suggested a role for VNS therapy in refractory major depression and prompted clinical investigation of this neurostimulation modality. The VNS Therapy System has been available for treatment of pharmacoresistant epilepsy since 1997 and was approved by the US Food and Drug Administration for treatment-resistant depression in July, 2005. The physiology of the vagus nerve, mechanics of the VNS Therapy System, and efficacy and safety in pharmacoresistant epilepsy are reviewed. Promising results of VNS therapy for treatment-resistant depression have been forthcoming from both acute and long-term studies, evidenced in part by progressive improvements in depression rating scale scores during the 1st year of treatment with maintenance of response thereafter. VNS therapy is well tolerated in patients with either pharmacoresistant epilepsy or treatment-resistant depression. As in epilepsy, the mechanisms of VNS therapy of treatment-resistant depression are incompletely understood. However, evidence from neuroimaging and other studies suggests that VNS therapy acts via innervation of the nucleus tractus solitarius, with secondary projections to limbic and cortical structures that are involved in mood regulation, including brainstem regions that contain serotonergic (raphe nucleus) and noradrenergic (locus ceruleus) perikarya that project to the forebrain. Mechanisms that mediate the beneficial effects of VNS therapy for treatment-resistant depression remain obscure. Suggestions for future research directions are described.

  13. The Role of the Cerebellum in Schizophrenia: an Update of Clinical, Cognitive, and Functional Evidences

    PubMed Central

    Picard, Hernàn; Amado, Isabelle; Mouchet-Mages, Sabine; Olié, Jean-Pierre; Krebs, Marie-Odile

    2008-01-01

    The role of the cerebellum in schizophrenia has been highlighted by Andreasen's hypothesis of “cognitive dysmetria,” which suggests a general dyscoordination of sensorimotor and mental processes. Studies in schizophrenic patients have brought observations supporting a cerebellar impairment: high prevalence of neurological soft signs, dyscoordination, abnormal posture and propioception, impaired eyeblink conditioning, impaired adaptation of the vestibular-ocular reflex or procedural learning tests, and lastly functional neuroimaging studies correlating poor cognitive performances with abnormal cerebellar activations. Despite those compelling evidences, there has been, to our knowledge, no recent review on the clinical, cognitive, and functional literature supporting the role of the cerebellum in schizophrenia. We conducted a Medline research focusing on cerebellar dysfunctions in schizophrenia. Emphasis was given to recent literature (after 1998). The picture arising from this review is heterogeneous. While in some domains, the role of the cerebellum seems clearly defined (ie, neurological soft signs, posture, or equilibrium), in other domains, the cerebellar contribution to schizophrenia seems limited or indirect (ie, cognition) if present at all (ie, affectivity). Functional models of the cerebellum are proposed as a background for interpreting these results. PMID:17562694

  14. Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

    PubMed

    Ohashi, M; Hosoda, Y; Fujishiro, Y; Tuyuki, A; Kikuchi, K; Obara, H; Kitagawa, N; Ishikawa, T

    2001-12-01

    The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

  15. Kampo formulations, chotosan, and yokukansan, for dementia therapy: existing clinical and preclinical evidence.

    PubMed

    Matsumoto, Kinzo; Zhao, Qi; Niu, Yimin; Fujiwara, Hironori; Tanaka, Ken; Sasaki-Hamada, Sachie; Oka, Jun-Ichiro

    2013-01-01

    Cognitive deficits and behavioral and psychological symptoms of dementia (BPSD) are typical features of patients with dementia such as Alzheimer's disease (AD), vascular dementia (VD), and other forms of senile dementia. Clinical evidence has demonstrated the potential usefulness of chotosan (CTS) and yokukansan (YKS), traditional herbal formulations called Kampo medicines, in the treatment of cognitive disturbance and BPSD in dementia patients, although the indications targeted by CTS and YKS in Kampo medicine differ. The availability of CTS and YKS for treating dementia patients is supported by preclinical studies using animal models of dementia that include cognitive/emotional deficits caused by aging and diabetes, dementia risk factors. These studies have led not only to the concept of a neuronal basis for the CTS- and YKS-induced amelioration of cognitive function and emotional/psychiatric symptom-related behavior in animal models, but also to a proposal that ingredient(s) of Uncariae Uncis cum Ramulus, a medicinal herb included in CTS and YKS, may play an important role in the actions of these formulae in dementia patients. Further studies are needed to clarify the active ingredients of these formulae and their target endogenous molecules implicated in the anti-dementia drug-like actions.

  16. Steroid injections in the upper extremity: experienced clinical opinion versus evidence-based practices.

    PubMed

    Kegel, Gary; Marshall, Astrid; Barron, O Alton; Catalano, Louis W; Glickel, Steven Z; Kuhn, Margaret

    2013-09-01

    A survey regarding upper-extremity steroid injection practices was distributed to all active members of the American Society for Surgery of the Hand (ASSH) and American Shoulder and Elbow Surgeons (ASES) using SurveyMonkey. Response rates for the ASSH and ASES were 26% and 24%, respectively. The potency-adjusted dose of steroid injected for common hand and wrist injections ranged from 0.375 to 133.33 mg and for shoulder injections ranged from 0.375 to 250 mg. These ranges span 356-fold and 667-fold differences, respectively. Potency-adjusted doses differed significantly between steroid types for all injections evaluated in this study. American Society for Surgery of the Hand members gave significantly smaller doses of steroid for the glenohumeral and acromioclavicular joints than ASES members. Only 9% of respondents based injection practice on a scientific reference. Sixteen percent of ASSH and 31% of ASES respondents reported no specific rationale for their steroid injection practice; 78% of ASSH and 52% of ASES respondents attributed their rationale to some kind of instruction from their mentors or colleagues. Upper-extremity surgeons demonstrate substantial variability in their practice of steroid injections, with up to a 667-fold range in steroid dose. Experienced clinical opinion is the principal rationale for these injection practices; little rationale is based on formal scientific evidence.

  17. Nostril Morphometry Evaluation before and after Cleft Lip Surgical Correction: Clinical Evidence

    PubMed Central

    Feijo, Mario Jorge Frassy; Brandão, Stella Ramos; Pereira, Rui Manoel Rodrigues; Santos, Mariana Batista de Souza; Justino da Silva, Hilton

    2014-01-01

    Introduction The purpose to this work is to review systematically the morphological changes of the nostrils of patients undergoing surgery for correction of cleft lip and identify in the literature the issues involved in the evaluation of surgical results in this population. Review of Literature A review was conducted, searching for clinical evidence from MEDLINE. The search occurred in January 2012. Selection criteria included original articles and research articles on individual subjects with cleft lip or cleft palate with unilateral nostril anthropometric measurements before and after surgical correction of cleft lip and measurements of soft tissues. There were 1,343 articles from the search descriptors and free terms. Of these, five articles were selected. Discussion Most studies in this review evaluated children in Eastern countries, using different measurement techniques but with the aid of computers, and showed improved nostril asymmetry postoperatively compared with preoperatively. Conclusion There is a reduction of the total nasal width postoperatively compared with preoperative measurements in patients with cleft lip. PMID:25992089

  18. Evidence-based interventional pain medicine according to clinical diagnoses. 18. Painful diabetic polyneuropathy.

    PubMed

    Pluijms, Wouter; Huygen, Frank; Cheng, Jianguo; Mekhail, Nagy; van Kleef, Maarten; Van Zundert, Jan; van Dongen, Robert

    2011-01-01

    In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM-induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second-line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.

  19. [Inhaled iloprost, a selective pulmonary vasodilator. Clinical evidence from its use in perioperative pulmonary hypertension cardiovascular surgery].

    PubMed

    Santos-Martínez, Luis Efren; Baranda-Tovar, Francisco Martín; Telona-Fermán, Eslí; Barragán-García, Rodolfo; Calderón-Abbo, Moisés Cutiel

    2015-01-01

    Inhaled iloprost is one of the most recent drugs from prostanoids group's in the treatment of pulmonary arterial hypertension. His place in pulmonary hypertension seen in the perioperative cardiovascular surgery has not been defined. In this review we analyze pulmonary hypertension group's susceptibles of cardiac surgery and its importance, besides the current clinical evidence from drug use in this context.

  20. Clinical Guidelines and the Translation of Texts into Care: Overcoming Professional Conflicts Concerning Evidence-based Practice.

    ERIC Educational Resources Information Center

    Davenport, Elisabeth

    2000-01-01

    Reviews problems identified in previous research on evidence-based nursing practice; discusses conflicts between medical and nursing domains; explores the provenance and status of the clinical guideline as a translation artefact or bridging mechanism based on a social studies of science approach; and presents a case study of Scottish clinical…

  1. Mercury accumulation in sediment cores from three Washington state lakes: evidence for local deposition from a coal-fired power plant.

    PubMed

    Furl, Chad V; Meredith, Callie A

    2011-01-01

    Mercury accumulation rates measured in age-dated sediment cores were compared at three Washington state lakes. Offutt Lake and Lake St. Clair are located immediately downwind (18 and 28 km, respectively) of a coal-fired power plant and Lake Sammamish is located outside of the immediate area of the plant (110 km). The sites immediately downwind of the power plant were expected to receive increased mercury deposition from particulate and reactive mercury not deposited at Lake Sammamish. Mercury accumulation in cores was corrected for variable sedimentation, background, and sediment focusing to estimate the anthropogenic contribution (Hg(A,F)). Results indicated lakes immediately downwind of the power plant contained elevated Hg(A,F) levels with respect to the reference lake. Estimated fluxes to Lake Sammamish were compared to measured values from a nearby mercury wet deposition collector to gauge the efficacy of the core deconstruction techniques. Total deposition calculated through the sediment core (20.7 μg/m²/year) fell just outside of the upper estimate (18.9 μg/m²/year) of total deposition approximated from the wet deposition collector.

  2. Publication bias: evidence of delayed publication in a cohort study of clinical research projects.

    PubMed Central

    Stern, J. M.; Simes, R. J.

    1997-01-01

    OBJECTIVES: To determine the extent to which publication is influenced by study outcome. DESIGN: A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model. SETTING: University hospital, Sydney, Australia. STUDIES: 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988. MAIN OUTCOME MEASURES: Time to publication. RESULTS: Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large. CONCLUSIONS: This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking

  3. 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

  4. Methodological quality of systematic reviews and clinical trials on women's health published in a Brazilian evidence-based health journal

    PubMed Central

    Macedo, Cristiane Rufino; Riera, Rachel; Torloni, Maria Regina

    2013-01-01

    OBJECTIVES: To assess the quality of systematic reviews and clinical trials on women's health recently published in a Brazilian evidence-based health journal. METHOD: All systematic reviews and clinical trials on women's health published in the last five years in the Brazilian Journal of Evidence-based Health were retrieved. Two independent reviewers critically assessed the methodological quality of reviews and trials using AMSTAR and the Cochrane Risk of Bias Table, respectively. RESULTS: Systematic reviews and clinical trials accounted for less than 10% of the 61 original studies on women's health published in the São Paulo Medical Journal over the last five years. All five reviews were considered to be of moderate quality; the worst domains were publication bias and the appropriate use of study quality in formulating conclusions. All three clinical trials were judged to have a high risk of bias. The participant blinding, personnel and outcome assessors and allocation concealment domains had the worst scores. CONCLUSIONS: Most of the systematic reviews and clinical trials on women's health recently published in a Brazilian evidence-based journal are of low to moderate quality. The quality of these types of studies needs improvement. PMID:23778332

  5. Centrally necrotizing breast carcinoma: a rare histological subtype, which was cause of misdiagnosis in an evident clinical local recurrence

    PubMed Central

    2012-01-01

    Centrally necrotizing carcinoma is a rare subtype of breast carcinoma, which is characterized by an extensive central necrotic zone accounting for at least 70% of the cross-sectional area of the neoplasm. This central necrotic zone, in turn, is surrounded by a narrow rim of proliferative viable tumor cells. We report an unusual clinical situation in which a patient whose evident breast mass suggested an ipsilateral local recurrence and for which numerous attempts to confirm the histological diagnosis had failed. The patient was treated with a radical mastectomy based on clinical suspicion of breast cancer recurrence after an undesirable delay. In this case, the narrow rim of viable malignant tissue had a thickness of 0.5 to 8 mm, and the centrally necrotizing carcinoma had a central zone with a predominance of fibrosis. The special features of this case led to a misdiagnosis and to an evident clinical local recurrence. PMID:22852765

  6. Clinical evidence demonstrating the utility of inorganic nitrate in cardiovascular health.

    PubMed

    Kapil, V; Weitzberg, E; Lundberg, J O; Ahluwalia, A

    2014-04-30

    The discovery of nitric oxide and its role in almost every facet of human biology opened a new avenue for treatment through manipulation of its canonical signaling and by attempts to augment endogenous nitric oxide generation through provision of substrate and co-factors to the endothelial nitric oxide synthase complex. This has been particularly so in the cardiovascular system and it is well recognized that there is reduced bioavailable nitric oxide in patients with both cardiovascular risk factors and manifest vascular disease. However, these attempts have failed to deliver the expected benefits of such an approach. Recently, an alternative pathway for nitric oxide synthesis has been elucidated that can produce authentic nitric oxide from the 1 electron reduction of inorganic nitrite. Furthermore, it has long been known that symbiotic, facultative, oral microflora can facilitate the reduction of inorganic nitrate, that is ingested in the average diet in millimolar amounts, to inorganic nitrite itself. Thus, there exists an alternative reductive pathway from nitrate, via nitrite as an intermediate, to nitric oxide that provides a novel pathway that may be amenable to therapeutic manipulation. As such, various research groups have explored the utility of manipulation of this nitrate-nitrite-nitric oxide pathway in situations in which nitric oxide is known to have a prominent role. Animal and early-phase human studies of both inorganic nitrite and nitrate supplementation have shown beneficial effects in blood pressure control, platelet function, vascular health and exercise capacity. This review considers in detail the pathways of inorganic nitrate bioactivation and the evidence of clinical utility to date on the cardiovascular system.

  7. Distribution of inorganic and organic nutrients in the South Pacific Ocean - evidence for long-term accumulation of organic matter in nitrogen-depleted waters

    NASA Astrophysics Data System (ADS)

    Raimbault, P.; Garcia, N.; Cerutti, F.

    2008-03-01

    the surface water was only 4-5 days in the upwelling, but up to 30 days in the SPG, where light isotopic δ15N signal noted in the suspended POM suggests that N2-fixation provides a dominant supply of nitrogen to phytoplankton. The most striking feature was the large accumulation of dissolved organic matter (DOM) in the SPG compared to the surrounding waters, in particular dissolved organic carbon (DOC) where concentrations were at levels rarely measured in oceanic waters (>100 μmoles l-1). Due to this large pool of DOM in the SPG photic layer, integrated values followed a converse geographical pattern to that of inorganic nutrients with a large accumulation in the centre of the SPG. Whereas suspended particulate matter in the mixed layer had a C/N ratio largely conforming to the Redfield stochiometry (C/N≍6.6), marked deviations were observed in this excess DOM (C/N≍16 to 23). The marked geographical trend suggests that a net in situ source exists, mainly due to biological processes. Thus, in spite of strong nitrate-depletion leading to low chlorophyll biomass, the closed ecosystem of the SPG can accumulate large amounts of C-rich dissolved organic matter. The implications of this finding are examined, the conclusion being that, due to weak lateral advection, the biologically produced dissolved organic carbon can be accumulated and stored in the photic layer for very long periods. In spite of the lack of seasonal vertical mixing, a significant part of new production (up to 34%), which was mainly supported by dinitrogen fixation, can be exported to deep waters by turbulent diffusion in terms of DOC. The diffusive rate estimated in the SPG (134 μmolesC m-2 d-1), was quite equivalent to the particles flux measured by sediments traps.

  8. First Evidence of Division and Accumulation of Viable but Nonculturable Pseudomonas fluorescens Cells on Surfaces Subjected to Conditions Encountered at Meat Processing Premises▿

    PubMed Central

    Peneau, Sophie; Chassaing, Danielle; Carpentier, Brigitte

    2007-01-01

    Cleaning and disinfection of open surfaces in food industry premises leave some microorganisms behind; these microorganisms build up a resident flora on the surfaces. Our goal was to explore the phenomena involved in the establishment of this biofilm. Ceramic coupons were contaminated, once only, with Pseudomonas fluorescens suspended in meat exudate incubated at 10°C. The mean adhering population after 1 day was 102 CFU·cm−2 and 103 total cells·cm−2, i.e., the total number of cells stained by DAPI (4′,6′-diamidino-2-phenylindole). The coupons were subjected daily to a cleaning product, a disinfectant, and a further soiling with exudate. The result was a striking difference between the numbers of CFU, which reached 104 CFU·cm−2, and the numbers of total cells, which reached 2 × 106 cells·cm−2 in 10 days. By using hypotheses all leading to an overestimation of the number of dead cells, we showed that the quantity of nonculturable cells (DAPI-positive cells minus CFU) observed cannot be accounted for as an accumulation of dead cells. Some nonculturable cells are therefore dividing on the surface, although cell division is unable to continue to the stage of macrocolony formation on agar. The same phenomenon was observed when only a chlorinated alkaline product was used and the number of cells capable of reducing 5-cyano-2,3-ditolyl tetrazolium chloride was close to the number of total cells, confirming that most nonculturable cells are viable but nonculturable. Furthermore, the daily shock applied to the cells does not prompt them to enter a new lag phase. Since a single application of microorganisms is sufficient to produce this accumulation of cells, it appears that the phenomenon is inevitable on open surfaces in food industry premises. PMID:17337551

  9. Vinflunine in the treatment of advanced urothelial cancer: clinical evidence and experience

    PubMed Central

    Gerullis, Holger; Wawroschek, Friedhelm; Köhne, Claus-Henning; Ecke, Thorsten Holger

    2016-01-01

    Vinflunine (VFL) has been approved in Europe for second-line treatment of metastatic and advanced urothelial cancer after failure of platin-containing therapy. Since approval, the drug has been investigated in few clinical trials. Most of the currently available reports describe experiences with VFL in a daily clinical setting. This review gives a short overview on clinical experiences and clinical trials involving VFL since the approval of this drug in 2009. PMID:28042310

  10. Trauma-induced coagulopathy--a review of the systematic reviews: is there sufficient evidence to guide clinical transfusion practice?

    PubMed

    Curry, Nicola; Stanworth, Simon; Hopewell, Sally; Dorée, Carolyn; Brohi, Karim; Hyde, Chris

    2011-07-01

    Systematic reviews are accepted as a robust and less biased means of appraising and synthesizing results from high-quality studies. This report collated and summarized all the systematic review evidence relating to the diagnosis and management of trauma-related coagulopathy and transfusion, thereby covering the widest possible body of literature. We defined 4 key clinical questions: (1) What are the best methods of predicting and diagnosing trauma-related coagulopathy? (2) Which methods of clinical management correct coagulopathy? (3) Which methods of clinical management correct bleeding? and (4) What are the outcomes of transfusion in trauma? Thirty-seven systematic reviews were identified through searches of MEDLINE (1950-July 2010), EMBASE (1980-July 2010), The Cochrane Library (Issue 7, 2010), National Guidelines Clearing House, National Library for Health Guidelines Finder, and UKBTS SRI Transfusion Evidence Library (www.transfusionevidencelibrary.com). The evidence from the systematic review literature was scanty with many gaps, and we were not able to conclusively answer any of our 4 questions. Much more needs to be understood about how coagulopathy and bleeding in trauma are altered by transfusion practices and, most importantly, whether this translates into improved survival. There is a need for randomized controlled trials to answer these questions. The approach described in this report provides a framework for incorporating new evidence.

  11. The Collaborative Assessment and Management of Suicidality (CAMS): an evolving evidence-based clinical approach to suicidal risk.

    PubMed

    Jobes, David A

    2012-12-01

    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 clinician. This process is designed to enhance the therapeutic alliance and increase treatment motivation in the suicidal patient. Central to the CAMS approach is the use of the Suicide Status Form (SSF), which is a multipurpose clinical assessment, treatment planning, tracking, and outcome tool. The original development of CAMS was largely rooted in SSF-based quantitative and qualitative assessment of suicidal risk. As this line of research progressed, CAMS emerged as a problem-focused clinical intervention that is designed to target and treat suicidal "drivers" and ultimately eliminate suicidal coping. To date, CAMS (and the clinical use of the SSF) has been supported by six published correlational studies and one randomized clinical trial (RCT). Currently, two well-powered RCTs are under way, and various new CAMS-related projects are also being pursued. The clinical and empirical evolution of CAMS-how it was developed and what are the next steps for this clinical approach-are described here.

  12. Fluids in the Palaeogene Formation of Gaoyou Sag in the Southern Part of North Jiangsu Basin, China: Evidence for Hydrocarbon Migration and Accumulation

    NASA Astrophysics Data System (ADS)

    LI, M.; Lou, Z.; Zhu, R.; Jin, A.

    2013-12-01

    Gaoyou Sag, lying in the middle of the Dongtai Depression in the North Jiangsu basin, China, has a well developed fault system and is characterised by structurally complicated oil and gas fields. Its oil-water relationship is very complicated. In the present study, we present the distribution of formation water chemistry, crude oil density, formation pressures and fluid potential in the Palaeogene formation of the Gaoyou Sag . The purpose of this article is to: (1) analyse the cause of hydrochemical diversity; (2) identify the flow pattern and evolution; and (3) understand the interplay between the flow of formation water and hydrocarbon migration and accumulation. The results showed that large variances in formation water chemistry occur in different oilfields of the Gaoyou Sag (Figure 1) due to dilution by meteoric water recharge, concentration by membrane filtration and complexity of geological structure. The low salinity (mean values from 8.53 g/L to 9.67 g/L) of the formation water and heavy crude oil density (up to 0.94g/cm3) in the Xuchuang oilfield indicate influence from meteoric water infiltration; the deep depression areas are mainly of connate origin. Geofluids in the Xuchuang, Zhenwu and Yang'an oilfields mainly flow vertically through the Zhenwu and Hanliu faults, while geofluids in the Shanian oilfield mainly migrate laterally through the reservoirs and are adjusted vertically along some cutting faults. Palaeo-hydrodynamic evolution had an affinity with the generation, migration, accumulation and preservation of hydrocarbons. In the depositional stages of the Dainan and Sanduo formations, formation water was expelled outward and upward from lacustrine mudstones of the deep depression into shallow sands of nearby oilfields, driven by compaction and overpressure. Hydrocarbon migrated with formation water and gathered in appropriate traps, forming primary reservoirs. During the Zhenwu and Sanduo movements, there were tectonic uplifts and the strata

  13. Agonist-induced production of 1,2-diacylglycerol and phosphatidic acid in intact resistance arteries. Evidence that accumulation of diacylglycerol is not a prerequisite for contraction.

    PubMed

    Ohanian, J; Ollerenshaw, J; Collins, P; Heagerty, A

    1990-05-25

    The production of total amounts of 1,2-diacylglycerol as well as those specifically derived from inositol lipid hydrolysis was studied in intact rat resistance arteries stimulated with either noradrenaline, vasopressin, or angiotensin II at 20 s when the onset of contraction would be nearing its maximum, and at 5 min during the sustained phase of contraction. Total amounts of 1,2-diacylglycerol were not altered by any agonist at 20 s, or at 5 min. However, arachidonate-containing species of 1,2-diacylglycerol were differentially influenced being increased at 5 min by noradrenaline, and decreased at 20 s and 5 min by vasopressin. Only angiotensin II produced substantial increases in this class of 1,2-diacylglycerol at both time points. In order to investigate the fate of this second messenger total and inositol lipid derived phosphatidic acids were then measured at both 20 s and 5 min. Noradrenaline induced a rise in both total and arachidonate-containing phosphatidic acid at both times as did vasopressin. Only small increases were induced by angiotensin II at 20 s. These data demonstrate that the accumulation of 1,2-diacylglycerol generated from inositol lipid breakdown is only observed with activation by angiotensin II. Other agonists produced phosphatidic acids with time and the rate of generation of these lipids is agonist-specific. Thus phosphatidic acid may play a more prominent role during the sustained phase of contraction than previously anticipated.

  14. Strontium ranelate in the treatment of knee osteoarthritis: new insights and emerging clinical evidence

    PubMed Central

    Beaudart, Charlotte; Neuprez, Audrey; Bruyère, Olivier

    2013-01-01

    Osteoarthritis is a primary cause of disability and functional incapacity. Pharmacological treatment is currently limited to symptomatic management, and in advanced stages, surgery remains the only solution. The therapeutic armamentarium for osteoarthritis remains poor in treatments with an effect on joint structure, that is, disease-modifying osteoarthritis drugs (DMOADs). Glucosamine sulfate and chondroitin sulfate are the only medications for which some conclusive evidence for a disease-modifying effect is available. Strontium ranelate is currently indicated for the prevention of fracture in severe osteoporosis. Its efficacy and safety as a DMOAD in knee osteoarthritis has recently been explored in the SEKOIA trial, a 3-year randomized, double-blind, placebo-controlled trial. Outpatients with knee osteoarthritis, Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) of 2.5–5 mm received strontium ranelate 1 g/day (n = 558) or 2 g/day (n = 566), or placebo (n = 559). This sizable population was aged 62.9 years and had a JSW of 3.50 ± 0.84 mm. Treatment with strontium ranelate led to significantly less progression of knee osteoarthritis: estimates for annual difference in joint space narrowing versus placebo were 0.14 mm [95% confidence interval (CI) 0.05–0.23 mm; p < 0.001] for 1 g/day and 0.10 mm (95% CI 0.02–0.19 mm; p = 0.018) for 2 g/day, with no difference between strontium ranelate groups. Radiological progression was less frequent with strontium ranelate (22% with 1 g/day and 26% with 2 g/day versus 33% with placebo, both p < 0.05), as was radioclinical progression (8% and 7% versus 12%, both p < 0.05). Symptoms also improved with strontium ranelate 2 g/day only in terms of total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score (p = 0.045), and its components for pain (p = 0.028) and physical function (p = 0.099). Responder analyses using a range of criteria for symptoms indicated that the effect of strontium

  15. Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use.

    PubMed

    Hammond, Elizabeth R; Shelling, Andrew N; Cree, Lynsey M

    2016-08-01

    The ability to screen embryos for aneuploidy or inherited disorders in a minimally invasive manner may represent a major advancement for the future of embryo viability assessment. Recent studies have demonstrated that both blastocoele fluid and embryo culture medium contain genetic material, which can be isolated and subjected to downstream genetic analysis. The blastocoele fluid may represent an alternative source of nuclear DNA for aneuploidy testing, although the degree to which the isolated genetic material is solely representative of the developing embryo is currently unclear. In addition to nuclear DNA, mitochondrial DNA (mtDNA) can be detected in the embryo culture medium. Currently, the origin of this nuclear and mtDNA has not been fully evaluated and there are several potential sources of contamination that may contribute to the genetic material detected in the culture medium. There is however evidence that the mtDNA content of the culture medium is related to embryo fragmentation levels and its presence is predictive of blastulation, indicating that embryo development may influence the levels of genetic material detected. If the levels of genetic material are strongly related to aspects of embryo quality, then this may be a novel biomarker of embryo viability. If the genetic material does have an embryo origin, the mechanisms by which DNA may be released into the blastocoele fluid and embryo culture medium are unknown, although apoptosis may play a role. While the presence of this genetic material is an exciting discovery, the DNA in the blastocoele fluid and embryo culture medium appears to be of low yield and integrity, which makes it challenging to study. Further research aimed at assessing the methodologies used for both isolating and analysing this genetic material, as well as tracing its origin, are needed in order to evaluate its potential for clinical use. Should such methodologies prove to be routinely successful and the DNA recovered

  16. Combining Randomized and Non-Randomized Evidence in Clinical Research: A Review of Methods and Applications

    ERIC Educational Resources Information Center

    Verde, Pablo E.; Ohmann, Christian

    2015-01-01

    Researchers may have multiple motivations for combining disparate pieces of evidence in a meta-analysis, such as generalizing experimental results or increasing the power to detect an effect that a single study is not able to detect. However, while in meta-analysis, the main question may be simple, the structure of evidence available to answer it…

  17. Argon, oxygen, and boron isotopic evidence documenting 40ArE accumulation in phengite during water-rich high-pressure subduction metasomatism of continental crust

    NASA Astrophysics Data System (ADS)

    Menold, Carrie A.; Grove, Marty; Sievers, Natalie E.; Manning, Craig E.; Yin, An; Young, Edward D.; Ziegler, Karen

    2016-07-01

    were even older, exceeding the time of eclogite formation by a factor of 1.7. In contrast, lower pressure retrograde muscovite present within the host gneiss and in discrete shear zones cutting the selvage yield 40Ar/39Ar ages that were younger than the time of HP metamorphism and consistent with regional cooling age patterns. Our observation of high 40ArE concentrations in phengite from schistose rocks infiltrated by regionally extensive fluids at HP conditions runs contrary to widely held expectations. Conventional wisdom dictates that low phengite/fluid partition coefficients for argon (Dphg/fluid Ar =10-3to 10-5) coupled with the dry, closed systems conditions that are widely reported to characterize HP metamorphism of continental crust explains why high concentrations of 40ArE partitions are able to accumulate within phengite. We alternatively propose that phengite/fluid partition coefficients for argon increase linearly with pressure to values as high as 10-2 to allow phengites to accumulate large amounts of 40ArE from aqueous fluids under HP to UHP conditions.

  18. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation

    PubMed Central

    Hunter, Jessica Ezzell; Irving, Stephanie A.; Biesecker, Leslie G.; Buchanan, Adam; Jensen, Brian; Lee, Kristy; Martin, Christa Lese; Milko, Laura; Muessig, Kristin; Niehaus, Annie D.; O'Daniel, Julianne; Piper, Margaret A.; Ramos, Erin M.; Schully, Sheri D.; Scott, Alan F.; Slavotinek, Anne; Sobreira, Nara; Strande, Natasha; Weaver, Meredith; Webber, Elizabeth M.; Williams, Marc S.; Berg, Jonathan S.; Evans, James P.; Goddard, Katrina A.B.

    2016-01-01

    Purpose: Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research. Methods: We developed a practical, standardized protocol to identify available evidence and generate qualitative summary reports of actionability for disorders and associated genes. We applied a semiquantitative metric to score actionability. Results: We generated summary reports and actionability scores for the 56 genes and associated disorders recommended by the American College of Medical Genetics and Genomics for return as secondary findings from clinical genome-scale sequencing. We also describe the challenges that arose during the development of the protocol that highlight important issues in characterizing actionability across a range of disorders. Conclusion: The ClinGen framework for actionability assessment will assist research and clinical communities in making clear, efficient, and consistent determinations of actionability based on transparent criteria to guide analysis and reporting of findings from clinical genome-scale sequencing. Genet Med 18 12, 1258–1268. PMID:27124788

  19. Evidence for early intracellular accumulation of volatile compounds during spadix development in Arum italicum L. and preliminary data on some tropical Aroids

    NASA Astrophysics Data System (ADS)

    Leguet, Aurélia; Gibernau, Marc; Shintu, Laetitia; Caldarelli, Stefano; Moja, Sandrine; Baudino, Sylvie; Caissard, Jean-Claude

    2014-08-01

    Staining and histochemistry of volatile organic compounds (VOCs) were performed at different inflorescence developmental stages on nine aroid species; one temperate, Arum italicum and eight tropical from the genera Caladium, Dieffenbachia and Philodendron. Moreover, a qualitative and quantitative analysis of VOCs constituting the scent of A. italicum, depending on the stage of development of inflorescences was also conducted. In all nine species, vesicles were observed in the conical cells of either the appendix or the stamens (thecae) and the staminodes. VOCs were localised in intracellular vesicles from the early stages of inflorescence development until their release during receptivity of gynoecium. This localisation was observed by the increase of both number and diameter of the vesicles during 1 week before receptivity. Afterwards, vesicles were fewer and smaller but rarely absent. In A. italicum, staining and gas chromatography analyses confirmed that the vesicles contained terpenes. The quantitatively most important ones were the sesquiterpenes, but monoterpenes were not negligible. Indeed, the quantities of terpenes matched the vesicles' size evolution during 1 week. Furthermore, VOCs from different biosynthetic pathways (sesquiterpenes and alkanes) were at their maximum quantity 2 days before gynoecium receptivity (sesquiterpenes and alkanes) or during receptivity (isobutylamine, monoterpenes, skatole and p-cresol). VOCs seemed to be emitted during gynoecium receptivity and/or during thermogenesis, and FADs are accumulated after thermogenesis in the spadix. These complex dynamics of the different VOCs could indicate specialisation of some VOCs and cell machinery to attract pollinators on the one hand and to repulse/protect against phytophagous organisms and pathogens after pollination on the other hand.

  20. Intracellular chloride activities in canine tracheal epithelium. Direct evidence for sodium-coupled intracellular chloride accumulation in a chloride-secreting epithelium.

    PubMed Central

    Welsh, M J

    1983-01-01

    Canine tracheal epithelium secretes Cl via an electrogenic transport process that appears to apply to a wide variety of secretory epithelia. To examine the mechanisms involved, intracellular chloride activity, acCl, was measured with Cl-selective intracellular microelectrodes. The results indicate that when the rate of secretion was minimal acCl was 37 mM; with stimulation of secretion the intracellular voltage depolarized, but acCl was not significantly altered, at 39 mM. These findings indicate that: (a) Cl is accumulated across the basolateral membrane under nonsecreting and secreting conditions at an activity 3.8 and 2.4 times, respectively, that predicted for an equilibrium distribution; (b) Cl exit across the apical membrane may be passive with an electrochemical driving force of 22 mV; and (c) stimulation of secretion enhanced the rate of Cl entry across the basolateral membrane, since Cl transport increased without a change in acCl. In the absence of Na in the extracellular fluid, acCl approached the value expected for an equilibrium distribution. This finding suggests that "uphill" entry of Cl into the cell against its electrochemical gradient is dependent upon, and energized by, the entry of Na down its gradient. Submucosal bumetanide, a loop diuretic, also decreased the rate of Cl secretion and decreased acCl, indicating an inhibition of Cl entry. These findings indicate that Cl entry into the cell is directed against its electrochemical gradient and is mediated by a Na-coupled, bumetanide-inhibitable, transport process at the basolateral membrane and that Cl may exit passively down a favorable electrochemical gradient across the apical membrane. PMID:6853719

  1. Comparative outcome studies of clinical decision support software: limitations to the practice of evidence-based system acquisition.

    PubMed

    Dhiman, Gaurav Jay; Amber, Kyle T; Goodman, Kenneth W

    2015-04-01

    Clinical decision support systems (CDSSs) assist clinicians with patient diagnosis and treatment. However, inadequate attention has been paid to the process of selecting and buying systems. The diversity of CDSSs, coupled with research obstacles, marketplace limitations, and legal impediments, has thwarted comparative outcome studies and reduced the availability of reliable information and advice for purchasers. We review these limitations and recommend several comparative studies, which were conducted in phases; studies conducted in phases and focused on limited outcomes of safety, efficacy, and implementation in varied clinical settings. Additionally, we recommend the increased availability of guidance tools to assist purchasers with evidence-based purchases. Transparency is necessary in purchasers' reporting of system defects and vendors' disclosure of marketing conflicts of interest to support methodologically sound studies. Taken together, these measures can foster the evolution of evidence-based tools that, in turn, will enable and empower system purchasers to make wise choices and improve the care of patients.

  2. Bringing evidence to practice: a team approach to teaching skills required for an informationist role in evidence-based clinical and public health practice*†

    PubMed Central

    Oliver, Kathleen Burr; Dalrymple, Prudence; Lehmann, Harold P.; McClellan, Deborah Ann; Robinson, Karen A.; Twose, Claire

    2008-01-01

    Objective: The objectives were (1) to develop an academic, graduate-level course designed for information professionals seeking to bring evidence to clinical medicine and public health practice and to address, in the course approach, the “real-world” time constraints of these domains and (2) to further specify and realize identified elements of the “informationist” concept. Setting: The course took place at the Division of Health Sciences Informatics, School of Medicine, Johns Hopkins University. Participants: A multidisciplinary faculty, selected for their expertise in the course core competencies, and three students, two post-graduate National Library of Medicine (NLM) informationist fellows and one NLM second-year associate, participated in the research. Intervention: A 1.5-credit, graduate-level course, “Informationist Seminar: Bringing the Evidence to Practice,” was offered in October to December 2006. In this team-taught course, a series of lectures by course faculty and panel discussions involving outside experts were combined with in-class discussion, homework exercises, and a major project that involved choosing and answering, in both oral and written form, a real-world question based on a case scenario in clinical or public health practice. Conclusion: This course represents an approach that could be replicated in other academic health centers with similar pools of expertise. Ongoing journal clubs that reiterate the question-and-answer process with new questions derived from clinical and public health practice and incorporate peer review and faculty mentoring would reinforce the skills acquired in the seminar. PMID:18219381

  3. Clinical and personality traits in emotional disorders: Evidence of a common framework.

    PubMed

    Mahaffey, Brittain L; Watson, David; Clark, Lee Anna; Kotov, Roman

    2016-08-01

    Certain clinical traits (e.g., ruminative response style, self-criticism, perfectionism, anxiety sensitivity, fear of negative evaluation, and thought suppression) increase the risk for and chronicity of emotional disorders. Similar to traditional personality traits, they are considered dispositional and typically show high temporal stability. Because the personality and clinical-traits literatures evolved largely independently, connections between them are not fully understood. We sought to map the interface between a widely studied set of clinical and personality traits. Two samples (N = 385 undergraduates; N = 188 psychiatric outpatients) completed measures of personality traits, clinical traits, and an interview-based assessment of emotional-disorder symptoms. First, the joint factor structure of these traits was examined in each sample. Second, structural equation modeling was used to clarify the effects of clinical traits in the prediction of clinical symptoms beyond negative temperament. Third, the incremental validity of clinical traits beyond a more comprehensive set of higher-order and lower-order personality traits was examined using hierarchical regression. Clinical and personality traits were highly correlated and jointly defined a 3-factor structure-Negative Temperament, Positive Temperament, and Disinhibition-in both samples, with all clinical traits loading on the Negative Temperament factor. Clinical traits showed modest but significant incremental validity in explaining symptoms after accounting for personality traits. These data indicate that clinical traits relevant to emotional disorders fit well within the traditional personality framework and offer some unique contributions to the prediction of psychopathology, but it is important to distinguish their effects from negative temperament/neuroticism. (PsycINFO Database Record

  4. Evidence-based dentistry: Part II. Searching for answers to clinical questions: how to use MEDLINE.

    PubMed

    Sutherland, S E

    2001-05-01

    The ability to conduct efficient literature searches is fundamental to the practice of evidence-based dentistry. In the second part of this series on evidence-based dentistry, strategic literature search techniques are discussed. MEDLINE, because of its breadth, depth and continuous maintenance by the U.S. National Library of Medicine (NLM), is the best source of evidence for health care. Although there are many gateways to MEDLINE, this paper highlights the user-friendly versions of MEDLINE offered free on the Internet by the NLM. The use of well-established search tactics and the unique features of the NLM sites facilitate rapid, effective literature searches.

  5. Enhancing a Culture of Inquiry: The Role of a Clinical Nurse Specialist in Supporting the Adoption of Evidence.

    PubMed

    Patterson, Amy E; Mason, Tina M; Duncan, Pamela

    2017-03-01

    This article describes a Magnet®-designated, national cancer institute comprehensive cancer center's quest to restructure the organization's evidence-based practice (EBP)/performance improvement (PI) framework leveraging the role of the clinical nurse specialist (CNS) as a coach to support staff nurses in EBP/PI initiatives. The support of the CNS is essential in developing effective projects, minimizing barriers, and maintaining a level of engagement in the EBP process from problem identification through dissemination and sustainment of practice changes.

  6. 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.

  7. Evaluating Evidence-Informed Clinical Reasoning Proficiency in Oral Practical Examinations

    ERIC Educational Resources Information Center

    Geisler, Paul R.; Hummel, Chris; Piebes, Sarah

    2014-01-01

    Clinical reasoning is the specific cognitive process used by health care practitioners to formulate accurate diagnoses for complex patient problems and to set up and carry out effective care. Athletic training students and practitioners need to develop and display effective clinical reasoning skills in the assessment of injury and illness as a…

  8. Astragalus in the Prevention of Upper Respiratory Tract Infection in Children with Nephrotic Syndrome: Evidence-Based Clinical Practice

    PubMed Central

    Zou, Chuan; Su, Guobin; Wu, Yuchi; Lu, Fuhua; Mao, Wei; Liu, Xusheng

    2013-01-01

    Aims. To explore whether Astragalus or its formulations could prevent upper respiratory infection in children with nephrotic syndrome and how best to use it. Methods. We transformed a common clinical question in practice to an answerable question according to the PICO principle. Databases, including the Cochrane Library (Issue 5, 2012), PUBMED (1966–2012.8), CBM (1978–2012.8), VIP (1989–2012.8), and CNKI (1979–2012.8), were searched to identify Cochrane systematic reviews and clinical trials. Then, the quality of and recommendations from the clinical evidence were evaluated using the GRADEpro software. Results. The search yielded 537 papers. Only two studies with high validity were included for synthesis calculations. The results showed that Astragalus granules could effectively reduce URTI in children with nephrotic syndrome compared with prednisone treatment alone (23.9% versus 42.9%; RR = 0.56 and 95% CI = 0.33–0.93). The dose of Astragalus granules was 2.25 gram (equivalent to 15 gram crude Astragalus) twice per day, at least for 3–6 months. The level of evidence quality was low, but we still recommended the evidence to the patient according to GRADEpro with the opinion of the expert. Followup showed the incidence of URTI in this child decreased significantly. Conclusions. Astragalus granules may reduce the incidence of URTI in children with nephrotic syndrome. PMID:23662131

  9. The first center for evidence-based medicine in Lithuania: an opportunity to change culture and improve clinical practice.

    PubMed

    Beinortas, Tumas; Bauza, Karolis; Howick, Jeremy; Nunan, David; Mahtani, Kamal Ram

    2015-05-01

    In post-Soviet countries, where medical practice largely relies on experience alone, the incorporation of the best research evidence in clinical practice is limited. In order to promote the awareness and utilization of evidence-based medicine (EBM) among Lithuanian doctors, we organized EBM conferences in each of the two Lithuanian medical schools. More than 500 medical professionals and students attended the conferences in Vilnius (2013) and Kaunas (2014) demonstrating that there is a high demand for formal EBM teaching. Building on the success of these seminal conferences, and to start addressing the lack of EBM practice in the country, the first Lithuanian Centre for Evidence-Based Medicine was established at Vilnius University Medical Faculty in 2014. The Centre will focus on the implementation of EBM teaching in medical school curriculum, formulating management guidelines, writing systematic reviews and supporting Lithuanian authors in doing so.

  10. Holmium laser enucleation of the prostate: a review of the clinical trial evidence

    PubMed Central

    2014-01-01

    Transurethral resection of the prostate (TURP) has remained the procedure of choice for the surgical treatment of bladder outflow obstruction for almost five decades, but holmium laser enucleation of the prostate (HoLEP) is now emerging as a challenger as the gold standard procedure. This review summarizes the evidence base for HoLEP, with particular reference to randomized, controlled (level 1) evidence. PMID:24688602

  11. The efficacy of negative pressure wound therapy in the management of lower extremity trauma: review of clinical evidence.

    PubMed

    Kanakaris, N K; Thanasas, C; Keramaris, N; Kontakis, G; Granick, Mark S; Giannoudis, P V

    2007-12-01

    A large number of aids have been conceived and introduced into clinical practice (nutritional supplements, local dressings, technical innovations) aimed at facilitating and optimising wound healing in both acute and chronic wound settings. Among these advances, negative pressure wound therapy (NPWT) has been introduced during the last 30 years, and has been analysed in over 400 manuscripts of the English, Russian and German literature. Until very recently, vacuum assisted closure (VAC) (KCI, TX, USA) has been the only readily available commercial device that provides localised negative pressure to the wound and is the predominant agent used to deliver NPWT featured in this review. We conducted a comprehensive review of the existing clinical evidence of the English literature on the applications of NPWT in the acute setting of trauma and burns of the lower extremity. Overall, 16 clinical studies have been evaluated and scrutinised as to the safety and the efficacy of this adjunct therapy in the specific environment of trauma. Effectiveness was comparable to the standard dressing and wound coverage methods. The existing clinical evidence justifies its application in lower limb injuries associated with soft tissue trauma.

  12. Body checking in non-clinical women: experimental evidence of a specific impact on fear of uncontrollable weight gain.

    PubMed

    Bailey, Natalie; Waller, Glenn

    2017-01-20

    Body checking is used widely among clinical and non-clinical individuals. It is suggested to be a safety behavior, reducing anxiety initially but potentially enhancing eating and shape concerns in the longer term. However, there is little causal evidence of those negative effects. This experimental study tests the potential negative impact of body checking. Fifty non-clinical women took part in a study of the effects of body checking in naturalistic settings. Each checked their wrist size every 15 minutes for eight hours on one day, then did not check the next day (order randomized). The impact on eating cognitions and body dissatisfaction was measured at the end of each day, and levels of change in those characteristics were also associated with eating pathology levels. Body checking did not result in more negative general eating attitudes or body dissatisfaction, but did result in a significant increase in a specific cognition that is hypothesised to be relevant to eating pathology - the fear of uncontrollable weight gain following eating. This impact was greater among those women with more negative existing eating attitudes. These findings add to the small experimental evidence base, demonstrating negative causal links between body checking and eating pathology. The findings need to be extended to clinical groups, but support the use of existing cognitive-behavioral methods to reduce body checking behavior.

  13. Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

    PubMed

    Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

    2011-02-01

    Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution

  14. Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease in an Asian Memory ClinicEvidence for a Clinical Spectrum

    PubMed Central

    Chan, M.; Tay, L.; Chong, M.S.

    2011-01-01

    Objectives To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits. Methods Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton's scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed. Results ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively). Conclusions Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development. PMID:22163238

  15. Evidence-based risk recommendations for best practices in the training of qualified exercise professionals working with clinical populations.

    PubMed

    Warburton, Darren E R; Bredin, Shannon S D; Charlesworth, Sarah A; Foulds, Heather J A; McKenzie, Don C; Shephard, Roy J

    2011-07-01

    This systematic review examines critically "best practices" in the training of qualified exercise professionals. Particular attention is given to the core competencies and educational requirements needed for working with clinical populations. Relevant information was obtained by a systematic search of 6 electronic databases, cross-referencing, and through the authors' knowledge of the area. The level and grade of the available evidence was established. A total of 52 articles relating to best practices and (or) core competencies in clinical exercise physiology met our eligibility criteria. Overall, current literature supports the need for qualified exercise professionals to possess advanced certification and education in the exercise sciences, particularly when dealing with "at-risk" populations. Current literature also substantiates the safety and effectiveness of exercise physiologist supervised stress testing and training in clinical populations.

  16. [Clinical orientation of post-marketing Chinese patent drugs: an evidence-based practice].

    PubMed

    Shang, Hong-Cai; Zhang, Bo-Li; Li, You-Ping

    2008-09-01

    Unclear clinical orientation in practice has become one of the common problems with the effective application of famous and excellent Chinese herbal drugs, consequently restricting their development. The authors suggest that there are three aspects to be considered in dealing with this problem. Clinical evaluation and orientation of the famous and excellent Chinese herbal drugs is an important task, and it is also a requirement for the internationalization of traditional Chinese medicine. Literature evaluation-pharmacology research-clinical expertise analysis method will establish a theoretical basis and method for post-marketing development of famous and excellent Chinese patent drugs.

  17. Evidence That a Psychopathology Interactome Has Diagnostic Value, Predicting Clinical Needs: An Experience Sampling Study

    PubMed Central

    van Os, Jim; Lataster, Tineke; Delespaul, Philippe; Wichers, Marieke; Myin-Germeys, Inez

    2014-01-01

    Background For the purpose of diagnosis, psychopathology can be represented as categories of mental disorder, symptom dimensions or symptom networks. Also, psychopathology can be assessed at different levels of temporal resolution (monthly episodes, daily fluctuating symptoms, momentary fluctuating mental states). We tested the diagnostic value, in terms of prediction of treatment needs, of the combination of symptom networks and momentary assessment level. Method Fifty-seven patients with a psychotic disorder participated in an ESM study, capturing psychotic experiences, emotions and circumstances at 10 semi-random moments in the flow of daily life over a period of 6 days. Symptoms were assessed by interview with the Positive and Negative Syndrome Scale (PANSS); treatment needs were assessed using the Camberwell Assessment of Need (CAN). Results Psychotic symptoms assessed with the PANSS (Clinical Psychotic Symptoms) were strongly associated with psychotic experiences assessed with ESM (Momentary Psychotic Experiences). However, the degree to which Momentary Psychotic Experiences manifested as Clinical Psychotic Symptoms was determined by level of momentary negative affect (higher levels increasing probability of Momentary Psychotic Experiences manifesting as Clinical Psychotic Symptoms), momentary positive affect (higher levels decreasing probability of Clinical Psychotic Symptoms), greater persistence of Momentary Psychotic Experiences (persistence predicting increased probability of Clinical Psychotic Symptoms) and momentary environmental stress associated with events and activities (higher levels increasing probability of Clinical Psychotic Symptoms). Similarly, the degree to which momentary visual or auditory hallucinations manifested as Clinical Psychotic Symptoms was strongly contingent on the level of accompanying momentary paranoid delusional ideation. Momentary Psychotic Experiences were associated with CAN unmet treatment needs, over and above PANSS

  18. Applying psychological theory to evidence-based clinical practice: identifying factors predictive of taking intra-oral radiographs.

    PubMed

    Bonetti, Debbie; Pitts, Nigel B; Eccles, Martin; Grimshaw, Jeremy; Johnston, Marie; Steen, Nick; Glidewell, Liz; Thomas, Ruth; Maclennan, Graeme; Clarkson, Jan E; Walker, Anne

    2006-10-01

    This study applies psychological theory to the implementation of evidence-based clinical practice. The first objective was to see if variables from psychological frameworks (developed to understand, predict and influence behaviour) could predict an evidence-based clinical behaviour. The second objective was to develop a scientific rationale to design or choose an implementation intervention. Variables from the Theory of Planned Behaviour, Social Cognitive Theory, Self-Regulation Model, Operant Conditioning, Implementation Intentions and the Precaution Adoption Process were measured, with data collection by postal survey. The primary outcome was the number of intra-oral radiographs taken per course of treatment collected from a central fee claims database. Participants were 214 Scottish General Dental Practitioners. At the theory level, the Theory of Planned Behaviour explained 13% variance in the number of radiographs taken, Social Cognitive Theory explained 7%, Operant Conditioning explained 8%, Implementation Intentions explained 11%. Self-Regulation and Stage Theory did not predict significant variance in radiographs taken. Perceived behavioural control, action planning and risk perception explained 16% of the variance in number of radiographs taken. Knowledge did not predict the number of radiographs taken. The results suggest an intervention targeting predictive psychological variables could increase the implementation of this evidence-based practice, while influencing knowledge is unlikely to do so. Measures which predicted number of radiographs taken also predicted intention to take radiographs, and intention accounted for significant variance in behaviour (adjusted R(2)=5%: F(1,166)=10.28, p<.01), suggesting intention may be a possible proxy for behavioural data when testing an intervention prior to a service-level trial. Since psychological frameworks incorporate methodologies to measure and change component variables, taking a theory-based approach

  19. 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

  20. Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies.

    PubMed

    Holmström, Gerd; van Wijngaarden, Peter; Coster, Douglas J; Williams, Keryn A

    2007-12-01

    Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including the influences of sex, ethnicity, and ocular pigmentation. The role of polymorphisms is explored in the genes for vascular endothelial growth factor and insulin-like growth factor-1, and of mutations in the Norrie disease gene. Insights into the genetic basis of retinopathy of prematurity provided by the animal model of oxygen induced retinopathy are examined. Evidence for a genetic component for susceptibility to retinopathy of prematurity is strong, although the molecular identity of the gene or genes involved remains uncertain.

  1. Histological Validity and Clinical Evidence for Use of Fractional Lasers for Acne Scars

    PubMed Central

    Sardana, Kabir; Garg, Vijay K; Arora, Pooja; Khurana, Nita

    2012-01-01

    Though fractional lasers are widely used for acne scars, very little clinical or histological data based on the objective clinical assessment or the depth of penetration of lasers on in vivo facial tissue are available. The depth probably is the most important aspect that predicts the improvement in acne scars but the studies on histology have little uniformity in terms of substrate (tissue) used, processing and stains used. The variability of the laser setting (dose, pulses and density) makes comparison of the studies difficult. It is easier to compare the end results, histological depth and clinical results. We analysed all the published clinical and histological studies on fractional lasers in acne scars and analysed the data, both clinical and histological, by statistical software to decipher their significance. On statistical analysis, the depth was found to be variable with the 1550-nm lasers achieving a depth of 679 μm versus 10,600 nm (895 μm) and 2940 nm (837 μm) lasers. The mean depth of penetration (in μm) in relation to the energy used, in millijoules (mj), varies depending on the laser studied. This was statistically found to be 12.9–28.5 for Er:glass, 3–54.38 for Er:YAG and 6.28–53.66 for CO2. The subjective clinical improvement was a modest 46%. The lack of objective evaluation of clinical improvement and scar-specific assessment with the lack of appropriate in vivo studies is a case for combining conventional modalities like subcision, punch excision and needling with fractional lasers to achieve optimal results. PMID:23060702

  2. Understanding the Common Elements of Evidence-Based Practice: Misconceptions and Clinical Examples

    ERIC Educational Resources Information Center

    Chorpita, Bruce F.; Becker, Kimberly D.; Daleiden, Eric L.

    2007-01-01

    In this article, the authors proposed a distillation and matching model (DMM) that describes how evidence-based treatment operations can be conceptualized at a lower order level of analysis than simply by their manuals. Also referred to as the "common elements" approach, this model demonstrates the feasibility of coding and identifying the…

  3. From Science to Practice: The Flexible Use of Evidence-Based Treatments in Clinical Settings

    ERIC Educational Resources Information Center

    Nock, Matthew K.; Goldman, Jennifer L.; Wang, Yanping; Albano, Anne Marie

    2004-01-01

    Psychosocial treatment options are nearly as broad as the behavioral problems that they address. With literally hundreds of treatment approaches available, how should clinicians select the most appropriate and effective intervention? One way is to consider using only those treatments with evidence of therapeutic efficacy. Indeed, funding agencies…

  4. Evidence Based Clinical Assessment of Child and Adolescent Social Phobia: A Critical Review of Rating Scales

    ERIC Educational Resources Information Center

    Tulbure, Bogdan T.; Szentagotai, Aurora; Dobrean, Anca; David, Daniel

    2012-01-01

    Investigating the empirical support of various assessment instruments, the evidence based assessment approach expands the scientific basis of psychotherapy. Starting from Hunsley and Mash's evaluative framework, we critically reviewed the rating scales designed to measure social anxiety or phobia in youth. Thirteen of the most researched social…

  5. Modafinil: a useful medication for cocaine addiction? Review of the evidence from neuropharmacological, experimental and clinical studies.

    PubMed

    Martínez-Raga, Jose; Knecht, Carlos; Cepeda, Sonsoles

    2008-06-01

    Cocaine addiction is a chronic relapsing disorder associated with severe medical and psychosocial complications. However, there are no approved medications for cocaine dependent individuals. Modafinil, a medication that differs chemically and pharmacologically from other central nervous system stimulants, has been suggested to be potentially useful for this complex disorder. The present paper aims to critically review the published evidence from laboratory and clinical studies on modafinil for cocaine addiction, including discussion of its pharmacological characteristics and how it may relate with cocaine neurobiology. Whilst its exact mechanism of action remains to be elucidated, different neurotransmitter systems have been implicated, including modulation on dopamine, glutamate/GABA, noradrenaline and the hypocretin/orexin system, but it is possible that modafinil acts by a synergistic combination of mechanisms. With a favourable pharmacokinetic profile, it appears to have a low abuse potential. Laboratory and clinical studies provide consistent, albeit preliminary, evidence of the potential usefulness of modafinil for cocaine dependent patients. Not only there is no evidence of pharmacokinetic interactions between modafinil and cocaine, but in addition cocaine induced euphoria and cardiovascular effects appear to be attenuated by modafinil. Furthermore, modafinil has been shown to decrease cocaine self-administration. In addition, modafinil treated patient are more likely to achieve protracted abstinence than placebo treated patients. However, further research is needed to confirm these findings.

  6. 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

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

    PubMed

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

    2017-02-01

    [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.

  8. Is Early Clinical Evidence of Autonomic Shift Predictive of Infection Following Aneurysmal Subarachnoid Hemorrhage?

    PubMed Central

    Fletcher, Jeffrey J.; Rajajee, Venkatakrishna; Wilson, Thomas J.; Zahuranec, Darin B.

    2014-01-01

    Background Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression following stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal SAH (aSAH). Methods Data were obtained from a single center cohort study of aSAH patients admitted January 1, 2007 through April 1, 2012. AS was defined as at least one early (<72 hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates. Results A total 167 patients were included in the analysis (mean age 56, 27% male). AS was seen in 66/167 (40%; 95% CI, 32%–47%), and infection was seen in 80/167 (48%; 95% CI, 40%–55%). AS was associated with subsequent infection on unadjusted analysis (OR=2.11; 95% CI, 1.12–3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, 0.67–2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection following aSAH. Conclusions We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding. PMID:24189451

  9. Statistical Use in Clinical Studies: Is There Evidence of a Methodological Shift?

    PubMed Central

    Yi, Dali; Ma, Dihui; Li, Gaoming; Zhou, Liang; Xiao, Qin; Zhang, Yanqi; Liu, Xiaoyu; Chen, Hongru; Pettigrew, Julia Christine; Yi, Dong; Liu, Ling; Wu, Yazhou

    2015-01-01

    Background Several studies indicate that the statistical education model and level in medical training fails to meet the demands of clinicians, especially when they want to understand published clinical research. We investigated how study designs and statistical methods in clinical studies have changed in the last twenty years, and we identified the current trends in study designs and statistical methods in clinical studies. Methods We reviewed 838 eligible clinical study articles that were published in 1990, 2000, and 2010 in four journals New England Journal of Medicine, Lancet, Journal of the American Medical Association and Nature Medicine. The study types, study designs, sample designs, data quality controls, statistical methods and statistical software were examined. Results Substantial changes occurred in the past twenty years. The majority of the studies focused on drug trials (61.6%, n = 516). In 1990, 2000, and 2010, there was an incremental increase in RCT studies (74.4%, 82.8%, and 84.0%, respectively, p = 0.013). Over time, there was increased attention on the details of selecting a sample and controlling bias, and there was a higher frequency of utilizing complex statistical methods. In 2010, the most common statistical methods were confidence interval for superiority and non-inferiority comparison (41.6%), survival analysis (28.5%), correction analysis for covariates (18.8%) and Logistic regression (15.3%). Conclusions These findings indicate that statistical measures in clinical studies are continuously developing and that the credibility of clinical study results is increasing. These findings provide information for future changes in statistical training in medical education. PMID:26448046

  10. Dopamine blockade and clinical response: Evidence for two biological subgroups of schizophrenia

    SciTech Connect

    Wolkin, A.; Barouche, F.; Wolf, A.P.; Rotrosen, J.; Fowler, J.S.; Shiue, C.Y.; Cooper, T.B.; Brodie, J.D. )

    1989-07-01

    Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using ({sup 18}F)N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of ({sup 18}F)N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.

  11. Disseminated Coccidioidomycosis with Clinically Evident Splenomegaly in an Immunocompetent Host, First Case Reported in the literature

    PubMed Central

    Bird, Garrett R.; Libke, Robert D.; Billelo, John F.; Parks, Nancy A.; Pollard, John S.

    2009-01-01

    Coccidioidomycosis is a dimorphic fungus endemic to the southwestern United States, Central and South America. We report a case of a previously healthy person who presented with respiratory failure and disseminated Coccidioidomycosis who eventually had a fatal outcome. Coccidioidomycosis, or “Valley Fever” has been called the “great imitator” (1) as it can have a wide variety of clinical presentations. This case is unique as it represents the first described case of an immunocompetent host with rapidly progressing, disseminated coccidioidomycosis with clinically apparent splenomegaly and hepatomegaly. PMID:21264046

  12. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence

    PubMed Central

    2012-01-01

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness. PMID:22834465

  13. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence.

    PubMed

    Dimitriou, Rozalia; Mataliotakis, George I; Calori, Giorgio Maria; Giannoudis, Peter V

    2012-07-26

    Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a single-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.

  14. Developing Memory Clinics in Primary Care: An Evidence-Based Interprofessional Program of Continuing Professional Development

    ERIC Educational Resources Information Center

    Lee, Linda; Weston, W. Wayne; Hillier, Loretta M.

    2013-01-01

    Introduction: Primary care is challenged to meet the needs of patients with dementia. A training program was developed to increase capacity for dementia care through the development of Family Health Team (FHT)-based interprofessional memory clinics. The interprofessional training program consisted of a 2-day workshop, 1-day observership, and 2-day…

  15. Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders.

    PubMed

    Yamasue, Hidenori

    2016-02-01

    Oxytocin is a potential therapeutic for the core symptoms of autism spectrum disorder (ASD), which is currently untreatable with pharmacotherapy. Previous clinical trials of a single dose of oxytocin have consistently reported significantly positive effects on various experimental measures associated with the core symptoms of ASD. These studies used various experimental measures as surrogate endpoints of the trials. However, to date, randomized clinical trials of continual administration of oxytocin have failed to reveal significant positive effects on clinically meaningful endpoints, such as how those with ASD interact during interpersonal interactions. This article reviews both the negative and positive effects of oxytocin on the core symptoms of ASD and their surrogate markers. Some unresolved and critical issues on the development of oxytocin as a new therapeutic have been extracted: optimization of dose, duration of oxytocin treatment, and the development of objective and reliable measurements of clinically meaningful endpoints for the core symptoms of ASD. Furthermore, optimization to the intranasal delivery system and careful consideration of how individuals respond differently to treatments should be addressed in future studies.

  16. Cognitive and affective components of Theory of Mind in preschoolers with oppositional defiance disorder: Clinical evidence.

    PubMed

    de la Osa, Nuria; Granero, Roser; Domenech, Josep Maria; Shamay-Tsoory, Simone; Ezpeleta, Lourdes

    2016-07-30

    The goal of the study was to examine the affective-cognitive components of Theory of Mind (ToM), in a community sample of 538 preschoolers, and more specifically in a subsample of 40 children diagnosed with ODD. The relationship between affective and cognitive ToM and some ODD clinical characteristics was examined. Children were assessed with structured diagnostic interviews and dimensional measures of psychopathology, impairment and unemotional traits. A measure based on eye-gaze was used to assess ToM. Mixed analysis of variance compared the mean cognitive versus affective scale scores and the between-subjects factor ODD. The association between ToM-scores and clinical measures was assessed through correlation models. Execution and reaction time to emotional and cognitive components of ToM tasks are different at age 5 in normally developing children. Oppositional Defiant children had slower response time when performing the affective mentalizing condition than children without the disorder. The correlation matrix between ToM-scores and clinical measures showed specific associations depending on the impaired ToM aspect and the psychological domain. Results may have clinical implications for the prevention and management of ODD.

  17. Evidence for the Criterion Validity and Clinical Utility of the Pathological Narcissism Inventory

    ERIC Educational Resources Information Center

    Thomas, Katherine M.; Wright, Aidan G. C.; Lukowitsky, Mark R.; Donnellan, M. Brent; Hopwood, Christopher J.

    2012-01-01

    In this study, the authors evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (N = 299 and 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic…

  18. Deconstructing Oppositional Defiant Disorder: Clinic-Based Evidence for an Anger/Irritability Phenotype

    ERIC Educational Resources Information Center

    Drabick, Deborah A. G.; Gadow, Kenneth D.

    2012-01-01

    Objective: To examine risk factors and co-occurring symptoms associated with mother-reported versus teacher-reported anger/irritability symptoms (AIS) of oppositional defiant disorder (ODD) in a clinic-based sample of 1,160 youth aged 6 through 18 years. Method: Participants completed a background history questionnaire (mothers), school…

  19. Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence

    PubMed Central

    Troiani, Teresa; Napolitano, Stefania; Della Corte, Carminia Maria; Martini, Giulia; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Fortunato

    2016-01-01

    Epidermal growth factor receptor (EGFR) plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). In the past 15 years, several EGFR antagonists have been approved for the treatment of NSCLC and metastatic CRC (mCRC). To optimise the use of anti-EGFR agents in clinical practice, various clinical and molecular biomarkers have been investigated, thus moving their indication from unselected to selected populations. Nowadays, anti-EGFR drugs represent a gold-standard therapy for metastatic NSCLC harbouring EGFR activating mutation and for RAS wild-type mCRC. Their clinical efficacy is limited by the presence of intrinsic resistance or the onset of acquired resistance. In this review, we provide an overview of the antitumour activity of EGFR inhibitors in NSCLC and CRC and of mechanisms of resistance, focusing on the development of a personalised approach through 15 years of preclinical and clinical research. PMID:27843640

  20. Building a Bridge or Digging a Pipeline? Clinical Data Mining in Evidence-Informed Knowledge Building

    ERIC Educational Resources Information Center

    Epstein, Irwin

    2015-01-01

    Challenging the "bridge metaphor" theme of this conference, this article contends that current practice-research integration strategies are more like research-to-practice "pipelines." The purpose of this article is to demonstrate the potential of clinical data-mining studies conducted by practitioners, practitioner-oriented PhD…

  1. Drugs for chronic pain in children: A commentary on clinical practice and the absence of evidence

    PubMed Central

    Grégoire, Marie-Claude; Finley, G Allen

    2013-01-01

    Pediatric chronic pain is widespread, under-recognized and undertreated. Best management usually involves a multimodal approach coordinated by a multidisciplinary team. The present commentary specifically discusses common pharmacological approaches to chronic pain in children, identifies gaps in knowledge and suggests several research directions that would benefit future clinical care. PMID:23457686

  2. Evidence-Based Decision about Test Scoring Rules in Clinical Anatomy Multiple-Choice Examinations

    ERIC Educational Resources Information Center

    Severo, Milton; Gaio, A. Rita; Povo, Ana; Silva-Pereira, Fernanda; Ferreira, Maria Amélia

    2015-01-01

    In theory the formula scoring methods increase the reliability of multiple-choice tests in comparison with number-right scoring. This study aimed to evaluate the impact of the formula scoring method in clinical anatomy multiple-choice examinations, and to compare it with that from the number-right scoring method, hoping to achieve an…

  3. Verb Morphology as Clinical Marker of Specific Language Impairment: Evidence from First and Second Language Learners

    ERIC Educational Resources Information Center

    Verhoeven, Ludo; Steenge, Judit; van Balkom, Hans

    2011-01-01

    The goal of this study was to search for verb morphology characteristics as possible clinical markers of SLI in Dutch as a first and second language. We also wanted to find out to what extent bilingual children with SLI are additionally disadvantaged in comparison to monolingual children with SLI, on the one hand, and to typically developing…

  4. Closing the Gap between Research Evidence and Clinical Practice: Jordanian Nurses' Perceived Barriers to Research Utilisation

    ERIC Educational Resources Information Center

    Al Khalaileh, Murad; Al Qadire, Mohammad; Musa, Ahmad S.; Al-Khawaldeh, Omar A.; Al Qudah, Hani; Alhabahbeh, Atalla

    2016-01-01

    Background: The nursing profession is a combination of theory and practical skill, and nurses are required to generate and develop knowledge through implementing research into clinical practice. Considerable number of barriers could hind implementing research findings into practice. Barriers to research utilisation are not identified in the…

  5. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.

    PubMed

    Badesch, David B; Abman, Steve H; Ahearn, Gregory S; Barst, Robyn J; McCrory, Douglas C; Simonneau, Gerald; McLaughlin, Vallerie V

    2004-07-01

    Pulmonary arterial hypertension (PAH) is often difficult to diagnose and challenging to treat. Untreated, it is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. The past decade has seen remarkable improvements in therapy, driven largely by the conduct of randomized controlled trials. Still, the selection of most appropriate therapy is complex, and requires familiarity with the disease process, evidence from treatment trials, complicated drug delivery systems, dosing regimens, side effects, and complications. This chapter will provide evidence-based treatment recommendations for physicians involved in the care of these complex patients. Due to the complexity of the diagnostic evaluation required, and the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center.

  6. Intracranial pressure monitoring for traumatic brain injury: available evidence and clinical implications.

    PubMed

    Stocchetti, N; Longhi, L; Zanier, E R

    2008-05-01

    Following traumatic brain injury, uncontrollable intracranial hypertension remains the most frequent cause of death. Despite general agreement on the deleterious effects of elevated intracranial pressure (ICP), however, the evidence supporting the use of ICP monitoring has recently been questioned. The aim of this review was to evaluate the pros and cons of ICP monitoring and to discuss the hypothetical desirability and feasibility of a trial testing the benefits of ICP monitoring.

  7. Scientific evidence for therapeutic effects of Chinese prescription Kangen-karyu from pre-clinical animal experiments.

    PubMed

    Yokozawa, Takako; Park, Chan Hum; Matsumoto, Kinzo

    2017-01-26

    Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports therapeutic evidence for Kangen-karyu from pre-clinical animal experiments related to human diseases. Kangen-karyu showed beneficial effects on type 1 diabetes and related complications through the suppression of protein expression related to advanced glycation endproducts and oxidative stress. Kangen-karyu reduced oxidative stress via the regulation of dyslipidemia, and also exerted a renoprotective effect mainly through its antioxidant properties during the development of diabetic nephropathy in type 2 diabetes. In addition, Kangen-karyu showed neuroprotective effects by attenuating the spatial memory impairment and neuronal death induced by diabetes. Kangen-karyu counteracted oxidative stress and ameliorated tissue damage possibly associated with aging. These findings provide scientific evidence to explain the efficacy of Kangen-karyu based on its underlying therapeutic effects.

  8. Enhanced Evidence-Based Chinese Medicine Clinical Practice Guidelines in Hong Kong: A Study Protocol for Three Common Diseases

    PubMed Central

    Shi, Nannan; Zhong, Linda L. D.; Han, XueJie; Ng, Bacon; Bian, Zhaoxiang; Lu, Aiping

    2015-01-01

    We presented a study protocol of developing Chinese medicine clinical practice guidelines for three common diseases in Hong Kong, including insomnia, chronic gastritis, and cerebral infarction. This research project will be conducted in three phases. First phase is the preparation stage which consists of the establishment of steering committee and panel. Second phase involves 6 steps, which are searching and identifying evidence, text mining process, Delphi survey, synthesizing of data, consensus conference, and drafting guidelines. In this phase, text mining technique, evidence-based method, and formal consensus method are combined to get consolidated supporting data as the source of CM CPGs. The final phase comprised external reviews, dissemination, and updating. The outputs from this project will provide three CM CPGs for insomnia, chronic gastritis, and cerebral infarction for Hong Kong local use. PMID:25815035

  9. Probiotic use in horses - what is the evidence for their clinical efficacy?

    PubMed

    Schoster, A; Weese, J S; Guardabassi, L

    2014-01-01

    The gastrointestinal microbiota is extremely important for human and animal health. Investigations into the composition of the microbiota and its therapeutic modification have received increasing interest in human and veterinary medicine. Probiotics are a way of modifying the microbiota and have been tested to prevent and treat diseases. Probiotics are proposed to exert their beneficial effects through various pathways. Production of antimicrobial compounds targeting intestinal pathogens, general immune stimulation, and colonization resistance are among these mechanisms. Despite widespread availability and use, scientific, peer-reviewed evidence behind commercial probiotic formulations in horses is limited. Additionally, quality control of commercial over-the-counter products is not tightly regulated. Although promising in vitro results have been achieved, in vivo health benefits have been more difficult to prove. Whether the ambiguous results are caused by strain selection, dosage selection or true lack of efficacy remains to be answered. Although these limitations exist, probiotics are increasingly used because of their lack of severe adverse effects, ease of administration, and low cost. This review summarizes the current evidence for probiotic use in equine medicine. It aims to provide veterinarians with evidence-based information on when and why probiotics are indicated for prevention or treatment of gastrointestinal disease in horses. The review also outlines the current state of knowledge on the equine microbiota and the potential of fecal microbial transplantation, as they relate to the topic of probiotics.

  10. Evidence supporting primary prevention of cardiovascular diseases with statins: Gaps between updated clinical results and actual practice.

    PubMed

    Bruckert, Eric; Ferrières, Jean

    2014-03-01

    The use of pharmacological lipid-lowering intervention in individuals with hypercholesterolaemia and known cardiovascular disease or diabetes/chronic kidney disease is well established. Current European Society of Cardiology guidelines recommend immediate initiation of drugs in adjunct to lifestyle intervention in these patients at high or very high cardiovascular risk. In these clinical settings, statins are generally chosen as the first-choice drug intervention, in consideration of the robust evidence showing a reduction in all-cause mortality and major adverse cardiac events (MACE). In contrast, primary prevention with statins, even in the subset of patients at high-risk of cardiovascular events, is not well implemented. This might be related to a lack of public awareness regarding the actual risk associated with prolonged exposure to high concentrations of low-density lipoprotein cholesterol (LDL-C) and uncertainties in the clinical evidence coming from the earliest trials in this patient subset. However, recent observational studies suggest that lowering LDL-C earlier in life and for a longer duration can substantially decrease the burden of cardiovascular disease and mortality. Moreover, results from recent well-conducted large meta-analyses of randomized clinical trials showed that primary prevention with statins reduced all-cause mortality by 14% and MACE by > 20% - findings similar to those observed for the use of statins in secondary prevention. Recently published American Heart Association/American College of Cardiology guidelines on the treatment of blood cholesterol emphasize that primary prevention using high-dose statins in individuals with LDL-C ≥ 190 mg/dL induces a benefit in atherosclerotic cardiovascular risk reduction that clearly exceeds the potential for adverse effects. We aim in this review to discuss the new data that advocate the use of statins in primary prevention earlier and more frequently, putting the efficacy evidence into

  11. The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment.

    PubMed

    Sciascia, Savino; Branch, D Ware; Levy, Roger A; Middeldorp, Saskia; Pavord, Sue; Roccatello, Dario; Ruiz-Irastorza, Guillermo; Tincani, Angela; Khamashta, Munther; Schreiber, Karen; Hunt, Beverley J

    2016-01-01

    The use of low-dose aspirin and heparinoids has improved the pregnancy outcome in obstetric antiphospholipid syndrome (APS). However, current treatment fails in 20-30% of APS pregnancies, raising the need to explore other treatments to improve obstetrical outcome. Hydroxychloroquine (HCQ) is widely used in patients with autoimmune diseases, mainly systemic lupus erythematous (SLE), due to its anti-inflammatory, anti-aggregant and immune-regulatory properties. Evidence from in vitro and animal models suggests a potential protective effect of HCQ in obstetric APS. Pending the availability of prospective trials, we aimed to systematically review the available evidence and to assess the clinical judgment of a panel of experts regarding the use of HCQ in improving pregnancy outcome in women with antiphospholipid antibodies (aPL). Clinical data on the ability of HCQ to improve pregnancy outcome in women with aPL are very limited in the available literature. Only one cohort study evaluating maternal and fetal outcome of pregnancy in patients with SLE who were exposed to HCQ was identified. Four of 14 (29%) treated with HCQ patients had pregnancy failure, compared with six of 24 (25%) of patients not treated with HCQ. However, the effect of HCQ was not adjusted for the use of other medications such as aspirin, heparins or steroids. Selected experts were contacted by e-mail and asked to review the summary of the evidence provided by the working group and to briefly answer each of the proposed questions. Overall, the panel of experts agreed that adding HCQ could be considered in selected cases or after failure of standard treatment with aspirin and a heparin agent. Specifically, the majority of experts considered adding HCQ in specific scenarios, such as women with previous thrombosis (either arterial and/or venous), and/or with previous ischaemic placenta-mediated complications. Prospective studies are necessary before the use of HCQ during pregnancy in women with a

  12. Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation.

    PubMed

    Blaze, Jennifer; Roth, Tania L

    2015-07-01

    While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess underlying epigenetic modifications. In this review, we highlight clinical research and work from animal models that provide evidence of the impact of stressful experiences either during the perinatal period or adulthood on DNA methylation and behavior. Additionally, we explore the more controversial concept of transgenerational inheritance, including that associated with preconception stress experienced by the mother or father. Finally, we discuss challenges associated with the idea of transgenerational epigenetics and for the field of epigenetics in general.

  13. A pilot project using evidence-based clinical pathways and payment reform in China's rural hospitals shows early success.

    PubMed

    Cheng, Tsung-Mei

    2013-05-01

    Reforming China's public hospitals to curb widespread overtreatment and improve the quality and affordability of care has been the most challenging aspect of that nation's ambitious health reform, which began in 2009. This article describes a pilot project under way in several of China's provinces that combines payment reform with the implementation of evidence-based clinical pathways at a few hospitals serving rural areas. Results to date include reduced length-of-stay and prescription drug use and higher patient and provider satisfaction. These early results suggest that the pilot may be achieving its goals, which may have far-reaching and positive implications for China's ongoing reform.

  14. Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation

    PubMed Central

    Blaze, Jennifer; Roth, Tania L.

    2015-01-01

    While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess epigenetic modifications associated with these consequences. In this review, we highlight clinical research and work with animal models that provide evidence of the impact of stressful experiences either during the perinatal period or adulthood on DNA methylation and behavior. Additionally, we explore the more controversial concept of transgenerational inheritance, including that associated with preconception stress experienced by the mother or father. Finally, we discuss challenges associated with the idea of transgenerational epigenetics and for the field of epigenetics in general. PMID:25917771

  15. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review

    PubMed Central

    Mazzeffi, Michael; Johnson, Kyle; Paciullo, Christopher

    2015-01-01

    Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review. PMID:25849690

  16. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    PubMed Central

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  17. Carney v Newton: expert evidence about the standard of clinical notes.

    PubMed

    Faunce, Thomas; Hammer, Ingrid; Jefferys, Susannah

    2007-12-01

    In Carney v Newton [2006] TASSC 4 the Tasmanian Supreme Court heard a claim that the defendant breached his duty of care by failing to properly diagnose and treat a node positive carcinoma in the plaintiff's breast tissue. At trial, argument turned on the actual dialogue that took place during the initial consultation, with significant reliance on the clinical notes of the defendant. The court gave considerable weight to "expert" witnesses in ascertaining the acceptability of the defendant's conduct concerning the maintenance and interpretation of his clinical notes. This raises important questions in relation to proof of quality of medical records as part of the current professional standard of care, as modified by recent legislation in most jurisdictions.

  18. Do current clinical trials meet society's needs?: a critical review of recent evidence.

    PubMed

    Pocock, Stuart J; Gersh, Bernard J

    2014-10-14

    This paper describes some important controversies regarding the current state of clinical trials research in cardiology. Topics covered include the inadequacy of trial research on medical devices, problems with industry-sponsored trials, the lack of head-to-head trials of new effective treatments, the need for wiser handling of drug safety issues, the credibility (or lack thereof) of trial reports in medical journals, problems with globalization of trials, the role of personalized (stratified) medicine in trials, the need for new trials of old drugs, the need for trials of treatment withdrawal, the importance of pragmatic trials of treatment strategies, and the limitations of observational comparative effectiveness studies. All issues are illustrated by recent topical trials in cardiology. Overall, we explore the extent to which clinical trials, as currently practiced, are successful in meeting society's expectations.

  19. Vonoprazan-based therapy for Helicobacter pylori eradication: experience and clinical evidence

    PubMed Central

    Akazawa, Yuko; Fukuda, Daisuke; Fukuda, Yutaka

    2016-01-01

    Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H. pylori eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors. PMID:27803739

  20. Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats

    PubMed Central

    Lovati, Arianna Barbara; Romanò, Carlo Luca; Bottagisio, Marta; Monti, Lorenzo; De Vecchi, Elena; Previdi, Sara; Accetta, Riccardo; Drago, Lorenzo

    2016-01-01

    S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (103, 105, 108 colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 103 group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 105 and 108 groups showed severe signs of osteomyelitis and a non-union rate of 83–100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical

  1. [Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives].

    PubMed

    Pinto, F; Calarco, A; Totaro, A; Sacco, E; Volpe, A; Racioppi, M; D'Addessi, A; Bassi, P F

    2010-01-01

    Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

  2. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence

    PubMed Central

    Pasieka, Aoibhe M.; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  3. Alterations of the subchondral bone in osteochondral repair--translational data and clinical evidence.

    PubMed

    Orth, P; Cucchiarini, M; Kohn, D; Madry, H

    2013-06-28

    Alterations of the subchondral bone are pathological features associated with spontaneous osteochondral repair following an acute injury and with articular cartilage repair procedures. The aim of this review is to discuss their incidence, extent and relevance, focusing on recent knowledge gained from both translational models and clinical studies of articular cartilage repair. Efforts to unravel the complexity of subchondral bone alterations have identified (1) the upward migration of the subchondral bone plate, (2) the formation of intralesional osteophytes, (3) the appearance of subchondral bone cysts, and (4) the impairment of the osseous microarchitecture as potential problems. Their incidence and extent varies among the different small and large animal models of cartilage repair, operative principles, and over time. When placed in the context of recent clinical investigations, these deteriorations of the subchondral bone likely are an additional, previously underestimated, factor that influences the long-term outcome of cartilage repair strategies. Understanding the role of the subchondral bone in both experimental and clinical articular cartilage repair thus holds great promise of being translated into further improved cell- or biomaterial-based techniques to preserve and restore the entire osteochondral unit.

  4. Denosumab treatment in the management of patients with advanced prostate cancer: clinical evidence and experience

    PubMed Central

    Hegemann, Miriam; Bedke, Jens; Stenzl, Arnulf; Todenhöfer, Tilman

    2017-01-01

    Osteoprotective therapies have become an essential component in the management of advanced prostate cancer (PC) patients as bone metastases (BMs) have a major impact on morbidity and mortality. Denosumab is a fully humanized antibody targeting the receptor activator of nuclear factor κB ligand (RANKL), which has been approved by the European Medicines Agency (EMA) in Europe and the United States (US) Food and Drug Administration (FDA) in the US for prevention of skeletal-related events (SREs) in patients with solid tumors and BMs, including PC. The clinical settings in which PC patients should be treated with denosumab are still discussed controversially. In a phase III study, denosumab significantly delayed SREs compared with zoledronic acid (ZA) in patients with metastatic castration-resistant PC (CRPC). In addition, denosumab showed superior effects on pain and health-related quality of life (QoL) in these patients. In patients with nonmetastatic CRPC, denosumab has been proven to significantly increase bone metastases-free survival. However, no significant benefits on cancer-specific and overall survival were observed and denosumab was not approved by the US FDA and EMA in this context. The effectiveness of denosumab in patients with castration-sensitive PC (CSPC) and BMs is also under discussion, as clinical trials with ZA in these patients have not shown significant benefits. Clinical data on the use of denosumab in CSPC are urgently needed. PMID:28392837

  5. Are clinical features able to predict Helicobacter pylori gastritis patterns? Evidence from tertiary centers.

    PubMed

    Carabotti, Marilia; Lahner, Edith; Porowska, Barbara; Colacci, Enzo; Trentino, Paolo; Annibale, Bruno; Severi, Carola

    2014-12-01

    Outcome of Helicobacter pylori infection is different according to gastritis extension (i.e. antrum-restricted gastritis or pangastritis). The aim of this study is to evaluate whether different gastritis patterns are associated with specific gastrointestinal symptoms or clinical signs that could be suggestive of the topography of gastritis. 236 consecutive symptomatic outpatients were recruited in two tertiary centers. They filled in a validated and self-administered Rome III modular symptomatic questionnaire, and underwent gastroscopy with histological sampling. 154 patients with Helicobacter pylori infection were included. Clinical presentation did not differ between antrum-restricted gastritis and pangastritis, gastro-esophageal reflux disease being present in 48.2 and 54.1 % of patients and dyspepsia in 51.8 and 45.9 %, respectively. However, pangastritis statistically differed from antrum-restricted gastritis in that the presence of clinical signs (p < 0.0001) was observed in 33.7 % of the patients, consisting of iron deficiency (31.6 %), iron deficiency-anemia (20.4 %) and levothyroxine malabsorption (3.1 %). Symptoms are not helpful in suggesting gastritis pattern whereas their association with signs, accurately detected, is indicative for the presence of pangastritis.

  6. Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

    PubMed Central

    2016-01-01

    Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose. PMID:27721835

  7. Evidence of the Internationalization of Clinical Endoscopy Based on Journal Metrics

    PubMed Central

    2015-01-01

    Background/Aims This study aims to verify the internationalization of Clinical Endoscopy based on journal metrics after the change to English-only in 2011. The results of this study serve as a starting point for developing strategies to develop Clinical Endoscopy into a top-tier international journal. Methods The following journal metrics were analyzed from the journal's homepage or the Web of Science: the number of citable articles, number of countries of affiliation of the contributors, the number of articles supported by research grants, total citations, impact factor, citing journals, countries of citing authors, and the Hirsch index. Results The number of citable articles in 2011, 2012, 2013, and 2014 was 22, 81, 120, and 95, respectively. The authors were from 11 countries. Twenty-one out of 55 original articles were supported by research grants. The total citations in 2012, 2013, and 2014 were 2, 85, and 213, respectively. The impact factor was 0.670 in 2013 and 0.940 in 2014. The number of countries citing authors were from was 61. The Hirsch index was 6. Conclusions The above results demonstrate that Clinical Endoscopy became an international journal, contributing to the propagation of valuable research results through an open access publishing model. PMID:26240806

  8. [Inhibition of RANK-L in the pathophysiology of osteoporosis. Clinical evidences of its use].

    PubMed

    Luis Neyro, José; Jesús Cancelo, María; Palacios, Santiago

    2013-03-01

    The increase bone turnover is the most important fact at the physiopathology of postmenopausal osteoporosis. At the molecular level it is the increase of the RANK-L the principal mediator who allows the osteoclasts formation, survival and development of them. Multiple models have been in use in preclinical investigations for evaluating the effects of the inhibition of the RANKL, between which it is included on OPG's over-expression in mice and transgenic mouse and by means of other models that include the treatment with recombinant OPG. The results of these studies show that RANKL's inhibition improves the DMO as well as the geometry and resistance of the bone. Several references clinical trials have investigated the potential of denosumab as antiresorptive drug for the prevention and treatment of bone disease. It is a monoclonal antibody, the first fully human, which were recently published results of randomized clinical trials to eight years for increasing BMD in different locations and five years for the prevention of vertebral and hip fractures. We review the fundamentals of the mechanism of inhibition of RANK-L and the results of several clinical trials of Denosumab.

  9. Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

    PubMed Central

    Natesan, Suganthini Krishnan; Chandrasekar, Pranatharthi H

    2016-01-01

    The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ) seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA) for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. PMID:27994475

  10. Clinical metric and medication persistency effects: evidence from a Medicaid care management program.

    PubMed

    Berg, Gregory D; Leary, Fredric; Medina, Wendie; Donnelly, Shawn; Warnick, Kathleen

    2015-02-01

    The objective was to estimate clinical metric and medication persistency impacts of a care management program. The data sources were Medicaid administrative claims for a sample population of 32,334 noninstitutionalized Medicaid-only aged, blind, or disabled patients with diagnosed conditions of asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes, or heart failure between 2005 and 2009. Multivariate regression analysis was used to test the hypothesis that exposure to a care management intervention increased the likelihood of having the appropriate medication or procedures performed, as well as increased medication persistency. Statistically significant clinical metric improvements occurred in each of the 5 conditions studied. Increased medication persistency was found for beta-blocker medication for members with coronary artery disease, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic medications for members with heart failure, bronchodilator and corticosteroid medications for members with chronic obstructive pulmonary disease, and aspirin/antiplatelet medications for members with diabetes. This study demonstrates that a care management program increases the likelihood of having an appropriate medication dispensed and/or an appropriate clinical test performed, as well as increased likelihood of medication persistency, in people with chronic conditions.

  11. Policies and Procedures That Facilitate Implementation of Evidence-Based Clinical Guidelines in U.S. Dental Schools.

    PubMed

    Polk, Deborah E; Nolan, Beth A D; Shah, Nilesh H; Weyant, Robert J

    2016-01-01

    The aim of this study was to determine the degree to which dental schools in the United States have policies and procedures in place that facilitate the implementation of evidence-based clinical guidelines. The authors sent surveys to all 65 U.S. dental schools in 2014; responses were obtained from 38 (58%). The results showed that, of the nine policies and procedures examined, only two were fully implemented by 50% or more of the responding schools: guidelines supported through clinical faculty education or available chairside (50%), and students informed of guidelines in both the classroom and clinic (65.8%). Although 92% of the respondents reported having an electronic health record, 80% of those were not using it to track compliance with guidelines. Five schools reported implementing more policies than the rest of the schools. The study found that the approach to implementing guidelines at most of the responding schools did not follow best practices although five schools had an exemplary set of policies and procedures to support guideline implementation. These results suggest that most dental schools are currently not implementing guidelines effectively and efficiently, but that the goal of schools' having a comprehensive implementation program for clinical guidelines is achievable since some are doing so. Future studies should determine whether interventions to improve implementation in dental schools are needed.

  12. Adopting evidence-based practice in clinical decision making: nurses' perceptions, knowledge, and barriers

    PubMed Central

    Majid, Shaheen; Foo, Schubert; Luyt, Brendan; Zhang, Xue; Theng, Yin-Leng; Chang, Yun-Ke; Mokhtar, Intan A

    2011-01-01

    Objective: Evidence-based practice (EBP) provides nurses with a method to use critically appraised and scientifically proven evidence for delivering quality health care to a specific population. The objective of this study was to explore nurses' awareness of, knowledge of, and attitude toward EBP and factors likely to encourage or create barriers to adoption. In addition, information sources used by nurses and their literature searching skills were also investigated. Method: A total of 2,100 copies of the questionnaire were distributed to registered nurses in 2 public hospitals in Singapore, and 1,486 completed forms were returned, resulting in a response rate of 70.8%. Results: More than 64% of the nurses expressed a positive attitude toward EBP. However, they pointed out that due to heavy workload, they cannot keep up to date with new evidence. Regarding self-efficacy of EBP-related abilities, the nurses perceived themselves to possess moderate levels of skills. The nurses also felt that EBP training, time availability, and mentoring by nurses with EBP experience would encourage them to implement EBP. The top three barriers to adopting EBP were lack of time, inability to understand statistical terms, and inadequate understanding of the jargon used in research articles. For literature searching, nurses were using basic search features and less than one-quarter of them were familiar with Boolean and proximity operators. Conclusion: Although nurses showed a positive attitude toward EBP, certain barriers were hindering their smooth adoption. It is, therefore, desirable that hospital management in Southeast Asia, particularly in Singapore, develop a comprehensive strategy for building EBP competencies through proper training. Moreover, hospital libraries should also play an active role in developing adequate information literacy skills among the nurses. PMID:21753915

  13. Mesomelic dysplasia, Kantaputra type: clinical report, prenatal diagnosis, no evidence for SHOX deletion/mutation.

    PubMed

    Kwee, M L; van de Sluijs, J A; van Vugt, J M G; Wijnaendts, L C D; Gille, J J P

    2004-08-01

    A grandmother, her three children, and three grandchildren had skeletal abnormalities consisting of a short stature, bilateral symmetrical very short, broad and bowed radii, very short and broad ulna, mildly short lower legs, short proximal end of fibula, abnormal ankles, abnormal calcaneus and talus and pes equinus. They had normal craniofacial features, normal intelligence and normal chromosomes. We concluded that this skeletal dysplasia resembles the autosomal dominant mesomelic dysplasia, Kantaputra type. Prenatal diagnosis by ultrasound examination early in the pregnancy was possible. We found no evidence for a SHOX gene deletion or point mutation. As far as we know this is the third reported family with this skeletal dysplasia.

  14. [Evidences of physical agents action on bone metabolism and their potential clinical use].

    PubMed

    Lirani, Ana Paula R; Lazaretti-Castro, Marise

    2005-12-01

    The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature.

  15. Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain

    PubMed Central

    Bhatnagar, Sushma; Gupta, Maynak

    2015-01-01

    Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10–15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician's armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients. PMID:26009665

  16. Evidence-based Clinical Practice Guidelines for Interventional Pain Management in Cancer Pain.

    PubMed

    Bhatnagar, Sushma; Gupta, Maynak

    2015-01-01

    Intractable cancer pain not amenable to standard oral or parenteral analgesics is a horrifying truth in 10-15% of patients. Interventional pain management techniques are an indispensable arsenal in pain physician's armamentarium for severe, intractable pain and can be broadly classified into neuroablative and neuromodulation techniques. An array of neurolytic techniques (chemical, thermal, or surgical) can be employed for ablation of individual nerve fibers, plexuses, or intrathecalneurolysis in patients with resistant pain and short life-expectancy. Neuraxial administration of drugs and spinal cord stimulation to modulate or alter the pain perception constitutes the most frequently employed neuromodulation techniques. Lately, there is a rising call for early introduction of interventional techniques in carefully selected patients simultaneously or even before starting strong opioids. After decades of empirical use, it is the need of the hour to head towards professionalism and standardization in order to secure credibility of specialization and those practicing it. Even though the interventional management has found a definite place in cancer pain, there is a dearth of evidence-based practice guidelines for interventional therapies in cancer pain. This may be because of paucity of good quality randomized controlled trials (RCTs) evaluating their safety and efficacy in cancer pain. Laying standardized guidelines based on existing and emerging evidence will act as a foundation step towards strengthening, credentialing, and dissemination of the specialty of interventional cancer pain management. This will also ensure an improved decision-making and quality of life (QoL) of the suffering patients.

  17. Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence

    PubMed Central

    Perego, S; Sansoni, V; Diani, M; Banfi, G; Altomare, G

    2016-01-01

    Objective Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design Case–control, longitudinal. Setting Single centre. Participants Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals. Interventions All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures. PMID:27940624

  18. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

    PubMed Central

    Dürsteler, Kenneth M; Berger, Eva-Maria; Strasser, Johannes; Caflisch, Carlo; Mutschler, Jochen; Herdener, Marcus; Vogel, Marc

    2015-01-01

    Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by

  19. Evidence for association of hyperprolinemia with schizophrenia and a measure of clinical outcome.

    PubMed

    Clelland, Catherine L; Read, Laura L; Baraldi, Amanda N; Bart, Corinne P; Pappas, Carrie A; Panek, Laura J; Nadrich, Robert H; Clelland, James D

    2011-09-01

    There are multiple genetic links between schizophrenia and a deficit of proline dehydrogenase (PRODH) enzyme activity. However, reports testing for an association of schizophrenia with the resulting proline elevation have been conflicting. The objectives of this study were to investigate whether hyperprolinemia is associated with schizophrenia, and to measure the relationship between plasma proline, and clinical features and symptoms of schizophrenia. We performed a cross-sectional case-control study, comparing fasting plasma proline in 90 control subjects and 64 schizophrenic patients and testing for association of mild to moderate hyperprolinemia with schizophrenia. As secondary analyses, the relationship between hyperprolinemia and five measures of clinical onset, symptoms and outcome were investigated. Patients had significantly higher plasma proline than matched controls (p<0.0001), and categorical analysis of gender adjusted hyperprolinemia showed a significant association with schizophrenia (OR 6.15, p=0.0003). Hyperprolinemic patients were significantly older at their first hospitalization (p=0.015 following correction for multiple testing). While plasma proline level was not related to total, positive or negative symptoms, hyperprolinemic status had a significant effect on length of hospital stay (p=0.005), following adjustment for race, BPRS score, and cross-sectional time from admission to proline measurement. Mild to moderate hyperprolinemia is a significant risk factor for schizophrenia, and may represent an intermediate phenotype in the disease. Hyperprolinemic patients have a significantly later age of first psychiatric hospitalization, suggestive of later onset, and hospital stays 46% longer than non-hyperprolinemic subjects. These findings have implications in the etiology of schizophrenia, and for the clinical management of these patients.

  20. Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 2

    PubMed Central

    McRorie, Johnson W.

    2015-01-01

    Dietary fiber that is intrinsic and intact in fiber-rich foods (eg, fruits, vegetables, legumes, whole grains) is widely recognized to have beneficial effects on health when consumed at recommended levels (25 g/d for adult women, 38 g/d for adult men). Most (90%) of the US population does not consume this level of dietary fiber, averaging only 15 g/d. In an attempt to bridge this “fiber gap,” many consumers are turning to fiber supplements, which are typically isolated from a single source. Fiber supplements cannot be presumed to provide the health benefits that are associated with dietary fiber from whole foods. Of the fiber supplements on the market today, only a minority possess the physical characteristics that underlie the mechanisms driving clinically meaningful health benefits. In this 2-part series, the first part (previous issue) described the 4 main characteristics of fiber supplements that drive clinical efficacy (solubility, degree/rate of fermentation, viscosity, and gel formation), the 4 clinically meaningful designations that identify which health benefits are associated with specific fibers, and the gel-dependent mechanisms in the small bowel that drive specific health benefits (eg, cholesterol lowering, improved glycemic control). The second part (current issue) of this 2-part series will focus on the effects of fiber supplements in the large bowel, including the 2 mechanisms by which fiber prevents/relieves constipation (insoluble mechanical irritant and soluble gel-dependent water-holding capacity), the gel-dependent mechanism for attenuating diarrhea and normalizing stool form in irritable bowel syndrome, and the combined large bowel/small bowel fiber effects for weight loss/maintenance. The second part will also discuss how processing for marketed products can attenuate efficacy, why fiber supplements can cause gastrointestinal symptoms, and how to avoid symptoms for better long-term compliance. PMID:25972619

  1. Onset Time of Tumor Repopulation for Cervical Cancer: First Evidence From Clinical Data

    SciTech Connect

    Huang Zhibin; Mayr, Nina A.; Gao, Mingcheng; Lo, Simon S.; Wang, Jian Z.; Jia Guang; Yuh, William T.C.

    2012-10-01

    Purpose: Accelerated tumor repopulation has significant implications in low-dose rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer, using clinical data. Methods and Materials: The linear quadratic (LQ) model extended for tumor repopulation was used to analyze clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least {chi}{sup 2} method was used to fit the TCP data with two free parameters: onset time (T{sub k}) of accelerated repopulation and number of clonogens (K), while other LQ model parameters were adopted from the literature, due to the limited patient data. Results: Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated with higher TCP. Using the LQ model, we achieved the best fit with onset time T{sub k} of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T{sub k} and (48, 1822) for K, respectively. Conclusion: This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.

  2. Ibrutinib in Waldenström macroglobulinemia: latest evidence and clinical experience

    PubMed Central

    Castillo, Jorge J.; Palomba, M. Lia; Advani, Ranjana; Treon, Steven P.

    2016-01-01

    Ibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events. PMID:27493708

  3. The relationship between opioid and sugar intake: Review of evidence and clinical applications

    PubMed Central

    Mysels, David J; Sullivan, Maria A

    2011-01-01

    Opioid dependence poses significant public health risks arising from associated morbidity and mortality caused by accidents, infectious disease, and social ramifications of crime and unemployment, among other complications. Opioid use, acute and chronic, is also associated with weight gain, glycemic dysregulation, and dental pathology. The literature supporting the connection between opiate use and development of preference for sweet tastes is reviewed, and further association with dental pathology, weight gain, and loss of glycemic control are considered. We discuss the impact of sweet tastes on the endogenous opioid system as well as clinical implications for analgesia and treating the opiate-dependent patient. PMID:21269006

  4. Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.

    PubMed

    Russo, Antonio; Fratto, Maria E; Bazan, Viviana; Schiró, Valentina; Agnese, Valentina; Cicero, Giuseppe; Vincenzi, Bruno; Tonini, Giuseppe; Santini, Daniele

    2007-12-01

    The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level.

  5. Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes

    PubMed Central

    Iyer, Srinivasan V.; LePendu, Paea; Olson, Cliff; Shah, Nigam H.

    2013-01-01

    Background Peripheral arterial disease (PAD) is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF). Methods and Results We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1∶5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55]), myocardial infarction (OR = 1.00, CI [0.71, 1.39]), or death (OR = 0.86, CI [0.63, 1.18]). Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients. Conclusions This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover ‘natural experiments’ such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy. PMID:23717437

  6. Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence

    PubMed Central

    Du, Yixing; Xu, Xiaohan; Chu, Ming; Guo, Yan

    2016-01-01

    Air pollution is now becoming an independent risk factor for cardiovascular morbidity and mortality. Numerous epidemiological, biomedical and clinical studies indicate that ambient particulate matter (PM) in air pollution is strongly associated with increased cardiovascular disease such as myocardial infarction (MI), cardiac arrhythmias, ischemic stroke, vascular dysfunction, hypertension and atherosclerosis. The molecular mechanisms for PM-caused cardiovascular disease include directly toxicity to cardiovascular system or indirectly injury by inducing systemic inflammation and oxidative stress in peripheral circulation. Here, we review the linking between PM exposure and the occurrence of cardiovascular disease and discussed the possible underlying mechanisms for the observed PM induced increases in cardiovascular morbidity and mortality. PMID:26904258

  7. Gingival recession and adult orthodontics: a clinical evidence-based treatment proposal.

    PubMed

    Dersot, Jean-Marc

    2012-03-01

    The presence of a gingival recession prior to orthodontic treatment is a real problem. Patients are concerned about losing their teeth but may also complain of their unpleasant appearance or root sensitivity in the exposed area. The orthodontist is not sure whether orthodontic treatment can be performed or whether the tooth movement will not aggravate the recession and whether periodontal surgery needs to be done before or after orthodontic treatment. The aim of this paper is to present recent data from the literature and several clinical situations in adults in order to submit a treatment sequence and clarify the role of different periodontal plastic surgery root coverage procedures.

  8. Belimumab in systemic lu