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Sample records for accumulating clinical evidence

  1. Evidence accumulation for spatial reasoning

    NASA Technical Reports Server (NTRS)

    Matsuyama, T.; Hwang, V. S. S.; Davis, L. S.

    1984-01-01

    The evidence accumulation proces of an image understanding system is described enabling the system to perform top-down(goal-oriented) picture processing as well as bottom-up verification of consistent spatial relations among objects.

  2. [Significance of Tc-99m pyrophosphate accumulation in unstable angina: clinical characteristics and evidence for myocardial stunning].

    PubMed

    Tange, S; Kondo, C; Ohta, Y; Kusakabe, K; Shigeta, A; Uchida, T; Sumiyoshi, T; Kaneko, N; Hosoda, S

    1993-01-01

    Tc-99m pyrophosphate (PYP) and Tl-201 simultaneous dual energy single photon emission computed tomography (SPECT) were performed for 33 patients with clinically diagnosed unstable angina. Twenty-two patients (76%) showed PYP accumulation in the myocardium (PYP+group). Clinical features, types of unstable angina, electrocardiographic changes during and after the anginal attack, and serial creatine kinase (CK) sampling data were reviewed and compared in the 2 groups. Selective coronary angiography was performed in all patients, and contrast left ventriculography was carried out in 29 patients both in unstable and stable states. In the study of left ventriculograms, the ejection fraction (EF) was calculated by the area-length method and the wall motion abnormality index was calculated by the centerline method. The PYP(+)group differed significantly from the PYP(-)group in several features as follows: 1) the "new angina at rest" type of unstable angina was more frequent in the PYP(+)group than in the PYP(-)group. The ratios of new angina at rest/effort angina (including new angina of effort and angina of effort with changing pattern) were 16/6; 2/9 for the PYP(+) and (-)groups, respectively (p < 0.05). 2) ST elevation during the heart attack was seen more in the PYP(+)group. The ratios of ST elevation/ST depression were 13/22 (59%); 5/22 (23%) for the PYP(+)group, and 2/11 (18%); 7/11 (64%) for the PYP(-)group, respectively (p < 0.05). 3) EF was improved in the PYP(+) group to the normal range. EF in the PYP(+)group changed from 57 +/- 12 in the unstable state to 62 +/- 11% in the stable state (p < 0.02), while that of the PYP(-)group showed no significant difference between the unstable state (59 +/- 9%) and the stable state (59 +/- 11%). 4) Wall motion abnormality index (WMI) in the PYP(+)group was poorer than in the PYP(-)group, but it improved markedly in one month to the same level as that of the PYP(-)group. WMI in the PYP(+)group in the unstable state (21

  3. 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

  4. 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.

  5. Evidence of aluminium accumulation in aluminium welders.

    PubMed Central

    Elinder, C G; Ahrengart, L; Lidums, V; Pettersson, E; Sjögren, B

    1991-01-01

    Using atomic absorption spectrometry the aluminium concentrations in blood and urine and in two iliac bone biopsies obtained from welders with long term exposure to fumes containing aluminium were measured. The urinary excretion of two workers who had welded for 20 and 21 years varied between 107 and 351 micrograms Al/l, more than 10 times the concentration found in persons without occupational exposure. Urinary aluminium excretion remained high many years after stopping exposure. Blood and bone aluminium concentrations (4-53 micrograms Al/l and 18-29 micrograms Al/g respectively) were also raised but not to the same extent as urine excretion. It is concluded that long term exposure to aluminium by inhalation gives rise to accumulation of aluminium in the body and skeleton of health persons, and that the elimination of retained aluminium is very slow, in the order of several years. PMID:1954151

  6. 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

  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. 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

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

    NASA Astrophysics Data System (ADS)

    Dehaene, Stanislas

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

  10. Active inference, evidence accumulation and the urn task

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. Is There Neural Evidence for an Evidence Accumulation Process in Memory Decisions?

    PubMed Central

    van Vugt, Marieke K.; Beulen, Marijke A.; Taatgen, Niels A.

    2016-01-01

    Models of evidence accumulation have been very successful at describing human decision making behavior. Recent years have also seen the first reports of neural correlates of this accumulation process. However, these studies have mostly focused on perceptual decision making tasks, ignoring the role of additional cognitive processes like memory retrieval that are crucial in real-world decisions. In this study, we tried to find a neural signature of evidence accumulation during a recognition memory task. To do this, we applied a method we have successfully used to localize evidence accumulation in scalp EEG during a perceptual decision making task. This time, however, we applied it to intracranial EEG recordings, which provide a much higher spatial resolution. We identified several brain areas where activity ramps up over time, but these neural patterns do not appear to be modulated by behavioral variables such as the amount of available evidence or response time. This casts doubt on the idea of evidence accumulation as a general decision-making mechanism underlying different types of decisions. PMID:27014024

  13. 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.

  14. 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

  15. Loess is the accumulation of dust, not evidence for aridity

    NASA Astrophysics Data System (ADS)

    Zech, Roland

    2013-04-01

    Loess-paleosol sequences (LPS) are valuable terrestrial archives for Quaternary climate and environmental changes. The famous sections on the Chinese Loess Plateau, for example, document the alternation of warm and humid interglacials (paleosols) and cold and more arid glacials (loess). This, at least partly, reflects the weakening of the monsoonal circulation during glacials and has led to the notion that loess in general documents more arid conditions. Paleosols, on the other hand, are often interpreted to document more humid conditions. We studied the LPS Crvenka in the Carpathian Basin, southeast Europe, which spans the full last glacial cycle, and obtained results that do not fit the above concept: (i) The analysis of plant-derived long-chain n-alkanes indicates the presence of deciduous trees and shrubs during glacials, i.e. sufficient precipitation for tree growth, whereas tree-less grass steppes seem to have prevailed during the Eemian, the last interglacial. (ii) Compound-specific deuterium analyses on the alkanes show only little changes on glacial-interglacial timescale. When compared with the isotopic enrichment of the Mediterranean Sea during the last glacial, this likely documents a combination of increased rainfall, reduced evapo-transpiration and reduced temperatures. (iii) Novel lipid biomarkers derived from soil bacteria (GDGTs, glycerol dialkyl glycerol tetraethers) also indicate humid glacials (BIT index close to 1) and more arid interglacials (BIT<0.8). Our results are in good agreement with modelling studies suggesting a southward shift of the westerlies during glacials, and aridization in the Mediterranean area in response to man-made global warming. More importantly, they remind us of an important fact: Loess is the accumulation of dust, but not (necessarily) evidence for aridity. Pedogenesis may simply not have been able to keep pace with high glacial dust accumulation rates related to intense glacial, periglacial and fluvial activity

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

    PubMed

    Takahashi, Masanobu

    2016-06-01

    Immune checkpoint blockade therapy has recently attracted great attention in the area of oncology. In Japan, since 2014, an anti-PD-1antibody nivolumab and anti-CTLA-4 antibody ipilimumab have been available for the treatment of patients with malignant melanoma, and nivolumab has been available for patients with non-small cell lung cancer. Clinical trials using these drugs and other immune checkpoint inhibitors are currently in progress worldwide. The immune checkpoint blockade therapy is a promising new cancer therapy; however, not all patients with cancer can benefit from this therapy. Recent evidence shows that markers reflecting the extent of genetic mutation accumulation, including mutation burden, non-synonymous mutation that produces neoantigen, and microsatellite instability, possibly serve as promising marker to predict who can benefit from the immune checkpoint blockade therapy. Here, I introduce the recent evidence and discuss the correlation between genetic mutation accumulation and clinical outcome of immune checkpoint blockade therapy. PMID:27306805

  17. 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

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

    PubMed

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

    2015-01-01

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

  19. Action Planning and the Timescale of Evidence Accumulation

    PubMed Central

    Donner, Tobias H.

    2015-01-01

    Perceptual decisions are based on the temporal integration of sensory evidence for different states of the outside world. The timescale of this integration process varies widely across behavioral contexts and individuals, and it is diagnostic for the underlying neural mechanisms. In many situations, the decision-maker knows the required mapping between perceptual evidence and motor response (henceforth termed “sensory-motor contingency”) before decision formation. Here, the integrated evidence can be directly translated into a motor plan and, indeed, neural signatures of the integration process are evident as build-up activity in premotor brain regions. In other situations, however, the sensory-motor contingencies are unknown at the time of decision formation. We used behavioral psychophysics and computational modeling to test if knowledge about sensory-motor contingencies affects the timescale of perceptual evidence integration. We asked human observers to perform the same motion discrimination task, with or without trial-to-trial variations of the mapping between perceptual choice and motor response. When the mapping varied, it was either instructed before or after the stimulus presentation. We quantified the timescale of evidence integration under these different sensory-motor mapping conditions by means of two approaches. First, we analyzed subjects’ discrimination threshold as a function of stimulus duration. Second, we fitted a dynamical decision-making model to subjects’ choice behavior. The results from both approaches indicated that observers (i) integrated motion information for several hundred ms, (ii) used a shorter than optimal integration timescale, and (iii) used the same integration timescale under all sensory-motor mappings. We conclude that the mechanisms limiting the timescale of perceptual decisions are largely independent from long-term learning (under fixed mapping) or rapid acquisition (under variable mapping) of sensory

  20. Respirators versus medical masks: evidence accumulates but the jury remains out

    PubMed Central

    Killingley, Ben

    2011-01-01

    Please cite this paper as: Killingley (2011). Respiratory versus medical masks: evidence accumulates but the jury remains out. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00237.x. PMID:21477131

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

    ERIC Educational Resources Information Center

    Norris, Dennis; Kinoshita, Sachiko

    2008-01-01

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

  2. 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

  3. 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. PMID:26261322

  4. Rhythmic fluctuations in evidence accumulation during decision making in the human brain

    PubMed Central

    Wyart, Valentin; de Gardelle, Vincent; Scholl, Jacqueline; Summerfield, Christopher

    2014-01-01

    Summary Categorical choices are preceded by the accumulation of sensory evidence in favour of one action or another. Current models describe evidence accumulation as a continuous process occurring at a constant rate, but this view is inconsistent with accounts of a psychological refractory period during sequential information processing. During multi-sample perceptual categorisation, we found that the neural encoding of momentary evidence in human electrical brain signals and its subsequent impact on choice fluctuated rhythmically according to the phase of ongoing parietal delta oscillations (1-3 Hz). By contrast, lateralised beta-band power (10-30 Hz) overlying human motor cortex encoded the integrated evidence as a response preparation signal. These findings draw a clear distinction between central and motor stages of perceptual decision making, with successive samples of sensory evidence competing to pass through a serial processing bottleneck before being mapped onto action. PMID:23177968

  5. 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

  6. Valerian: no evidence for clinically relevant interactions.

    PubMed

    Kelber, Olaf; Nieber, Karen; Kraft, Karin

    2014-01-01

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

  7. Evidence-based Clinical Management of Acute Malignant Colorectal Obstruction.

    PubMed

    Shimura, Takaya; Joh, Takashi

    2016-04-01

    Acute malignant colorectal obstruction (AMCO) is an emergency associated with colorectal cancer (CRC). Emergency surgery is standard therapy for AMCO, and 1-stage surgery without colostomy is preferable, but it is occasionally difficult in the emergency setting. A self-expandable metallic stent (SEMS) enables noninvasive colonic decompression and subsequent 1-stage surgery, which has been widely applied for CRC with AMCO. However, recent accumulation of high-quality evidence has highlighted some problems and the limited efficacy of SEMS for AMCO. In palliative settings, SEMS placement reduces hospital stay and short-term complication rates, whereas it increases the frequency of long-term complications, such as delayed perforation. SEMS placement does not seem compatible with recent standard chemotherapy including bevacizumab. As a bridge to surgery, while SEMS placement provides a lower clinical success rate than emergency surgery, it can facilitate primary anastomosis without stoma. However, evidence regarding long-term survival outcomes with SEMS in both palliative and bridge to surgery settings is lacking. The efficacy of transanal colorectal tube placement, another endoscopic treatment, has been reported, but its clinical evidence level is low due to the limited number of studies. This review article comprehensively summarizes the current knowledge about surgical and endoscopic management of CRC with AMCO. PMID:26796083

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

    PubMed Central

    Tremel, Joshua J.; Wheeler, Mark E.

    2015-01-01

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

  9. Ambulance officers' use of online clinical evidence

    PubMed Central

    Westbrook, Johanna I; Westbrook, Mary T; Gosling, A Sophie

    2006-01-01

    Background Hospital-based clinicians have been shown to use and attain benefits from online evidence systems. To our knowledge there have been no studies investigating whether and how ambulance officers use online evidence systems if provided. We surveyed ambulance officers to examine their knowledge and use of the Clinical Information Access Program (CIAP), an online evidence system providing 24-hour access to information to support evidence-based practice. Methods A questionnaire was completed by 278 ambulance officers in New South Wales, Australia. Comparisons were made between those who used CIAP and officers who had heard of, but not used CIAP. Results Half the sample (48.6%) knew of, and 28.8% had used CIAP. Users were more likely to have heard of CIAP from a CIAP representative/presentation, non-users from written information. Compared to ambulance officers who had heard of but had not used CIAP, users were more likely to report better computer skills and that their supervisors regarded use of CIAP as a legitimate part of ambulance officers' clinical role. The main reasons for non-use were lack of access(49.0%) and training(31.4%). Of users, 51.3% rated their skills at finding information as good/very good, 67.5% found the information sought all/most of the time, 87.3% believed CIAP had the potential to improve patient care and 28.2% had directly experienced this. Most access to CIAP occurred at home. The databases frequently accessed were MIMS (A medicines information database) (73.8%) and MEDLINE(67.5%). The major journals accessed were Journal of Emergency Nursing(37.5%), American Journal of Medicine(30.0%) and JAMA(27.5%). Conclusion Over half of ambulance officers had not heard of CIAP. The proportion who knew about and used CIAP was also low. Reasons for this appear to be a work culture not convinced of CIAP's relevance to pre-hospital patient care and lack of access to CIAP at work. Ambulance officers who used CIAP accessed it primarily from home and

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

    PubMed

    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. PMID:26673896

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

    PubMed

    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. PMID:25869470

  12. 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

  13. Evidence accumulation in a complex task: Making choices about concurrent multiattribute stimuli under time pressure.

    PubMed

    Palada, Hector; Neal, Andrew; Vuckovic, Anita; Martin, Russell; Samuels, Kate; Heathcote, Andrew

    2016-03-01

    Evidence accumulation models transform observed choices and associated response times into psychologically meaningful constructs such as the strength of evidence and the degree of caution. Standard versions of these models were developed for rapid (∼1 s) choices about simple stimuli, and have recently been elaborated to some degree to address more complex stimuli and response methods. However, these elaborations can be difficult to use with designs and measurements typically encountered in complex applied settings. We test the applicability of 2 standard accumulation models-the diffusion (Ratcliff & McKoon, 2008) and the linear ballistic accumulation (LBA) (Brown & Heathcote, 2008)-to data from a task representative of many applied situations: the detection of heterogeneous multiattribute targets in a simulated unmanned aerial vehicle (UAV) operator task. Despite responses taking more than 2 s and complications added by realistic features, such as a complex target classification rule, interruptions from a simultaneous UAV navigation task, and time pressured choices about several concurrently present potential targets, these models performed well descriptively. They also provided a coherent psychological explanation of the effects of decision uncertainty and workload manipulations. Our results support the wider application of standard evidence accumulation models to applied decision-making settings. PMID:26844369

  14. 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. PMID:19199091

  15. Bazedoxifene: literature data and clinical evidence

    PubMed Central

    Lello, Stefano; Brandi, Maria Luisa; Minisola, Giovanni; Minisola, Salvatore; Genazzani, Andrea Riccardo

    2011-01-01

    Summary A Multidisciplinary National Panel of Experts in the management of Menopause and Postmenopausal Osteoporosis was created to determine the specific positioning of Bazedoxifene acetate (BZA), a third-generation selective estrogen receptor modulator (SERM), in the field of available therapeutic options in prevention and treatment of postmenopausal osteoporosis. There are various therapeutic options in prevention and treatment for postmenopausal osteoporosis, but nevertheless the problem of osteoporosis and osteoporosis-related fractures is not yet resolved today. In view of this unmet medical need, to have new treatments with efficacy and safety profile so good to therapeutically manage even larger groups of population is the conceptual basis to reduce the devastating impact of this disease on individual’s morbidity and mortality, and on public health expense. The Panel has, moreover, pointed up the need to increase the awareness about the issue “osteopenia” as a risk factor for fracture to consider in daily clinical practice and the opportunity to evaluate fracture risk using an adequate algorithm (for example, FRAX®, deFRA®), which integrates the result obtained by densitometry (Bone Mineral Density, BMD) (1, 2) and clinical risk factors, in order to consider threshold values for pharmacological intervention. As for prevention and treatment and different groups of age in women’s life, it is evident as in the group ranging in age 50 to 65 years the reference Specialist may be the Gynecologist, as the Woman’s doctor, even if other Specialists could be interested (Endocrinologist, Rheumatologist, Internist, General Practitioner, or other Specialist who is seeing a patient with osteopenia/osteoporosis). The involved Specialist, necessarily, has to make preventative and/or therapeutic strategies for osteopenia/osteoporosis. After the publication of the study Women’s Health Initiative (WHI) in 2002 (3), there was a decrease in applying Hormonal

  16. Cadmium as a possible cause of bladder cancer: a review of accumulated evidence.

    PubMed

    Feki-Tounsi, Molka; Hamza-Chaffai, Amel

    2014-09-01

    Bladder cancer is a significant disease, the rates of which have increased over the few last years. However, its etiology remains as yet undefined. Cadmium, a widespread environmental carcinogen that has received considerable interest, presents evidence as a possible cause of bladder cancer. A literature review was conducted from the years 1984-2013 to study the accumulated evidence for cadmium as a possible cause of bladder cancer, including routes of cadmium exposure, accumulation, toxicity, carcinogenicity, and evidence from epidemiological and experimental studies. Special reference is devoted to cadmium nephrotoxicity, which illustrates how cadmium exerts its effects on the transitional epithelium of the urinary tract. Mechanisms of carcinogenesis are discussed. The effects of cadmium on gene expression in urothelial cells exposed to cadmium are also addressed. Despite different methodologies, several epidemiologic and nephrotoxicity studies of cadmium indicate that occupational exposure to cadmium is associated with increased risk of bladder cancer and provide additional evidence that cadmium is a potential toxic element in urothelial cells. In vitro studies provide further evidence that cadmium is involved in urothelial carcinogenesis. Animal studies encounter several problems such as morphology differences between species. Among the complex mechanisms of cadmium carcinogenesis, gene expression deregulation is the subject of recent studies on bladder cadmium-induced carcinogenesis. Further research, however, will be required to promise a better understanding of the mechanisms underlying cadmium carcinogenesis and to establish the precise role of cadmium in this important malignancy. PMID:24894749

  17. Mental exercises for cognitive function: clinical evidence.

    PubMed

    Kawashima, Ryuta

    2013-01-01

    The purpose of this study was to examine the beneficial effects of a new cognitive intervention program designed for the care and prevention of dementia, namely Learning Therapy. The training program used systematized basic problems in arithmetic and Japanese language as training tasks. In study 1, 16 individuals in the experimental group and 16 in the control group were recruited from a nursing home. In both groups, all individuals were clinically diagnosed with senile dementia of the Alzheimer type. In study 2, we performed a single-blind, randomized controlled trial in our cognitive intervention program of 124 community-dwelling seniors. In both studies, the daily training program using reading and arithmetic tasks was carried out approximately 5 days a week, for 15 to 20 minutes a day in the intervention groups. Neuropsychological measures were determined simultaneously in the groups both prior to and after six months of the intervention. The results of our investigations indicate that our cognitive intervention using reading and arithmetic problems demonstrated a transfer effect and they provide convincing evidence that cognitive training maintains and improves the cognitive functions of dementia patients and healthy seniors. PMID:23412645

  18. Intravenous balanced solutions: from physiology to clinical evidence.

    PubMed

    Langer, Thomas; Santini, Alessandro; Scotti, Eleonora; Van Regenmortel, Niels; Malbrain, Manu L N G; Caironi, Pietro

    2015-01-01

    "Balanced" solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. Recently, the term "balanced" solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered and supra-physiologic in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental effect on renal function associated with hyperchloremia. Despite efforts for its identification, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available. After the accumulation of pre-clinical and clinical physiologic data, in the last three years, several clinical trials, mostly observational and retrospective, have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival. Nonetheless, the first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solution on renal function in critically-ill patients (SPLIT trial, the 0.9% Saline vs Plasma-Lyte 148 for Intensive Cate Unit Fluid Therapy), just recently published, showed identical equipoise between the two treatments. In the present review, we offer a comprehensive and updated summary on this issue, firstly, by providing a full physiological background of balanced solutions, secondly, by summarizing their potential pathophysiologic effects, and lastly, by presenting the clinical evidence available to support, at the moment, their use. PMID:26588483

  19. Clinical and economic evidence for intravenous acetaminophen.

    PubMed

    Yeh, Yu-Chen; Reddy, Prabashni

    2012-06-01

    Intravenous acetaminophen received United States Food and Drug Administration approval in November 2010 for the management of mild-to-moderate pain, management of moderate-to-severe pain with adjunctive opioid analgesics, and reduction of fever. Although intravenous acetaminophen generally improved pain relief and demonstrated opioid-sparing effects compared with placebo, it did not consistently reduce the frequency of opioid-related adverse events (e.g., postoperative nausea and vomiting). The safety and efficacy of intravenous acetaminophen as an antipyretic agent have been documented in adults and children; however, its cost is several-fold higher than that of the oral and rectal formulations. Although use of intravenous acetaminophen has reduced other postoperative resource utilization (e.g., hospital length of stay) in some studies outside the United States in patients undergoing abdominal surgery, a full economic evaluation in the United States has yet to be undertaken. In addition, its administration time (15-min infusion) and packaging (glass, single-use vial) have the potential to adversely affect patient flow in the postanesthesia care unit, create burden on patient care units, and lead to drug waste. Furthermore, 1 g of intravenous acetaminophen is formulated in 100 ml of solution, which may be an issue for patients with fluid restrictions. Given the clinical and economic evidence currently available, intravenous acetaminophen should not replace oral or rectal acetaminophen, but its use may be considered in a limited number of patients who cannot receive drugs orally and rectally and who cannot tolerate other parenteral nonopioid analgesic or antipyretic agents. PMID:22570116

  20. 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

  1. 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.

  2. Target Selection Signals Influence Perceptual Decisions by Modulating the Onset and Rate of Evidence Accumulation.

    PubMed

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

    2016-02-22

    Computational and neurophysiological research has highlighted neural processes that accumulate sensory evidence for perceptual decisions [1]. These processes have been studied in the context of highly simplified perceptual discrimination paradigms in which the physical evidence appears at times and locations that are either entirely predictable or exogenously cued (e.g., by the onset of the stimulus itself). Yet, we are rarely afforded such certainty in everyday life. For example, when driving along a busy motorway, we must continually monitor the movements of surrounding vehicles for events that call for a lane change. In such scenarios, it is unknown which of the continuously present information sources will become relevant or when. Although it is well established that evidence integration provides an effective mechanism for countering the impact of noise [2], the question of how this mechanism is implemented in the face of uncertain evidence onsets has yet to be answered. Here, we show that when monitoring two potential sources of information for evidence occurring unpredictably in both time and space, the human brain employs discrete, early target selection signals that significantly modulate the onset and rate of neural evidence accumulation, and thereby the timing and accuracy of perceptual reports. These selection signals share many of the key characteristics of the N2pc component highlighted in the literature on visual search [3, 4] yet are present even in the absence of distractors and under situations of low temporal and spatial uncertainty. These data provide novel insights into how target selection supports decision making in uncertain environments. PMID:26853360

  3. Bridges between health care research evidence and clinical practice.

    PubMed Central

    Haynes, R B; Hayward, R S; Lomas, J

    1995-01-01

    Research is producing increasing amounts of important new evidence for health care, but there is a large gap between what this evidence shows can be done and the care that most patients actually receive. An important reason for this gap is the extensive processing that evidence requires before application. This article discusses a three-step model for bridging research evidence to management of clinical problems: getting the evidence straight, formulating evidence-based clinical policies, and applying evidence-based clinical policies at the right place and time. This model is purposely broad in scope and provides a framework for coordinating efforts to support evidence-based medical care. The authors' purpose is to represent the roles of health informatics in the context of the roles of all the key players, including health care researchers and practitioners, health care organizations, and the public. Health informatics has already made important contributions to bridging evidence to practice, including improving evidence retrieval, evaluation, and synthesis; new evidence-based information products; and computerized aids for facilitating the use of these products during clinical decision making. However, much more innovation and coordination are needed. The authors call for health informaticians to pay balanced attention to 1) the quality of evidence embodied in information innovations, 2) the performance of technologies and systems that retrieve, prepare, disseminate, and apply evidence, and 3) the fit of information tools to the specific clinical circumstances in which evidence is to be applied. Effective interdisciplinary teams that include health services researchers and other evidence experts, clinical practitioners, informaticians, and health care managers are needed to achieve success. Informaticians can make increasingly important contributions to the transfer of health care research by joining such teams. PMID:8581550

  4. 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

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

    PubMed

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

    2015-04-01

    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

  6. Demystifying "free will": the role of contextual information and evidence accumulation for predictive brain activity.

    PubMed

    Bode, Stefan; Murawski, Carsten; Soon, Chun Siong; Bode, Philipp; Stahl, Jutta; Smith, Philip L

    2014-11-01

    Novel multivariate pattern classification analyses have enabled the prediction of decision outcomes from brain activity prior to decision-makers' reported awareness. These findings are often discussed in relation to the philosophical concept of "free will". We argue that these studies demonstrate the role of unconscious processes in simple free choices, but they do not inform the philosophical debate. Moreover, these findings are difficult to relate to cognitive decision-making models, due to misleading assumptions about random choices. We review evidence suggesting that sequential-sampling models, which assume accumulation of evidence towards a decision threshold, can also be applied to free decisions. If external evidence is eliminated by the task instructions, decision-makers might use alternative, subtle contextual information as evidence, such as their choice history, that is not consciously monitored and usually concealed by the experimental design. We conclude that the investigation of neural activity patterns associated with free decisions should aim to investigate how decisions are jointly a function of internal and external contexts, rather than to resolve the philosophical "free will" debate. PMID:25452111

  7. 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

  8. Tools for Identifying Reliable Evidence and Implementing it in Everyday Clinical Care

    PubMed Central

    Cohen, Aaron M.; Demner-Fushman, Dina; Iorio, Alfonso; Sim, Ida; Smalheiser, Neil R.

    Just as translational medicine follows a long winding path from bench-to-bedside, so can Evidence-Based Medicine be envisioned as comprising a multi-step pipeline, from building evidence from raw data through synthesizing best practices and providing clinical decision support in a process described as the “evidence pyramid”. 1 At one end, a heterogeneous mix of clinical and experimental studies including clinical trials, case reports, animal models and retrospective analyses are published as new knowledge. Then, experts collect and assess high-quality relevant evidence on specific issues and publish their conclusions (e.g., regarding efficacy and safety of treatments) as systematic reviews and meta-analyses. Finally, when an expert consensus has been reached, this must reach the attention of policy makers within the profession, the government and insurance companies, resulting in new practice guidelines and altered clinical practice within hospitals and clinics. At each stage, this process requires a large investment of time and effort from many individuals with a wide range of expertise. Our panel will discuss the variety of innovative approaches that are being taken by different informatics research groups to improve each step within the evidence based medicine pipeline. These approaches are, in part, devoted to making existing data collection and synthesis practices faster and more efficient, but they also involve re-imagining and re-engineering the processes by which evidence is accumulated, evaluated and applied. PMID:24303233

  9. Desmopressin in adult urological disease: clinical evidences.

    PubMed

    Siracusano, Salvatore; Ciciliato, Stefano; Toffoli, Laura; Silvestri, Tommaso; Casotto, Daniela

    2015-01-01

    Desmopressin is a synthetic analogue of arginine vasopressin, commercially available since 1974. Desmopressin is proven effective for the treatment primary nocturnal enuresis and polyuria. It has been considered by several investigators for the treatment of nocturia with positive results and is now an established treatment for this indication. In this review, we assessed the available clinical data on desmopressin in adult urological disease. PMID:26541674

  10. 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. PMID:25938616

  11. Inhaled corticosteroids in COPD: the clinical evidence.

    PubMed

    Ernst, Pierre; Saad, Nathalie; Suissa, Samy

    2015-02-01

    In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn. The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths. Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured. PMID:25537556

  12. Toward automatic recognition of high quality clinical evidence.

    PubMed

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

    2008-01-01

    Automatic methods for recognizing topically relevant documents supported by high quality research can assist clinicians in practicing evidence-based medicine. We approach the challenge of identifying articles with high quality clinical evidence as a binary classification problem. Combining predictions from supervised machine learning methods and using deep semantic features, we achieve 73.5% precision and 67% recall. PMID:18998881

  13. 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…

  14. 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

  15. Periosteal osteosarcoma: a review of clinical evidence

    PubMed Central

    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. PMID:25784972

  16. From evidence to clinical practice in blood and marrow transplantation.

    PubMed

    Khera, Nandita

    2015-11-01

    Clinical practice in the field of blood and marrow transplantation (BMT) has evolved over time, as a result of thousands of basic and clinical research studies. While it appears that scientific discovery and adaptive clinical research may be well integrated in case of BMT, there is lack of sufficient literature to definitively understand the process of translation of evidence to practice and if it may be selective . In this review, examples from BMT and other areas of medicine are used to highlight the state of and potential barriers to evidence uptake. Strategies to help improve knowledge transfer are discussed and the role of existing framework provided by the Center for International Blood and Marrow Transplant Registry (CIBMTR) to monitor uptake and BMT Clinical Trials Network (BMT CTN) to enhance translation of evidence into practice is highlighted. PMID:25934009

  17. Clinical utility of eslicarbazepine: current evidence

    PubMed Central

    Zaccara, Gaetano; Giovannelli, Fabio; Cincotta, Massimo; Carelli, Alessia; Verrotti, Alberto

    2015-01-01

    Eslicarbazepine acetate (ESL) is a new antiepileptic drug whose mechanism of action is blockade of the voltage-gated sodium channel (VGSC). However, in respect to carbamazepine and oxcarbazepine, the active ESL metabolite (eslicarbazepine) affects slow inactivation of VGSC and has a similar affinity for the inactivated state and a lower affinity for the resting state of the channel. This new antiepileptic drug has been recently approved in Europe (trade name Zebinix) and in the United States (trade name Stedesa) for adjunctive treatment in adult subjects with partial-onset seizures, with or without secondary generalization. Following oral administration, ESL is rapidly and extensively metabolized by hepatic esterases to eslicarbazepine. This active metabolite has a linear pharmacokinetic profile, a low binding to plasma proteins (<40%), and a half-life of 20–24 hours and is mainly excreted by kidneys in an unchanged form or as glucuronide conjugates. ESL is administered once a day and has a low potential for drug–drug interactions. Efficacy and safety of this drug in patients with focal seizures have been assessed in four randomized clinical trials, and responder rates (percentage of patients with a ≥50% improvement of their seizures) ranged between 17% and 43%. Adverse events were usually mild to moderate, and the most common were dizziness, somnolence, diplopia, abnormal coordination, blurred vision, vertigo, headache, fatigue, nausea, and vomiting. ESL may be considered an interesting alternative to current antiepileptic drugs for the treatment of drug-resistant focal epilepsies. Additionally, it is under investigation in children with focal epilepsies, in patients with newly diagnosed focal epilepsies, and also in other neurological and psychiatric disorders. PMID:25709402

  18. Clinical utility of eslicarbazepine: current evidence.

    PubMed

    Zaccara, Gaetano; Giovannelli, Fabio; Cincotta, Massimo; Carelli, Alessia; Verrotti, Alberto

    2015-01-01

    Eslicarbazepine acetate (ESL) is a new antiepileptic drug whose mechanism of action is blockade of the voltage-gated sodium channel (VGSC). However, in respect to carbamazepine and oxcarbazepine, the active ESL metabolite (eslicarbazepine) affects slow inactivation of VGSC and has a similar affinity for the inactivated state and a lower affinity for the resting state of the channel. This new antiepileptic drug has been recently approved in Europe (trade name Zebinix) and in the United States (trade name Stedesa) for adjunctive treatment in adult subjects with partial-onset seizures, with or without secondary generalization. Following oral administration, ESL is rapidly and extensively metabolized by hepatic esterases to eslicarbazepine. This active metabolite has a linear pharmacokinetic profile, a low binding to plasma proteins (<40%), and a half-life of 20-24 hours and is mainly excreted by kidneys in an unchanged form or as glucuronide conjugates. ESL is administered once a day and has a low potential for drug-drug interactions. Efficacy and safety of this drug in patients with focal seizures have been assessed in four randomized clinical trials, and responder rates (percentage of patients with a ≥50% improvement of their seizures) ranged between 17% and 43%. Adverse events were usually mild to moderate, and the most common were dizziness, somnolence, diplopia, abnormal coordination, blurred vision, vertigo, headache, fatigue, nausea, and vomiting. ESL may be considered an interesting alternative to current antiepileptic drugs for the treatment of drug-resistant focal epilepsies. Additionally, it is under investigation in children with focal epilepsies, in patients with newly diagnosed focal epilepsies, and also in other neurological and psychiatric disorders. PMID:25709402

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

    NASA Astrophysics Data System (ADS)

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

    1993-09-01

    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.

  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. 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. PMID:22362829

  2. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis

    PubMed Central

    Kaltwasser, J; Werner, E; Schalk, K; Hansen, C; Gottschalk, R; Seidl, C

    1998-01-01

    Background—Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. 
Aims—To investigate this effect in patients with genetic haemochromatosis, and, more importantly, the effect of regular tea drinking on the accumulation of storage iron in these patients over one year. 
Patients—Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, they were separated into a group instructed to drink a particularly tannin rich tea regularly with meals and a control group. 
Methods—Intestinal iron absorption from a test meal was measured using whole body counting. Body iron stores were evaluated quantitatively by exhaustive phlebotomy, using haemoglobin, saturation of serum iron binding capacity, and serum ferritin for the assessment of body iron status. 
Results—A significant reduction in iron absorption was observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one third compared with that of the control group. 
Conclusions—Regular tea drinking with meals reduces the frequency of phlebotomies required in the management of patients with haemochromatosis. 

 Keywords: genetic haemochromatosis; iron absorption; tea; storage iron accumulation PMID:9824354

  3. Evidence based dental care: integrating clinical expertise with systematic research.

    PubMed

    Kishore, Mallika; Panat, Sunil R; Aggarwal, Ashish; Agarwal, Nupur; Upadhyay, Nitin; Alok, Abhijeet

    2014-02-01

    Clinical dentistry is becoming increasingly complex and our patients more knowledgeable. Evidence-based care is now regarded as the "gold standard" in health care delivery worldwide. The basis of evidence based dentistry is the published reports of research projects. They are, brought together and analyzed systematically in meta analysis, the source for evidence based decisions. Activities in the field of evidence-based dentistry has increased tremendously in the 21(st) century, more and more practitioners are joining the train, more education on the subject is being provided to elucidate the knotty areas and there is increasing advocacy for the emergence of the field into a specialty discipline. Evidence-Based Dentistry (EBD), if endorsed by the dental profession, including the research community, may well- influence the extent to which society values dental research. Hence, dental researchers should understand the precepts of EBD, and should also recognize the challenges it presents to the research community to strengthen the available evidence and improve the processes of summarizing the evidence and translating it into practice This paper examines the concept of evidence-based dentistry (EBD), including some of the barriers and will discuss about clinical practice guidelines. PMID:24701551

  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. Therapy of nephrolithiasis: where is the evidence from clinical trials?

    PubMed

    Pachaly, Maria Aparecida; Baena, Cristina Pellegrino; Carvalho, Mauricio de

    2016-03-01

    The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis. PMID:27049371

  6. Evidence recognition and collection in the clinical setting.

    PubMed

    Hoyt, C A

    1999-05-01

    The critical care nurse encounters victims of violence and abuse in the clinical setting. From these patients or from their visitors, evidence can be collected that, when used in legal proceedings, may interrupt the cycle of violence if a perpetrator is identified and found guilty by a court of law. Evidence may be tangible or intangible, and includes what one hears, smells, sees, and touches. This article discusses proper evidence recognition, collection, and preservation. With an understanding of proper forensic techniques, the critical care nurse can be an outstanding patient advocate. PMID:10646460

  7. [Evidence-based clinical practice. Part II--Searching evidence databases].

    PubMed

    Bernardo, Wanderley Marques; Nobre, Moacyr Roberto Cuce; Jatene, Fábio Biscegli

    2004-01-01

    The inadequacy of most of traditional sources for medical information, like textbook and review article, do not sustained the clinical decision based on the best evidence current available, exposing the patient to a unnecessary risk. Although not integrated around clinical problem areas in the convenient way of textbooks, current best evidence from specific studies of clinical problems can be found in an increasing number of Internet and electronic databases. The sources that have already undergone rigorous critical appraisal are classified as secondary information sources, others that provide access to original article or abstract, as primary information source, where the quality assessment of the article rely on the clinician oneself . The most useful primary information source are SciELO, the online collection of Brazilian scientific journals, and Medline, the most comprehensive database of the USA National Library of Medicine, where the search may start with use of keywords, that were obtained at the structured answer construction (P.I.C.O.), with the addition of boolean operators "AND", "OR", "NOT". Between the secondary information sources, some of them provide critically appraised articles, like ACP Journal Club, Evidence Based Medicine and InfoPOEMs, others provide evidences organized as online texts, such as "Clinical Evidence" and "UpToDate", and finally, Cochrane Library are composed by systematic reviews of randomized controlled trials. To get studies that could answer the clinical question is part of a mindful practice, that is, becoming quicker and quicker and dynamic with the use of PDAs, Palmtops and Notebooks. PMID:15253037

  8. 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

  9. A commentary on randomized clinical trials: How to produce them with a good level of evidence

    PubMed Central

    Flecha, Olga Dumont; Douglas de Oliveira, Dhelfeson Willya; Marques, Leandro Silva; Gonçalves, Patricia Furtado

    2016-01-01

    Randomized clinical trial (RCT) is the gold standard study for the evaluation of health interventions and is considered the second level of evidence for clinical decision making. However, the quality of the evidence produced by these studies is dependent on the methodological rigor employed at every stage of their execution. The purpose of randomization is to create groups that are comparable independent of any known or unknown potential confounding factor. A critical evaluation of the literature reveals that, for many years, RCTs have been developed based on inaccurate methodological criteria, and empirical evidence began to accumulate. Thus, guidelines were developed to assist authors, reviewers, and editors in the task of developing and assessing the methodological consistency of this type of study. The objective of this article is to review key aspects to design a good-quality RCT, supporting the scientific community in the production of reliable evidence and favoring clinical decision making to allow the patient to receive the best health care. PMID:27141473

  10. Does maggot therapy promote wound healing? The clinical and cellular evidence.

    PubMed

    Nigam, Y; Morgan, C

    2016-05-01

    The larvae of Lucillia sericata, or maggots of the green-bottle fly, are used worldwide to help debride chronic, necrotic and infected wounds. Whilst there is abundant clinical and scientific evidence to support the role of maggots for debriding and disinfecting wounds, not so much emphasis has been placed on their role in stimulating wound healing. However, there is accumulating evidence to suggest that maggots and their externalized secretions may also promote wound healing in stubborn, recalcitrant chronic ulcers. There are a growing number of clinical reports which support the observation that wounds which have been exposed to a course of maggot debridement therapy also show earlier healing and closure end-points. In addition, recent pre-clinical laboratory studies also indicate that maggot secretions can promote important cellular processes which explain this increased healing activity. Such processes include activation of fibroblast migration, angiogenesis (the formation of new blood vessels from pre-existing vessels) within the wound bed, and an enhanced production of growth factors within the wound environment. Thus, in this review, we summarize the clinical evidence which links maggots and improved wound healing, and we précis recent scientific studies which examine and identify the role of maggots, particularly individual components of maggot secretions, on specific cellular aspects of wound healing. PMID:26691053

  11. 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.

  12. EVIDENCE AND CLINICAL DECISIONS: Asking the Right Questions to Obtain Clinically Useful Answers

    PubMed Central

    Proffit, William R.

    2013-01-01

    Orthodontists need to know the effectiveness, efficiency and predictability of treatment approaches and methods, which can be learned only by carefully studying and evaluating treatment outcomes. The best data for outcomes come from randomized clinical trials (RCTs), but retrospective data can provide satisfactory evidence if the subjects were a well-defined patient group, all the patients were accounted for, and the percentages of patients with various possible outcomes are presented along with measures of the central tendency and variation. Meta-analysis of multiple RCTs done in a similar way and systematic reviews of the literature can strengthen clinically-useful evidence, but reviews that are too broadly based are more likely to blur than clarify the information clinicians need. Reviews that are tightly focused on seeking the answer to specific clinical questions and evaluating the quality of the evidence available to answer the question are much more likely to provide clinically useful data. PMID:24198455

  13. Evidence-based clinical practice for the neurointerventionalist.

    PubMed

    Hirsch, Joshua A; Turk, Aquilla S; Mocco, J; Fiorella, David J; Jayaraman, Mahesh V; Meyers, Phillip M; Yoo, Albert J; Manchikanti, Laxmaiah

    2015-03-01

    The field of neurointerventional (NI) surgery has developed in the context of technologic innovation. Many treatments readily provided in 2014 would have been hard to imagine as recently as 10 years ago. The reality of present day NI care is that, while providers, payors, policy makers and patients rely on evidence to guide NI decision-making, the available data are often less robust than participants might desire. In this paper we will explore the fundamentals of evidence-based clinical practice. PMID:24578482

  14. 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. PMID:25174902

  15. 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.

  16. Hypericum for depression. An update of the clinical evidence.

    PubMed

    Stevinson, C; Ernst, E

    1999-12-01

    This review is aimed at providing an updated evaluation of the clinical evidence regarding Hypericum perforatum (St. John's wort) as an antidepressant, based on recently published randomised controlled trials. Computerised literature searches revealed six trials published since the metaanalysis by Linde et al. (1996) [Linde, K., Ramirez, G., Mulrow, C.D., Pauls, A., Weidenhammer, W., Melchart, D., 1996. St. John's wort for depression--an overview and meta-analysis of randomised clinical trials. Br. Med. J. 313, 253-258]. The results of these studies provide further evidence that hypericum is superior to placebo in treating mild or moderate depression. However, there is still insufficient evidence to assess the efficacy of hypericum in comparison with conventional, particularly modern, antidepressants. Furthermore, there remains a lack of trials assessing long-term effects, other types of depression and different preparations and doses. It is concluded that recent clinical trials strengthen the case for hypericum as an antidepressant, but more work needs to be done to answer the remaining questions. PMID:10625118

  17. 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

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

    PubMed

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

    2015-01-01

    This comprehensive review critically evaluates whether supposed health benefits propounded upon human consumption of conjugated linoleic acids (CLAs) are clinically proven or not. With a general introduction on the chemistry of CLA, major clinical evidences pertaining to intervention strategies, body composition, cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated. Supposed adverse effects such as oxidative stress, insulin resistance, irritation of intestinal tract and milk fat depression are also examined. It seems that no consistent result was observed even in similar studies conducted at different laboratories, this may be due to variations in age, gender, racial and geographical disparities, coupled with type and dose of CLA supplemented. Thus, supposed promising results reported in mechanistic and pre-clinical studies cannot be extrapolated with humans, mainly due to the lack of inconsistency in analyses, prolonged intervention studies, follow-up studies and international co-ordination of concerted studies. Briefly, clinical evidences accumulated thus far show that CLA is not eliciting significantly promising and consistent health effects so as to uphold it as neither a functional nor a medical food. PMID:25972911

  19. Evidence of clinical competence by simulation, a hermeneutical observational study.

    PubMed

    Lejonqvist, Gun-Britt; Eriksson, Katie; Meretoja, Riitta

    2016-03-01

    Making the transition from theory to practise easier in nursing education through simulation is widely implemented all over the world, and there is research evidence of the positive effects of simulation. The pre-understanding for this study is based on a definition of clinical competence as encountering, knowing, performing, maturing and developing, and the hypothesis is that these categories should appear in simulated situations. The aim of the study was to explore the forms and expressions of clinical competence in simulated situations and furthermore to explore if and how clinical competence could be developed by simulation. An observational hermeneutic study with a hypothetic-deductive approach was used in 18 simulated situations with 39 bachelor degree nursing students. In the situations, the scenarios, the actors and the plots were described. The story told was "the way from suffering to health" in which three main plots emerged. The first was, doing as performing and knowing, which took the shape of knowing what to do, acting responsibly, using evidence and equipment, appearing confident and feeling comfortable, and sharing work and information with others. The second was, being as encountering the patient, which took the shape of being there for him/her and confirming by listening and answering. The third plot was becoming as maturing and developing which took the shape of learning in co-operation with other students. All the deductive categories, shapes and expressions appeared as dialectic patterns having their negative counterparts. The study showed that clinical competence can be made evident and developed by simulation and that the challenge is in encountering the patient and his/her suffering. PMID:26763209

  20. 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. PMID:18952929

  1. 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

  2. Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use.

    PubMed

    Saadi, Mohammed; McCallum, Richard W

    2013-03-01

    Irritable bowel syndrome (IBS) is the most common functional bowel disease that affects up to 15% of the US population. The majority of patients with IBS have significant bloating and gas. Recent evidence is beginning to suggest that patients with IBS may have an alteration in the gastrointestinal flora. Specifically, findings suggest that patients with IBS have excessive bacteria in the small bowel, referred to as bacterial overgrowth. Therefore there may be benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable antibiotic that demonstrates no clinically relevant bacterial resistance. Some studies have demonstrated the efficacy and durable improvement of IBS symptoms after treatment with rifaximin. In this review we explore the current data showing the association of small intestinal bacterial overgrowth (SIBO) and IBS as well as review the available data on the clinical use of rifaximin in the treatment of SIBO in patients with IBS. PMID:23556126

  3. Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use

    PubMed Central

    Saadi, Mohammed

    2013-01-01

    Irritable bowel syndrome (IBS) is the most common functional bowel disease that affects up to 15% of the US population. The majority of patients with IBS have significant bloating and gas. Recent evidence is beginning to suggest that patients with IBS may have an alteration in the gastrointestinal flora. Specifically, findings suggest that patients with IBS have excessive bacteria in the small bowel, referred to as bacterial overgrowth. Therefore there may be benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable antibiotic that demonstrates no clinically relevant bacterial resistance. Some studies have demonstrated the efficacy and durable improvement of IBS symptoms after treatment with rifaximin. In this review we explore the current data showing the association of small intestinal bacterial overgrowth (SIBO) and IBS as well as review the available data on the clinical use of rifaximin in the treatment of SIBO in patients with IBS. PMID:23556126

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways. PMID:26521074

  6. 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. PMID:26725837

  7. 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

  8. Clinical intuition versus statistics: different modes of tacit knowledge in clinical epidemiology and evidence-based medicine.

    PubMed

    Braude, Hillel D

    2009-01-01

    Despite its phenomenal success since its inception in the early nineteen-nineties, the evidence-based medicine movement has not succeeded in shaking off an epistemological critique derived from the experiential or tacit dimensions of clinical reasoning about particular individuals. This critique claims that the evidence-based medicine model does not take account of tacit knowing as developed by the philosopher Michael Polanyi. However, the epistemology of evidence-based medicine is premised on the elimination of the tacit dimension from clinical judgment. This is demonstrated through analyzing the dichotomy between clinical and statistical intuition in evidence-based medicine's epistemology of clinical reasoning. I argue that clinical epidemiology presents a more nuanced epistemological model for the application of statistical epidemiology to the clinical context. Polanyi's theory of tacit knowing is compatible with the model of clinical reasoning associated with clinical epidemiology, but not evidence-based medicine. PMID:19548116

  9. The Nitrogen Legacy: Evidence of Soil Nitrogen Accumulation in Anthropogenic Landscapes

    NASA Astrophysics Data System (ADS)

    Van Meter, K. J.; Basu, N. B.

    2013-12-01

    Human modification of the nitrogen (N) cycle has resulted in increased flows of reactive N, with some suggesting that planetary boundaries for maintaining human and ecosystem health have been exceeded. Persistence of large hypoxic zones in inland and coastal waters created by elevated concentrations of nitrate is one of the most significant impacts of such increased flows. While the need to manage these flows and their associated ecological impacts is recognized, best management practices to reduce stream N concentrations have had only limited success. Some have attributed this lack of success to an accumulation of legacy N stores from decades of fertilizer application. Nitrogen mass balance studies seem to suggest an ongoing retention of N within anthropogenic landscapes, but the exact form and location of this legacy N and the associated retention rates are subject to question. Here we introduce an unprecedented analysis of long-term soil data from the Mississippi River Basin (MRB) revealing significant increases in total N (TN) content. We show that TN accumulation for the MRB accounts for 49% of net anthropogenic N inputs (NANI), which complements previous work indicating that approximately 25% of net inputs are lost as riverine output. These findings significantly reduce the uncertainty associated with basin-level N retention. Further, our results demonstrate that, despite conventional wisdom of intensive agriculture leading to a depletion of TN, an accumulation of N is occurring in the deeper subsurface (25 - 100 cm) that compensates for depletion in the plow layer (0-25 cm). These legacy N stores may lead to time lags between changes in management practices and decreasing N concentrations in stream waters, thus resulting in multidecadal effects on water quality in agricultural watersheds.

  10. 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. PMID:27245104

  11. Evidence for the Accumulation of Peroxidized Lipids in Membranes of Senescing Cotyledons 1

    PubMed Central

    Pauls, K. Peter; Thompson, John E.

    1984-01-01

    Fluorescent products of lipid peroxidation accumulate with age in microsomal membranes from senescing cotyledons of Phaseolus vulgaris. The temporal pattern of accumulation is closely correlated with a rise in the lipid phase transition temperature reflecting the formation of gel phase lipid. Increased levels of fluorescent peroxidation products are also detectable in total lipid extracts of senescent cotyledons. Lipoxygenase activity increases with advancing age by about 3-fold on a fresh weight basis and 4-fold on a dry weight basis indicating that the tissue acquires elevated levels of lipid hydroperoxides. As well, levels of glutathione and superoxide dismutase activity decline on a dry weight basis as the cotyledons age, rendering the tissue more susceptible to oxidative damage. Catalase activity rises initially and then declines during senescence, but peroxidase activity rises steeply. Thus, apart from this increase in peroxidase, which would scavenge H2O2 only if appropriate cosubstrates were available, the defense mechanisms for coping with activated oxygen species (O2−, H2O2, OH) are less effective in the older tissue. The observations support the contention that formation of gel phase lipid in senescing membranes is attributable to lipid peroxidation and suggest that the reactions of lipid peroxidation are utilized by the cotyledons to mediate deteriorative changes accompanying the mobilization and transport of metabolites from the storage tissue to the developing embryo. Images Fig. 10 PMID:16663749

  12. Current evidence on atypical odontalgia: diagnosis and clinical management.

    PubMed

    Abiko, Yoshihiro; Matsuoka, Hirofumi; Chiba, Itsuo; Toyofuku, Akira

    2012-01-01

    Patients with atypical odontalgia (AO) complain of medically unexplained toothache. No evidence-based diagnostic criteria or treatment guidelines are yet available. The present paper addresses seven clinical questions about AO based on current knowledge in the literature and discusses diagnostic criteria and guidelines for treatment and management. The questions are (i) What is the prevalence of AO in the community? (ii) What psychological problems are experienced by patients with AO? (iii) Are there any comorbidities of AO? (iv) Is local anesthesia effective for the relief of pain in AO? (v) Are there any characteristic symptoms of AO other than spontaneous pain? (vi) Are antidepressants effective for treatment of AO? (vii) Are anticonvulsants effective for treatment of AO? Our literature search provided answers for these questions; however, there is insufficient evidence-based data to establish guidelines for the diagnosis and treatment of AO. Overall, some diagnostic criteria for neuropathic pain and persistent dentoalveolar pain disorder may be applied to AO patients. The patient's psychogenic background should always be considered in the treatment and/or management of AO. The clinicians may need to treat AO patients using Patient-Oriented Evidence that Matters approach. PMID:22844283

  13. Gastric cancer stem cells: evidence, potential markers, and clinical implications.

    PubMed

    Brungs, Daniel; Aghmesheh, Morteza; Vine, Kara L; Becker, Therese M; Carolan, Martin G; Ranson, Marie

    2016-04-01

    Gastric cancer is a significant global health problem. It is the fifth most common cancer and third leading cause of cancer-related death worldwide (Torre et al. in CA Cancer J Clin 65(2):87-108, 2015). Despite advances in treatment, overall prognosis remains poor, due to tumour relapse and metastasis. There is an urgent need for novel therapeutic approaches to improve clinical outcomes in gastric cancer. The cancer stem cell (CSC) model has been proposed to explain the high rate of relapse and subsequent resistance of cancer to current systemic treatments (Vermeulen et al. in Lancet Oncol 13(2):e83-e89, 2012). CSCs have been identified in many solid malignancies, including gastric cancer, and have significant clinical implications, as targeting the CSC population may be essential in preventing the recurrence and spread of a tumour (Dewi et al. in J Gastroenterol 46(10):1145-1157, 2011). This review seeks to summarise the current evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers, clinical implications, and potential therapeutic approaches. PMID:26428661

  14. Lifespan mercury accumulation pattern in Liza aurata : Evidence from two southern European estuaries

    NASA Astrophysics Data System (ADS)

    Tavares, S.; Oliveira, H.; Coelho, J. P.; Pereira, M. E.; Duarte, A. C.; Pardal, M. A.

    2011-10-01

    Mercury accumulation throughout the lifespan of Liza aurata (Risso, 1810) was analysed in four tissues (muscle, gills, liver and brain) in two southern European coastal ecosystems with distinct mercury contamination. Specimens from four to five age classes were captured in two sampling sites in the Ria de Aveiro (Laranjo bay and Mira), a system historically contaminated by industrial mercury, and in one site in the Mondego estuary, assumed as a mercury-free ecosystem. Mercury concentration in all tissues was found to be significantly higher in the Ria de Aveiro (Laranjo bay) compared to the Mondego, in accordance with the environmental contamination (water, sediments and suspended particulate matter). Significant differences inside the Ria de Aveiro (between the Mira and Laranjo bay) were only detected in the liver. This tissue registered the highest levels of mercury (ranging from 0.11 to 4.2 μg g -1 ) in all sampling sites, followed by muscle, brain, and gills. In all sampling sites and tissues was denoted a mercury dilution pattern along the lifecycle (except in liver at the Mondego, the reference area where the concentrations are always very low). An exponential trend was found in the metal age variation patterns in Laranjo (the most contaminated area) and a linear trend in the Mira and the Mondego (the least contaminated areas). Organic mercury concentration in muscle generally accounted for over 95% of total mercury concentration, and followed the same accumulation pattern of total mercury. This fish species is of lesser importance in mercury transfer to adjacent coastal areas and although the consumption of fish from Laranjo may present some risk for the humans, this risk decreases with fish age/size.

  15. 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

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

    PubMed

    Wright, Stephen

    2007-08-01

    Whereas the cannabis plant has a long history of medicinal use, it is only in recent years that a sufficient understanding of the pharmacology of the main plant constituents has allowed for a better understanding of the most rational therapeutic targets. The distribution of cannabinoid receptors, both within the nervous system and without, and the development of pharmacological tools to investigate their function has lead to a substantial increase in efforts to develop cannabinoids as therapeutic agents. Concomitant with these efforts, the understanding of the pharmacology of plant cannabinoids at receptor and other systems distinct from the cannabinoid receptors suggests that the therapeutic applications of plant-derived cannabinoids (and presumably their synthetic derivatives also) may be diverse. This review aims to discuss the clinical evidence investigating the use of medicines derived, directly or indirectly, from plant cannabinoids with special reference to neurological disorders. Published studies suggest that the oral administration of cannabinoids may not be the preferred route of administration and that plant extracts show greater evidence of efficacy than synthetic compounds. One of these, Sativex (GW Pharmaceuticals), was approved as a prescription medicine in Canada in 2005 and is currently under regulatory review in the EU. PMID:17952657

  17. Probiotics and Gastrointestinal Disease: Clinical Evidence and Basic Science

    PubMed Central

    Petrof, Elaine O.

    2010-01-01

    Our intestinal microbiota serve many roles vital to the normal daily function of the human gastrointestinal tract. Many probiotics are derived from our intestinal bacteria, and have been shown to provide clinical benefit in a variety of gastrointestinal conditions. Current evidence indicates that probiotic effects are strain-specific, they do not act through the same mechanisms, and nor are all probiotics indicated for the same health conditions. However, they do share several common features in that they exert anti-inflammatory effects, they employ different strategies to antagonize competing microorganisms, and they induce cytoprotective changes in the host either through enhancement of barrier function, or through the upregulation of cytoprotective host proteins. In this review we focus on a few selected probiotics – a bacterial mixture (VSL#3), a Gram-negative probiotic (E. coli Nissle 1917), two Gram-positive probiotic bacteria (LGG, L. reuteri), and a yeast probiotic (S. boulardii) – for which sound clinical and mechanistic data is available. Safety of probiotic formulations is also discussed. PMID:20890386

  18. Heterogeneity of major affective disorders. Biological and clinical evidence.

    PubMed

    Vita, A; Sacchetti, E; Conte, G; Alciati, A; Pennati, A

    1985-01-01

    In this paper we summarize the results of our recent and present research focused on analyzing the correlations between neurochemical, pharmacological and clinical parameters in patients with Major Depression. There is evidence that: a) pretreatment urinary MHPG is a useful predictor for clinical response to tricyclic antidepressants and to long-term lithium treatment; b) urinary MHPG is positively correlated to the age at onset of the disease; c) previous responses to tricyclics and age at onset of affective illness are supplementary tools for predicting the effectiveness of lithium and antidepressant drugs; d) platelet alpha-2-adrenoceptor density is inversely correlated with both urinary MHPG and age at onset; e) cerebral ventricular size is positively correlated with urinary MHPG and age at onset and may discriminate between patients with different outcomes on lithium prophylaxis; f) low MHPG excretors are more likely to have suffered from stressful life events in early childhood than normal-to-high excretors. Taken together, these results lend strong support to the hypothesis that Major Affective Disorder is a heterogeneous illness and that inherently different subgroups of affective patients can be recognized. PMID:2990848

  19. A Review of Nebivolol Pharmacology and Clinical Evidence.

    PubMed

    Fongemie, Justin; Felix-Getzik, Erika

    2015-08-01

    Nebivolol is a highly selective β1-adrenergic receptor antagonist with a pharmacologic profile that differs from those of other drugs in its class. In addition to cardioselectivity mediated via β1 receptor blockade, nebivolol induces nitric oxide-mediated vasodilation by stimulating endothelial nitric oxide synthase via β3 agonism. This vasodilatory mechanism is distinct from those of other vasodilatory β-blockers (carvedilol, labetalol), which are mediated via α-adrenergic receptor blockade. Nebivolol is approved for the treatment of hypertension in the US, and for hypertension and heart failure in Europe. While β-blockers are not recommended within the current US guidelines as first-line therapy for treatment of essential hypertension, nebivolol has shown comparable efficacy to currently recommended therapies in lowering peripheral blood pressure in adults with hypertension with a very low rate of side effects. Nebivolol also has beneficial effects on central blood pressure compared with other β-blockers. Clinical data also suggest that nebivolol may be useful in patients who have experienced erectile dysfunction while on other β-blockers. Here we review the pharmacological profile of nebivolol, the clinical evidence supporting its use in hypertension as monotherapy, add-on, and combination therapy, and the data demonstrating its positive effects on heart failure and endothelial dysfunction. PMID:26177892

  20. 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. PMID:21268673

  1. Evidence for accumulated melt beneath the slow-spreading Mid-Atlantic Ridge

    NASA Astrophysics Data System (ADS)

    Sinha, M. C.; Navin, D. A.; MacGregor, L. M.; Constable, S.; Peirce, C.; White, A.; Heinson, G.; Inglis, M. A.

    The analysis of data from a multi-component geophysical experiment conducted on a segment of the slow-spreading (20 mm yr-1) Mid-Atlantic Ridge shows compelling evidence for a significant crustal magma body beneath the ridge axis. The role played by a crustal magma chamber beneath the axis in determining both the chemical and physical architecture of the newly formed crust is fundamental to our understanding of the accretion of oceanic lithosphere at spreading ridges, and over the last decade subsurface geophysical techniques have successfully imaged such magma chambers beneath a number of intermediate and fast spreading (60-140 mm yr-1 full rate) ridges. However, many similar geophysical studies of slow-spreading ridges have, to date, found little or no evidence for such a magma chamber beneath them. The experiment described here was carefully targeted on a magmatically active, axial volcanic ridge (AVR) segment of the Reykjanes Ridge, centred on 57 degrees 43 minutes North. It consisted of four major components: wide-angle seismic profiles using ocean bottom seismometers; seismic reflection profiles; controlled source electromagnetic sounding; and magneto-telluric sounding. Interpretation and modelling of the first three of these datasets shows that an anomalous body lies at a depth of between 2 and 3 km below the seafloor beneath the axis of the AVR. This body is characterized by anomalously low seismic P-wave velocity and electrical resistivity, and is associated with a seismic reflector. The geometry and extent of this melt body shows a number of similarities with the axial magma chambers observed beneath ridges spreading at much higher spreading rates. Magneto-telluric soundings confirm the existence of very low electrical resistivities in the crust beneath the AVR and also indicate a deeper zone of low resistivity within the upper mantle beneath the ridge.

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

    PubMed Central

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

    2016-01-01

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

  3. Arbor Clinical Nutrition Updates: evidence-based clinical nutrition education using the Internet.

    PubMed

    Helman, A D

    2005-08-01

    The Arbor Clinical Nutrition Updates (ACNU) is a weekly electronic nutrition journal for health professionals. Each issue summarises several recent clinical research papers appearing in the general medical and nutrition literature and which deal with a common nutrition topic. A commentary is added on how this research fits in with previous work, and what it all means for the practising clinician. ACNU is the world's most widely read electronic nutrition publication, with over 100,000 largely health-professional readers in 186 countries. It is published in nine languages and distributed by email without charge in both plain text and Acrobat formats. ACNU utilises a number of the Internet's unique characteristics to facilitate broad reach, currency and active reader feedback. This, together with its brevity and summarising format, helps to maintain its relevance to the nutrition education needs of health professionals, particularly those in clinical practice, and to overcome the factors most commonly reported by health professionals as obstacles to their greater adoption of evidence-based medicine. ACNU is intended to be a collaboration with the primary research journals to extend the reach of new nutrition research findings to a wider community of researchers, academics and clinicians than each journal might otherwise reach individually. As such, ACNU utilises the Internet to promote the goals of open-access publishing and evidence-based medicine. PMID:16052179

  4. Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

    PubMed Central

    Morris, C D; Rose, A; Curwen, J; Hughes, A M; Wilson, D J; Webb, D J

    2005-01-01

    Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy. PMID:15956965

  5. Target blood pressure in diabetes patients with hypertension--what is the accumulated evidence in 2011?

    PubMed

    Nilsson, Peter M

    2011-08-01

    There is overwhelming evidence that hypertension is an important risk factor for both macrovascular and microvascular complications in patients with diabetes, but the problem remains to identify appropriate goals for preventive therapies. A number of guidelines (the European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) 2007, the Joint National Committee (JNC)-VII 2003, the American Diabetes Association (ADA) 2011) have for example advocated a blood pressure goal of less than 130/80 mmHg, but this suggestion has been challenged by findings in recent trials and meta-analyses (2011). The European Society of Hypertension (ESH) therefore recommends a systolic blood pressure goal of "well below" 140 mmHg. Based on evidence from both randomized controlled trials (hypertension optimal treatment (HOT), action in diabetes and vascular disease: preterax and diamicron MR controlled evaluation (ADVANCE), action to control cardiovascular risk in diabetes (ACCORD)) and observational studies (ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET), international verapamil-trandolapril study (INVEST), treat to new targets (TNT), and the National Diabetes Register (NDR)), it has been shown that the benefit for stroke reduction remains even at lower achieved blood pressure levels, but the risk of coronary events may be uninfluenced or even increased at lower systolic blood pressure levels. In a recent meta-analysis, it was therefore concluded that the new recommended goal should be 130-135 mmHg systolic blood pressure for most patients with type 2 diabetes. Other risk factors should also be controlled with a more ambitious strategy applied in the younger patients with shorter diabetes duration, but a more cautious approach in the elderly and frail patients with a number of vascular or non-vascular co-morbidities. In patients from East Asia, such as China, the stroke risk is relatively higher than the risk of

  6. 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

  7. 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

  8. 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. PMID:25729555

  9. Evolution of subgroup A respiratory syncytial virus: evidence for progressive accumulation of amino acid changes in the attachment protein.

    PubMed Central

    Cane, P A; Pringle, C R

    1995-01-01

    The variability of the attachment (G) proteins of 48 subgroup A isolates of respiratory syncytial virus (RSV) isolated over 38 years has been examined. Nucleotide sequences of two variable regions of the G protein genes were determined following amplification by PCR. The isolates showed temporal rather than geographical clustering, and there was evidence for progressive accumulation of amino acid changes at an average rate of approximately 0.25% per year estimated over the entire protein. The cocirculation of lineages of RSV at present appears to be the result of a process of evolution and survival of particular genotypes and the extinction of others. Analysis of reactivity of the isolates with monoclonal antibodies showed that their antigenic profiles closely paralleled their relatedness by nucleotide sequence, suggesting that antigenic drift due to immune selection may be occurring. PMID:7707517

  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. Evidence-Based Practice for Outpatient Clinical Teams

    ERIC Educational Resources Information Center

    Hamilton, John D.

    2006-01-01

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

  12. 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

  13. 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. PMID:27160381

  14. 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

  15. [Explanation of Evidence-based Guidelines of Clinical Practice with Acupuncture and Moxibustion: Adult Bronchial Asthma].

    PubMed

    Jiao, Yue; Wu, Zhongchao; Zhou, Wenna; Si, Xiaohua; Wang, Jingjing; Zhou, Jincao; Chen, Zhongjie; Li, Rongjun; Zhao, Xiaoguang; Xiao, Liwei

    2016-05-01

    The development and compilation of Evidence-based Guidelines of Clinical Practice with Acupuncture and Moxibustion: Adult Bronchial Asthma are introduced from three aspects, named the guideline methodology, the guideline structure and the guideline content. Based on the acupuncture-moxibustion practice and clinical research, the evidence-based medicine method is adopted. During the development and compilation of the guideline, the characteristics and advantages of acupuncture and moxibustion are specially considered in the treatment of this disease; the latest optimum evidences at home and abroad, experts' experience and patients' value are closely integrated with each other. Additionally, the worldwide accepted assessments of evidence quality and the recommendation (GRADE system) are combined with the clinical evidences of the ancient and modern famous acupuncture-moxibustion experts, and the clinical research evidences are with the experts' consensus to the large extent. The purpose of the guideline is to provide the maximal guidance to the clinical physicians. PMID:27509620

  16. [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

  17. 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. PMID:26724512

  18. Clinically assisted hydration and the Liverpool Care Pathway: Catholic ethics and clinical evidence.

    PubMed

    Nowarska, Anna

    2015-08-01

    The Liverpool Care Pathway for the Dying Patient (LCP), a framework introduced for providing comfortable care at the last stage of life, has recently become highly contentious. Among the most serious allegations levelled against it, has been that the LCP may be used as a covert form of euthanasia by withdrawal of clinically assisted hydration (CAH). This concern has been raised, in particular by a number of Catholic medical professionals, who have asserted that the LCP is incompatible with Catholic ethics. This paper examines the key Catholic ethical principles relevant to treatment and care towards the end of life (the sanctity/inviolability of life principle, the distinction between ordinary and extraordinary means). Relevant current clinical evidence regarding CAH in relation to terminal thirst, dehydration, prolongation of life and possible negative impacts on the dying is also scrutinised. It is argued that for some patients at the very end of life it may be permissible and even desirable to withhold or withdraw it. Thus, as administration of CAH may become extraordinary, forgoing it in some situations is fully compatible with Catholic ethics. The article therefore concludes that the stance of the LCP in respect of provision of CAH is fully in alignment with Catholic teaching. PMID:25034970

  19. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  20. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of...

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

    ERIC Educational Resources Information Center

    Muttiah, Nimisha; Georges, Katie; Brackenbury, Tim

    2011-01-01

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

  2. Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

    PubMed Central

    Bejaimal, Shayna AD; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

    2013-01-01

    Background Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. Objective To compare the performance of searches in PubMed and Google Scholar. Methods We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Results Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). Conclusions For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles. PMID:23948488

  3. Activity in Inferior Parietal and Medial Prefrontal Cortex Signals the Accumulation of Evidence in a Probability Learning Task

    PubMed Central

    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. PMID:23401673

  4. [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. PMID:25464952

  5. Exploring the methodology and application of clinical pathway in evidence-based Chinese medicine.

    PubMed

    Wang, Sicheng; Yu, He; Liu, Jianping; Liu, Baoyan

    2011-06-01

    At present, clinical pathway has become one of the most important health care reform measures in many countries. In this study, the authors introduced basic concepts and explored the application of the clinical pathway of evidence-based Chinese medicine incorporated with the methodology from the concepts of management, evidence-based medicine, operational research and health economics. Such concepts provide examples and experiences, on which the application of clinical pathway in Chinese medicine practice in China can be based. PMID:21695620

  6. Examining the evidence for the use of probiotics in clinical practice.

    PubMed

    Hickson, Mary

    This article reviews the use of probiotics in clinical practice, including explanations of what they are and how they work. Evidence for the health benefits of consuming probiotic bacteria and yeast are examined in several clinical conditions. The problems associated with making recommendations for the use of probiotics in clinical practice are also discussed. PMID:23634499

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

    PubMed Central

    2013-01-01

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

  8. Nephrotic syndrome in dogs: clinical features and evidence-based treatment considerations.

    PubMed

    Klosterman, Emily S; Pressler, Barrak M

    2011-08-01

    Nephrotic syndrome (NS), defined as the concurrent presence of hypoalbuminemia, proteinuria, hyperlipidemia, and fluid accumulation in interstitial spaces and/or body cavities, is a rare complication of glomerular disease in dogs, cats, and people. Affected animals frequently have markedly abnormal urine protein:creatinine ratios because of urinary loss of large amounts of protein; however, hypoalbuminemia-associated decreased plasma oncotic pressure is insufficient to explain fluid extravasation in most laboratory models, and, instead, either aberrant renal tubule retention of sodium with resultant increase in hydrostatic pressure or a systemic increase in vascular permeability may be the primary defects responsible for development of NS. Factors associated with NS in people (including "nephrotic-range" serum albumin concentration and urine protein concentration, and particular glomerular disease subtypes) have been assumed previously to also be important in dogs, although descriptions were limited to those patients included in case series of glomerular disease, and sporadic case reports. However, case-control comparison of larger cohorts of dogs with nephrotic versus nonnephrotic glomerular disease more recently suggests that predisposing factors and concurrent clinicopathologic abnormalities differ from those typically encountered in people with nephrotic syndrome, although case progression and negative effect on patient outcome are similar. This article briefly reviews major current theories and supporting evidence on the pathogenesis of NS, followed by an overview on the clinical features of this syndrome in dogs with glomerular disease. The authors also offer evidence-based and experience-based treatment recommendations that are based on minimizing the suspected dysregulation of the renin-angiotensin-aldosterone axis in affected dogs. PMID:21782144

  9. 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

  10. Using evidence-based practice for managing clinical outcomes in advanced practice nursing.

    PubMed

    Glanville, I; Schirm, V; Wineman, N M

    2000-10-01

    Preparation of advanced practice nurses to assume leadership positions for clinical decision making requires that traditional ways of solving clinical problems be augmented with information from relevant, research-derived evidence. In this article, the authors describe how one graduate program prepares advanced practice nurses to use the best scientific evidence with clinical expertise to influence patient outcomes. The assignments that students complete in their program provide examples of evidence-based practice that apply quality improvement principles and science-based nursing interventions to create best practices. PMID:11008434

  11. Central blood pressure: current evidence and clinical importance

    PubMed Central

    McEniery, Carmel M.; Cockcroft, John R.; Roman, Mary J.; Franklin, Stanley S.; Wilkinson, Ian B.

    2014-01-01

    Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an important predictor of future cardiovascular risk. However, systolic pressure varies throughout the arterial tree, such that aortic (central) systolic pressure is actually lower than corresponding brachial values, although this difference is highly variable between individuals. Emerging evidence now suggests that central pressure is better related to future cardiovascular events than is brachial pressure. Moreover, anti-hypertensive drugs can exert differential effects on brachial and central pressure. Therefore, basing treatment decisions on central, rather than brachial pressure, is likely to have important implications for the future diagnosis and management of hypertension. Such a paradigm shift will, however, require further, direct evidence that selectively targeting central pressure, brings added benefit, over and above that already provided by brachial artery pressure. PMID:24459197

  12. Central blood pressure: current evidence and clinical importance.

    PubMed

    McEniery, Carmel M; Cockcroft, John R; Roman, Mary J; Franklin, Stanley S; Wilkinson, Ian B

    2014-07-01

    Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an important predictor of future cardiovascular risk. However, systolic pressure varies throughout the arterial tree, such that aortic (central) systolic pressure is actually lower than corresponding brachial values, although this difference is highly variable between individuals. Emerging evidence now suggests that central pressure is better related to future cardiovascular events than is brachial pressure. Moreover, anti-hypertensive drugs can exert differential effects on brachial and central pressure. Therefore, basing treatment decisions on central, rather than brachial pressure, is likely to have important implications for the future diagnosis and management of hypertension. Such a paradigm shift will, however, require further, direct evidence that selectively targeting central pressure, brings added benefit, over and above that already provided by brachial artery pressure. PMID:24459197

  13. Continuous Glucose Monitoring: Evidence and Consensus Statement for Clinical Use

    PubMed Central

    Liebl, Andreas; Henrichs, Helmut R.; Heinemann, Lutz; Freckmann, Guido; Biermann, Eberhard; Thomas, Andreas

    2013-01-01

    Continuous glucose monitoring (CGM) is an essential tool for modern diabetes therapy. Randomized controlled studies have provided evidence that hemoglobin A1c (HbA1c) results can be improved in patients with type 1 diabetes with elevated baseline HbA1c when using CGM frequently enough and that the frequency and duration of hypoglycemic events can be reduced in patients with satisfactory baseline HbA1c. The CGM group within the Working Group Diabetes Technology (AGDT) of the German Diabetes Association (DDG) has defined evidence-based indications for the practical use of CGM in this consensus statement related to hypoglycemia (frequent, severe, or nocturnal) or hypoglycemia unawareness, insufficient metabolic control despite use of all possible therapeutic options and patient compliance, pregnancy associated with inadequate blood glucose results, and the need for more than 10 blood glucose measurements per day. Contraindications and defined preconditions for the successful use of CGM should be considered. PMID:23567009

  14. Evidence-based treatment for ankle injuries: a clinical perspective

    PubMed Central

    Lin, Chung-Wei Christine; Hiller, Claire E; de Bie, Rob A

    2010-01-01

    The most common ankle injuries are ankle sprain and ankle fracture. This review discusses treatments for ankle sprain (including the management of the acute sprain and chronic instability) and ankle fracture, using evidence from recent systematic reviews and randomized controlled trials. After ankle sprain, there is evidence for the use of functional support and non-steroidal anti-inflammatory drugs. There is weak evidence suggesting that the use of manual therapy may lead to positive short-term effects. Electro-physical agents do not appear to enhance outcomes and are not recommended. Exercise may reduce the occurrence of recurrent ankle sprains and may be effective in managing chronic ankle instability. After surgical fixation for ankle fracture, an early introduction of activity, administered via early weight-bearing or exercise during the immobilization period, may lead to better outcomes. However, the use of a brace or orthosis to enable exercise during the immobilization period may also lead to a higher rate of adverse events, suggesting that this treatment regimen needs to be applied judiciously. After the immobilization period, the focus of treatment for ankle fracture should be on a progressive exercise program. PMID:21655420

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

    PubMed

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

    2015-10-26

    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

  16. 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

  17. Bacterial Lysine Decarboxylase Influences Human Dental Biofilm Lysine Content, Biofilm Accumulation and Sub-Clinical Gingival Inflammation

    PubMed Central

    Lohinai, Z.; Keremi, B.; Szoko, E.; Tabi, T.; Szabo, C.; Tulassay, Z.; Levine, M.

    2012-01-01

    Background Dental biofilms contain a protein that inhibits mammalian cell growth, possibly lysine decarboxylase from Eikenella corrodens. This enzyme decarboxylates lysine, an essential amino acid for dentally attached cell turnover in gingival sulci. Lysine depletion may stop this turnover, impairing the barrier to bacterial compounds. The aims of this study were to determine biofilm lysine and cadaverine contents before oral hygiene restriction (OHR), and their association with plaque index (PI) and gingival crevicular fluid (GCF) after OHR for a week. Methods Laser-induced fluorescence after capillary electrophoresis was used to determine lysine and cadaverine contents in dental biofilm, tongue biofilm and saliva before OHR and in dental biofilm after OHR. Results Before OHR, lysine and cadaverine contents of dental biofilm were similar and 10-fold greater than in saliva or tongue biofilm. After a week of OHR, the biofilm content of cadaverine increased and that of lysine decreased, consistent with greater biofilm lysine decarboxylase activity. Regression indicated that PI and GCF exudation were positively related to biofilm lysine post-OHR, unless biofilm lysine exceeded the minimal blood plasma content in which case PI was further increased but GCF exudation was reduced. Conclusions After OHR, lysine decarboxylase activity seems to determine biofilm lysine content and biofilm accumulation. When biofilm lysine exceeds minimal blood plasma content after OHR, less GCF appeared despite more biofilm. Lysine appears important for biofilm accumulation and the epithelial barrier to bacterial proinflammatory agents. Clinical Relevance Inhibiting lysine decarboxylase may retard the increased GCF exudation required for microbial development and gingivitis. PMID:22141361

  18. 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

  19. 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

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

    PubMed

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

    2016-01-01

    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

  1. Clinical and laboratory evidence for Neisseria meningitidis biofilms

    PubMed Central

    Neil, R Brock; Apicella, Michael A

    2010-01-01

    Neisseria meningitidis is the etiologic agent of meningococcal meningitis. Carriage of the organism is approximately 10% while active disease occurs at a rate of 1:100,000. Recent publications demonstrate that N. meningitidis has the ability to form biofilms on glass, plastic or cultured human bronchial epithelial cells. Microcolony-like structures are also observed in histological sections from patients with active meningococcal disease. This review investigates the possible role of meningococcal biofilms in carriage and active disease, based on the laboratory and clinical aspects of the disease. PMID:19492966

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

    PubMed Central

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

    2008-01-01

    Summary Evidence-based medicine (EBM) is the clinical use of current best available evidence from relevant, valid research. Provision of evidence-based healthcare is the most ethical way to practise as it integrates up-to-date patient-oriented research into the clinical decision-making to improve patients' outcomes. This article provides tips for teachers to teach clinical trainees the final two steps of EBM: integrating evidence with clinical judgement and bringing about change. PMID:19029354

  3. 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

  4. Clinical evidence of interaction between clopidogrel and proton pump inhibitors

    PubMed Central

    Lin, Shoa-Lin; Chang, Hui-Min; Liu, Chun-Peng; Chou, Li-Ping; Chan, Jaw-Wen

    2011-01-01

    Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular (CV) and cerebrovascular disease. Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention, compared with aspirin alone. Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy, current guidelines recommend combined use of a proton pump inhibitor (PPI) to decrease the risk of bleeding. Data from previous pharmacological studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients receiving both clopidogrel and PPIs than in those without PPIs. However, other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users. These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs, existing clinical data regarding the interaction between clopidogrel and PPIs, and tries to provide recommendations for health care professionals. PMID:21666816

  5. Transcutaneous Electrical Nerve Stimulation: Mechanisms, Clinical Application and Evidence

    PubMed Central

    2007-01-01

    Transcutaneous electrical nerve stimulation (TENS) is a non-invasive, inexpensive, self-administered technique to relieve pain.There are few side effects and no potential for overdose so patients can titrate the treatment as required.TENS techniques include conventional TENS, acupuncture-like TENS and intense TENS. In general, conventional TENS is used in the first instance.The purpose of conventional TENS is to selectively activate large diameter non-noxious afferents (A-beta) to reduce nociceptor cell activity and sensitization at a segmental level in the central nervous system.Pain relief with conventional TENS is rapid in onset and offset and is maximal when the patient experiences a strong but non-painful paraesthesia beneath the electrodes. Therefore, patients may need to administer TENS throughout the day.Clinical experience suggests that TENS may be beneficial as an adjunct to pharmacotherapy for acute pain although systematic reviews are conflicting. Clinical experience and systematic reviews suggest that TENS is beneficial for chronic pain. PMID:26526976

  6. Human pharmacology for addiction medicine: From evidence to clinical recommendations.

    PubMed

    Quednow, Boris B; Herdener, Marcus

    2016-01-01

    Substance use disorders (SUD) are complex and often chronic diseases with negative health outcomes and social consequences. Pharmacological treatment options for SUD can be separated in medications for (i) intoxication, (ii) withdrawal, and (iii) reduction of use together with relapse prevention. This chapter will focus on approved or clinically established pharmacological strategies suited to manage symptoms of withdrawal, and to reduce substance use or to promote abstinence. Hereby SUD involving alcohol, nicotine, stimulants, and opioids are primarily discussed as these substances are considered most harmful for both the individual and the society. Moreover, the pharmacotherapy of SUD related to the use of cannabis, benzodiazepines, and gamma-hydroxybutyrate is also briefly reviewed. Since most approved pharmacological treatment options show only moderate effect sizes especially in the long term, the development of new treatment strategies including new drugs, new combinations of available compounds, and biomarkers for response prediction is still warranted. PMID:26822361

  7. Dabigatran in clinical practice: Contemporary overview of the evidence.

    PubMed

    Ageno, Walter; Eikelboom, John; Lip, Gregory Y H

    2016-10-01

    Oral anticoagulation is the cornerstone of stroke prevention in non-valvular atrial fibrillation (AF) and management of venous thromboembolism (VTE), resulting in a reduction in thrombotic complications and mortality. Benefit of vitamin K antagonists (VKAs) in such patients has been unambiguously confirmed, but VKA use is complicated by need for regular monitoring of the international normalized ratio and multiple drug and food interactions. Dabigatran is an oral direct thrombin inhibitor that can be used with fixed doses, without the need for routine anticoagulation laboratory monitoring and the advantage of few drug or diet interactions. Dabigatran is effective for stroke and systemic thromboembolism in AF and for the prophylaxis and treatment of VTE. The drug has a good safety profile and consistently shows a reduction in intracranial hemorrhage risk compared to warfarin. A specific reversal agent for dabigatran has been approved by FDA and EU. This review provides a summary of publications assessing clinical utility of dabigatran for different indications. PMID:27390965

  8. 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

  9. Atherosclerosis in psoriatic disease: latest evidence and clinical implications

    PubMed Central

    Eder, Lihi; Gladman, Dafna D.

    2015-01-01

    It is widely accepted that atherosclerosis is caused by chronic low-grade inflammation that results from an interaction between immune mechanisms and metabolic abnormalities within the vessel wall. Population-based studies have found an increased cardiovascular risk in patients with psoriasis and psoriatic arthritis (PsA). This risk is higher in patients with severe disease phenotypes, such as those with severe psoriasis and with musculoskeletal inflammation. Higher levels of inflammatory biomarkers also predict the development of clinical cardiovascular events in these patients. The effect of medications used for PsA on cardiovascular risk is limited to observational studies. Antitumor necrosis factor agents and methotrexate have been associated with reduced cardiovascular risk. These data highlight the importance of screening for cardiovascular risk factors in these patients. PMID:26425147

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

    PubMed

    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

  11. Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information – ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) – study protocol

    PubMed Central

    Moja, Lorenzo; Moschetti, Ivan; Cinquini, Michela; Sala, Valeria; Compagnoni, Anna; Duca, Piergiorgio; Deligant, Christian; Manfrini, Roberto; Clivio, Luca; Satolli, Roberto; Addis, Antonio; Grimshaw, Jeremy M; Dri, Pietro; Liberati, Alessandro

    2008-01-01

    Background In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence. Design All Italian doctors naïve to ECCE will be randomised to three groups. Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of Clinical Evidence. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics. Trial registration ISRCTN27453314 PMID:18637189

  12. 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

  13. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

    PubMed Central

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-01-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness. PMID:26862501

  14. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence.

    PubMed

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-02-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness. PMID:26862501

  15. Evidence-based early clinical detection of emerging diseases in food animals and zoonoses: two cases.

    PubMed

    Saegerman, Claude; Humblet, Marie-France; Porter, Sarah Rebecca; Zanella, Gina; Martinelle, Ludovic

    2012-03-01

    If diseases of food-producing animals or zoonoses (re-)emerge, early clinical decision making is of major importance. In this particular condition, it is difficult to apply a classic evidence-based veterinary medicine process, because of a lack of available published data. A method based on the partition of field clinical observations (evidences) could be developed as an interesting alternative approach. The classification and regression tree (CART) analysis was used to improve the early clinical detection in two cases of emerging diseases: bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the serotype 8-virus in cattle. PMID:22374122

  16. 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. PMID:27583147

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

    PubMed Central

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

    2016-01-01

    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. PMID:27583147

  18. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26929788

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

    PubMed Central

    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. PMID:26770666

  1. Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance

    PubMed Central

    2014-01-01

    The incidence of Clostridium difficile infection (CDI) has risen 400% in the last decade. It currently ranks as the third most common nosocomial infection. CDI has now crossed over as a community-acquired infection. The major failing of current therapeutic options for the management of CDI is recurrence of disease after the completion of treatment. Fidaxomicin has been proven to be superior to vancomycin in successful sustained clinical response to therapy. Improved outcomes may be due to reduced collateral damage to the gut microflora by fidaxomicin, bactericidal activity, inhibition of Clostridial toxin formation and inhibition of new sporulation. This superiority is maintained in groups previously reported as being at high risk for CDI recurrence including those: with relapsed infection after a single treatment course; on concomitant antibiotic therapy; aged >65 years; with cancer; and with chronic renal insufficiency. Because the acquisition cost of fidaxomicin far exceeds that of metronidazole or vancomycin, in order to rationally utilize this agent, it should be targeted to those populations who are at high risk for relapse and in whom the drug has demonstrated superiority. In this manuscript is reviewed the changing epidemiology of CDI, current treatment options for this infection, proposed benefits of fidaxomicin over currently available antimicrobial options, available analysis of cost effectiveness of the drug, and is given recommendations for judicious use of the drug based upon the available published literature. PMID:24587892

  2. 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. PMID:26770666

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

    PubMed

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

    2010-07-01

    This study examines the effects of integrating evidence-based practice (EBP) into clinical practicum on EBP efficacy and barriers to research utilization among Korean RN-to-BSN students. A one-group pretest-posttest design was used. Eighty-one students were recruited from a school of nursing in Korea. Evidence-based practice clinical practicum was composed of two consecutive programs during one semester. Lectures, individual mentoring on EBP practicum, small group, and wrap-up conferences were provided. Outcomes of EBP efficacy and barriers to research utilization were analyzed using paired t tests for 74 final participants. Evidence-based practice efficacy scores increased significantly (p < 0.05), and the barriers to research utilization scores decreased significantly after the EBP clinical practicum. The results highlight the effectiveness of EBP education among RN-to-BSN students. These results may help health educators develop effective educational strategies to integrate EBP concepts into a clinical practicum. PMID:20411864

  4. 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.

  5. Evidence-based clinical use of insulin premixtures.

    PubMed

    Tambascia, Marcos Antônio; Nery, Márcia; Gross, Jorge Luiz; Ermetice, Mariana Narbot; de Oliveira, Carolina Piras

    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

  6. 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

  7. Neurodegeneration with Brain Iron Accumulation

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Neurodegeneration with Brain Iron Accumulation Information Page Synonym(s): Hallervorden-Spatz Disease, ... done? Clinical Trials Organizations What is Neurodegeneration with Brain Iron Accumulation? Neurodegeneration with brain iron accumulation (NBIA) ...

  8. 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

  9. 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

  10. Towards an evidence-based process for the clinical interpretation of copy number variation

    PubMed Central

    Riggs, ER; Church, DM; Hanson, K; Horner, VL; Kaminsky, EB; Kuhn, RM; Wain, KE; Williams, ES; Aradhya, S; Kearney, HM; Ledbetter, DH; South, ST; Thorland, EC; Martin, CL

    2016-01-01

    The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design. PMID:22097934

  11. 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. PMID:26195697

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. Integrating Evidence-Based Tobacco Cessation Interventions in Free Medical Clinics: Opportunities and Challenges

    PubMed Central

    Foley, Kristie L.; Pockey, Jessica R.; Helme, Donald W.; Song, Eun-Young; Stewart, Kate; Jones, Cindy; Spangler, John G.; Sutfin, Erin L.

    2013-01-01

    Background Free medical clinics serve a critical role in health care delivery of America’s uninsured population, who are less likely to receive tobacco cessation counseling and 1½ times more likely than the general population to use tobacco. The authors evaluate the opportunities for and challenges to implementing the U.S. Public Health Service Guidelines for tobacco cessation in free clinics. Methods Six free clinics participated in this pilot study. Five objectives were targeted: implementation of a tobacco user identification system, education of all clinic staff and volunteers, dedication of a program champion, use of evidence-based treatment, and creation of a supportive environment that reinforces provider behavior. Key informant interviews and focus group data were used to describe the opportunities and barriers of implementing the Public Health Service Guidelines. Results All clinics adopted a user identification system, dedicated a program champion, adopted evidence-based counseling, and created an environment conducive for cessation. Common challenges included getting volunteers to attend on-site training programs, accessing nicotine replacement therapy, and promoting Quit Line usage, all of which are part of evidence-based treatment. Conclusion With more than 1,200 free clinics nationwide, it is very important to understand the opportunities and barriers of implementing tobacco cessation services and systems in free clinics. PMID:22467664

  15. Methods underpinning national clinical guidelines for hypertension: describing the evidence shortfall

    PubMed Central

    Campbell, Fiona; Dickinson, Heather O; Cook, Julia VF; Beyer, Fiona R; Eccles, Martin; Mason, James M

    2006-01-01

    Background To be useful, clinical practice guidelines need to be evidence based; otherwise they will not achieve the validity, reliability and credibility required for implementation. Methods This paper compares the methods used in gathering, analysing and linking of evidence to guideline recommendations in ten current hypertension guidelines. Results It found several guidelines had failed to implement methods of searching for the relevant literature, critical analysis and linking to recommendations that minimise the risk of bias in the interpretation of research evidence. The more rigorous guidelines showed discrepancies in recommendations and grading that reflected different approaches to the use of evidence in guideline development. Conclusion Clinical practice guidelines as a methodology are clearly still an evolving health care technology. PMID:16597334

  16. Review: Evidence-based Clinical Research of Anti-obesity Supplements in Japan

    PubMed Central

    Yasueda, Asuka; Ito, Toshinori; Maeda, Kazuhisa

    2013-01-01

    Background: The prevalence of obesity has increased dramatically throughout the world, and weight reduction through lifestyle management is urgently warranted. At present, numerous supplements advertised for their anti-overweight property are available in the Japanese market, but most of these lack proper evidence. Thus, we investigated dietary supplements that have been tested in clinical trials. Search Strategy: We researched anti-obesity supplements in the Japanese market using the google search engine in Japanese with the key terms “anti-obesity supplements,” ”diet supplements,” and “weight reduction supplements.” Results: We listed 49 companies that supply anti-obesity supplements. Of these, 11 had published clinical evidence of the anti-obesity efficacy of their supplements. These products contain the following active ingredients: Angelica keiskei, bofu-tsusho-san, capsaishin, DHA/EPA, forskohlii, garcinia cambogia, lactoferrin, L-carnitine, oligonol, tea catechin, and yeast hydrolysate. Conclusion: We obtained 11 supplements for which clinical evidence was published in medical journals in English. We also found 10 products for which clinical or animal evidence was published in Japanese. We expect that many companies will produce evidence of the efficacy of their products in the near future, thereby validating the use of dietary anti-obesity supplements in Japan. PMID:26005506

  17. [Evidence and recommendations for oncologic clinical exercise - a personalized treatment concept for cancer patients].

    PubMed

    Baumann, Freerk Theeagnus; Hallek, Michael; Meyer, Janika; Galvão, Daniel Abido; Bloch, Wilhelm; Elter, Thomas

    2015-09-01

    Oncological treatments can lead to acute and chronic cancer related toxicities. In recent years, a large number of clinical studies have reported positive effects of exercise to the bio-psycho-social regeneration of cancer patients. However, very few evidence-based programs have been implemented into practice with little opportunity for cancer patients to engage in such programs. Reviews and RCT studies on exercise and cancer are showing that specific exercise programs have a positive impact on fatigue syndrome, urinary incontinence, lymphedema, polyneuropathy, arthralgia, and androgen deprivation related toxicities. With the increasing evidence for exercise oncology interventions, recommendations arising from clinical trials should be translated into clinical practice and this should be viewed as an important next step in this fast moving field of exercise oncology. For that the personalized treatment concept "Oncologic clinical exercise" (OTT) was developed. PMID:26402184

  18. 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

  19. 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

  20. Accumulation of fructose 1,6-bisphosphate in mutant cells of mucoid Pseudomonas aeruginosa as an evidence of phosphofructokinase activity.

    PubMed

    Banerjee, P C

    1986-05-01

    Phosphoglucose isomerase negative mutant of mucoid Pseudomonas aeruginosa accumulated relatively higher concentration of fructose 1,6-bisphosphate (Fru-1,6-P2) when mannitol induced cells were incubated with this sugar alcohol. Also the toluene-treated cells of fructose 1,6-bisphosphate aldolase negative mutant of this organism produced Fru-1,6-P2 from fructose 6-phosphate in presence of ATP, but not from 6-phosphogluconate. The results together suggested the presence of an ATP-dependent fructose 6-phosphate kinase (EC 2.7.1.11) in mucoid P. aeruginosa. PMID:3017251

  1. 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. PMID:12512984

  2. Better Management of Cardiovascular Diseases by Pulse Wave Velocity: Combining Clinical Practice with Clinical Research using Evidence-Based Medicine

    PubMed Central

    Khoshdel, Ali R.; Carney, Shane L.; Nair, Balakrishnan R.; Gillies, Alastair

    2007-01-01

    Arterial stiffness measured by pulse wave velocity (PWV) is an accepted strong, independent predictor of cardiovascular events and mortality. However, lack of a reliable reference range has limited its use in clinical practice. In this evidence-based review, we applied published data to develop a PWV risk stratification model and demonstrated its impact on the management of common clinical scenarios. After reviewing 97 studies where PWV was measured, 5 end-stage renal disease patients, 5 hypertensives, 2 diabetics, and 2 elderly studies were selected. Pooling the data by the “fixed-effect model” demonstrated that the mortality and cardiovascular event risk ratio for one level increment in PWV was 2.41 (1.81–3.20) or 1.69 (1.35–2.11), respectively. There was a significant difference in PWV between survived and deceased groups, both in the low and high risk populations. Furthermore, risk comparison demonstrated that 1 standard deviation increment in PWV is equivalent to 10 years of aging, or 1.5 to 2 times the risk of a 10 mmHg increase in systolic blood pressure. Evidence shows that PWV can be beneficially used in clinical practice for cardiovascular risk stratification. Furthermore, the above risk estimates could be incorporated into currently used cardiac risk scores to improve their predictive power and facilitate the clinical application of PWV. PMID:17456834

  3. 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. PMID:23463942

  4. Dietary Nitrate Lowers Blood Pressure: Epidemiological, Pre-clinical Experimental and Clinical Trial Evidence.

    PubMed

    Gee, Lorna C; Ahluwalia, Amrita

    2016-02-01

    Nitric oxide (NO), a potent vasodilator critical in maintaining vascular homeostasis, can reduce blood pressure in vivo. Loss of constitutive NO generation, for example as a result of endothelial dysfunction, occurs in many pathological conditions, including hypertension, and contributes to disease pathology. Attempts to therapeutically deliver NO via organic nitrates (e.g. glyceryl trinitrate, GTN) to reduce blood pressure in hypertensives have been largely unsuccessful. However, in recent years inorganic (or 'dietary') nitrate has been identified as a potential solution for NO delivery through its sequential chemical reduction via the enterosalivary circuit. With dietary nitrate found in abundance in vegetables this review discusses epidemiological, pre-clinical and clinical data supporting the idea that dietary nitrate could represent a cheap and effective dietary intervention capable of reducing blood pressure and thereby improving cardiovascular health. PMID:26815004

  5. Clinical Utility of Combinatorial Pharmacogenomics-Guided Antidepressant Therapy: Evidence from Three Clinical Studies.

    PubMed

    Altar, C Anthony; Carhart, Joseph; Allen, Josiah D; Hall-Flavin, Daniel; Winner, Joel; Dechairo, Bryan

    2015-10-01

    DNA of 258 patients with treatment-resistant depression was collected in three 8-10 week, two-arm, prospective clinical trials. Forty-four allelic variations were measured in genes for the cytochrome P450 (CYP) enzymes CYP2D6, CYPC19, and CYP1A2, the serotonin transporter (SLC6A4), and the 5-HT2A receptor (HTR2A). The combinatorial pharmacogenomic (CPGx™) GeneSight test results were provided to clinicians to support medication changes from baseline (guided arm), or they were provided at the end of each study to clinicians of unguided patients who were treated as usual (TAU). TAU subjects who at baseline were prescribed medications genetically discordant for them showed only a 12% symptom improvement, far less than the 32.5% or 28.5% improvements of the TAU subjects on yellow-category ('use with caution'; p = 0.002) or green-category medications ('use as recommended'; p = 0.02), respectively. The odds of a clinical response were increased 2.3-fold among all GeneSight-guided compared to all TAU subjects (p = 0.004), and overall, the guided group had a 53% greater improvement in depressive symptoms (p = 0.0002), a 1.7-fold relative improvement in response (p = 0.01), and a number needed to treat for one clinical response above that seen in the TAU group of 6.07. PMID:27606312

  6. 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

  7. First evidence for accumulation of protein-bound and protein-free pyrraline in human uremic plasma by mass spectrometry.

    PubMed

    Odani, H; Shinzato, T; Matsumoto, Y; Takai, I; Nakai, S; Miwa, M; Iwayama, N; Amano, I; Maeda, K

    1996-07-01

    Glucose-derived advanced glycation end products (AGEs) cross-link proteins and cause various biological tissue damage. One of them, pyrraline [epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl) -L-norleucine], has been demonstrated by utilizing antibody to accumulate in plasma and sclerosed matrix of diabetic individuals, suggesting responsibility for diabetic complications. To elucidate the involvement of pyrraline in uremia, we examined the pyrraline levels in patients with chronic renal failure by a mass spectrometric approach. Here we show that protein-free pyrraline as well as pyrraline with binding protein are significantly increased in non-diabetic uremic plasma compared to healthy subjects. Our results suggest that circulating pyrraline could be a substance contributing to complications in uremia. PMID:8694819

  8. 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

  9. Towards combinatorial targeted therapy in melanoma: From pre-clinical evidence to clinical application (Review)

    PubMed Central

    GRAZIA, GIULIA; PENNA, ILARIA; PEROTTI, VALENTINA; ANICHINI, ANDREA; TASSI, ELENA

    2014-01-01

    Over the last few years, clinical trials with BRAF and mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors have shown significant clinical activity in melanoma, but only a fraction of patients respond to these therapies, and development of resistance is frequent. This has prompted a large set of preclinical studies looking at several new combinatorial approaches of pathway- or target-specific inhibitors. At least five main drug association strategies have been verified in vitro and in preclinical models. The most promising include: i) vertical targeting of either MEK or phosphoinositide-3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways, or their combined blockade; ii) association of receptor tyrosine kinases (RTKs) inhibitors with other pro-apoptotic strategies; iii) engagement of death receptors in combination with MEK-, mTOR/PI3K-, histone deacetylase (HDAC)-inhibitors, or with anti-apoptotic molecules modulators; iv) strategies aimed at blocking anti-apoptotic proteins belonging to B-cell lymphoma (Bcl-2) or inhibitors of apoptosis (IAP) families associated with MEK/BRAF/p38 inhibition; v) co-inhibition of other molecules important for survival [proteasome, HDAC and Signal transducers and activators of transcription (Stat)3] and the major pathways activated in melanoma; vi) simultaneous targeting of multiple anti-apoptotic molecules. Here we review the anti-melanoma efficacy and mechanism of action of the above-mentioned combinatorial strategies, together with the potential clinical application of the most promising studies that may eventually lead to therapeutic benefit. PMID:24920406

  10. 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).…

  11. 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…

  12. A Web-Based Compendium of Clinical Questions and Medical Evidence To Educate Internal Medicine Residents.

    ERIC Educational Resources Information Center

    Crowley, Steven H.; Owens, Thomas A.; Schardt, Connie M.; Wardell, Sarah I.; Peterson, Josh; Garrison, Scott; Keitz, Sheri A.

    2003-01-01

    Describes an electronic database of clinical questions (CQs) and medical evidence, the Critical Appraisal Resource (CAR). Evaluation of ten months of use found that medical residents did engage the medical literature on behalf of their patients, which influenced approximately half of their patient-care decisions. (EV)

  13. 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…

  14. The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications.

    PubMed

    Stugiewicz, Magdalena; Tkaczyszyn, Michał; Kasztura, Monika; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

    2016-07-01

    Skeletal and respiratory myopathy not only constitutes an important pathophysiological feature of heart failure and chronic obstructive pulmonary disease, but also contributes to debilitating symptomatology and predicts worse outcomes in these patients. Accumulated evidence from laboratory experiments, animal models, and interventional studies in sports medicine suggests that undisturbed systemic iron homeostasis significantly contributes to the effective functioning of skeletal muscles. In this review, we discuss the role of iron status for the functioning of skeletal muscle tissue, and highlight iron deficiency as an emerging therapeutic target in chronic diseases accompanied by a marked muscle dysfunction. PMID:26800032

  15. Legislating Clinical Practice: Counselor Responses to an Evidence-Based Practice Mandate

    PubMed Central

    Rieckmann, Traci; Bergmann, Luke; Rasplica, Caitlin

    2013-01-01

    The demand to connect research findings with clinical practice for patients with substance use disorders has accelerated state and federal efforts focused on implementation of evidence-based practices (EBPs). One unique state driven strategy is Oregon’s Evidence-Based Practice mandate, which ties state funds to specific treatment practices. Clinicians play an essential role in implementation of shifts in practice patterns and use of EBPs, but little is understood about how legislative efforts impact clinicians’ sentiments and decision-making. This study presents longitudinal data from focus groups and interviews completed during the planning phase (n = 66) and early implementation of the mandate (n = 73) to investigate provider attitudes toward this policy change. Results reflect three emergent themes: (1) concern about retaining individualized treatment and clinical latitude, (2) distrust of government involvement in clinical care, and (3) the need for accountability and credibility for the field. We conclude with recommendations for state agencies considering EBP mandates. PMID:22185037

  16. Framework and guidance for implementing patient-reported outcomes in clinical practice: evidence, challenges and opportunities.

    PubMed

    Porter, Ian; Gonçalves-Bradley, Daniela; Ricci-Cabello, Ignacio; Gibbons, Chris; Gangannagaripalli, Jaheeda; Fitzpatrick, Ray; Black, Nick; Greenhalgh, Joanne; Valderas, Jose M

    2016-08-01

    Patient-reported outcomes (PROs) are reports of the status of a patient's health condition that come directly from the patient. While PRO measures are a well-developed technology with robust standards in research, their use for informing healthcare decisions is still poorly understood. We review relevant examples of their application in the provision of healthcare and examine the challenges associated with implementing PROs in clinical settings. We evaluate evidence for their use and examine barriers to their uptake, and present an evidence-based framework for the successful implementation of PROs in clinical practice. We discuss current and future developments for the use of PROs in clinical practice, such as individualized measurement and computer-adaptive testing. PMID:27427277

  17. Legislating clinical practice: counselor responses to an evidence-based practice mandate.

    PubMed

    Rieckmann, Traci; Bergmann, Luke; Rasplica, Caitlin

    2011-09-01

    The demand to connect research findings with clinical practice for patients with substance use disorders has accelerated state and federal efforts focused on implementation of evidence-based practices (EBPs). One unique state driven strategy is Oregon's Evidence-Based Practice mandate, which ties state funds to specific treatment practices. Clinicians play an essential role in implementation of shifts in practice patterns and use of EBPs, but little is understood about how legislative efforts impact clinicians' sentiments and decision-making. This study presents longitudinal data from focus groups and interviews completed during the planning phase (n = 66) and early implementation of the mandate (n = 73) to investigate provider attitudes toward this policy change. Results reflect three emergent themes: (1) concern about retaining individualized treatment and clinical latitude, (2) distrust of government involvement in clinical care, and (3) the need for accountability and credibility for the field. We conclude with recommendations for state agencies considering EBP mandates. PMID:22185037

  18. The legitimacy of placebo treatments in clinical practice: evidence and ethics.

    PubMed

    Miller, Franklin G; Colloca, Luana

    2009-12-01

    Physicians commonly recommend 'placebo treatments', which are not believed to have specific efficacy for the patient's condition. Motivations for placebo treatments include complying with patient expectations and promoting a placebo effect. In this article, we focus on two key empirical questions that must be addressed in order to assess the ethical legitimacy of placebo treatments in clinical practice: 1) do placebo treatments have the potential to produce clinically significant benefit? and 2) can placebo treatments be effective in promoting a therapeutic placebo response without the use of deception? We examine evidence from clinical trials and laboratory experiments bearing on these two questions. The conclusion is reached that based on currently available evidence, it is premature to judge whether placebo treatments are ethically justifiable, with the possible exception of acupuncture for pain relief. PMID:20013499

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  20. Primary care evidence in clinical guidelines: a mixed methods study of practitioners’ views

    PubMed Central

    Abdelhamid, Asmaa; Howe, Amanda; Stokes, Tim; Qureshi, Nadeem; Steel, Nick

    2014-01-01

    Background Clinical practice guidelines are widely used in primary care, yet are not always based on applicable research. Aim To explore primary care practitioners’ views on the applicability to primary care patients of evidence underpinning National Institute for Health and Care Excellence (NICE) guideline recommendations. Design and setting Delphi survey and focus groups in primary care, England, UK. Method Delphi survey of the perceived applicability of 14 guideline recommendations rated before and after a description of their evidence base, followed by two focus groups. Results GPs significantly reduced scores for their perceived likelihood of pursuing recommendations after finding these were based on studies with low applicability to primary care, but maintained their scores for recommendations based on highly applicable research. GPs reported they were more likely to use guidelines where evidence was applicable to primary care, and less likely if the evidence base came from a secondary care population. Practitioners in the focus groups accepted that guideline developers would use the most relevant evidence available, but wanted clearer signposting of those recommendations particularly relevant for primary care patients. Their main need was for brief, clear, and accessible guidelines. Conclusion Guidelines should specify the extent to which the research evidence underpinning each recommendation is applicable to primary care. The relevance of guideline recommendations to primary care populations could be more explicitly considered at all three stages of guideline development: scoping and evidence synthesis, recommendation development, and publication. The relevant evidence base needs to be presented clearly and concisely, and in an easy to identify way. PMID:25348996

  1. "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. PMID:25743760

  2. 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

  3. 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.

  4. Temporal trends of triclosan contamination in dated sediment cores from four urbanized estuaries: evidence of preservation and accumulation.

    PubMed

    Cantwell, Mark G; Wilson, Brittan A; Zhu, Jun; Wallace, Gordon T; King, John W; Olsen, Curtis R; Burgess, Robert M; Smith, Joseph P

    2010-01-01

    Triclosan is an antimicrobial agent added to a wide array of consumer goods and personal care products. Through its use, it is introduced into municipal sewer systems where it is only partially removed during wastewater treatment. In this study, triclosan was measured in dated sediment cores from four urbanized estuaries in order to reconstruct temporal and spatial trends of accumulation. Measurable concentrations of triclosan first appeared in each of the sediment cores near 1964, which corresponds with the US patent issuance date of triclosan. The presence of triclosan at each of the study sites at or near the patent date indicates that long-term preservation is occurring in estuarine sediments. Temporal trends of triclosan at each location are unique, reflecting between site variability. Concentrations at one site climbed to as high as 400ngg(-1), due in part, to local commercial production of triclosan. At two locations, levels of triclosan rise towards the surface of each core, suggesting increasing usage in recent years. One location adjacent to a major combined sewer overflow had high sediment concentrations of triclosan, confirming their potential as a source of triclosan to estuaries. PMID:20006371

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

    PubMed Central

    Doyle, Cathal; Lennox, Laura; Bell, Derek

    2013-01-01

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

  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. PMID:21927777

  7. Rapid and frequent turbidite accumulation in the bottom of Izu-Ogasawara Trench: Chemical and radiochemical evidence

    NASA Astrophysics Data System (ADS)

    Nozaki, Yoshiyuki; Ohta, Yoichi

    1993-12-01

    Two sediment cores (pilot gravity and piston) were obtained from the bottom of the Izu-Ogasawara Trench at 9750 m and analyzed for various elements and radioisotopes. The results showed a history of complex and frequent turbidite deposition: In the gravity core, eight layers rich in manganese were observed, of which five are enriched in Cu and Co as well. The other three are also enriched in Mo but no other heavy metals, suggesting the presence of at least two mechanisms of formation. Trapping of iron manganese micronodules can account for the enrichment of Mn, Cu and Co. The other three layers rich in Mn and Mo appear to be formed by a post-depositional diagenetic process of Mn mobilization and redeposition in the sediment column. A strong correlation between Ra-226 and Cu in the gravity core suggests that the Ra-226 was also carried into the bottom of the trench in turbidites in association with Mn micronodules. Little excess of Pb-210 over Ra-226 was found at the top but the excess was significant at mid-depths from 30 to 70 cm, indicating that those sediments were deposited within the last 200 y. In the piston core there is a sharp discontinuity of chemical and radiochemical composition around a depth of 250 cm. Below that depth the sediments appear to be dominated by materials derived from terrestrial sources, as compared with those in the upper layer which are of contemporary marine origin. Ra-226 is deficient relative to Th-230 throughout the sediment column down to about 6 m. This finding is consistent with the finding that the average rate of sediment accumulation is 1-2 orders of magnitude faster than that in the western North Pacific abyssal plain, suggesting the convergence of materials into the bottom of the trench.

  8. Is ophthalmology evidence based? A clinical audit of the emergency unit of a regional eye hospital

    PubMed Central

    Lai, T Y Y; Wong, V W Y; Leung, G M

    2003-01-01

    Aim: To evaluate the proportion of interventions that are evidence based in the acute care unit of a regional eye hospital. Methods: A prospective clinical audit was carried out at Hong Kong Eye Hospital in July 2002 to investigate the extent to which ophthalmic practices were evidence based. The major diagnosis and intervention provided were identified through chart review. A corresponding literature search using Medline and the Cochrane Library was performed to assess the degree to which each intervention was based on current, best evidence. Each diagnosis intervention pair was accordingly analysed and graded. The level of best, current evidence supporting each intervention was graded and analysed. Results: A total of 274 consecutive consultation episodes were examined. 22 cases were excluded since no diagnosis or intervention was made during the consultation. 108 (42.9%) patient interventions were found to be based on evidence from systematic reviews, meta-analyses, or randomised controlled trials (RCT). Evidence from prospective or retrospective observational studies supported the interventions in 86 (34.1%) patients. In 58 (23.0%) cases, no evidence or opposing evidence was found regarding the intervention. The proportion of evidence based on RCT or systematic reviews was higher for surgical interventions compared with non-surgical interventions (p=0.007). The proportion of interventions based on RCT or systematic reviews was higher for specialist ophthalmologists than trainee ophthalmologists (p=0.021). Conclusion: This study demonstrated that the majority of interventions in the ophthalmic unit were evidence based and comparable to the experience of other specialties. PMID:12642295

  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

    2016-01-01

    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

  10. In vivo (/sup 3/H)spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    SciTech Connect

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-06-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist (3H)spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo (3H)spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of (3H)spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound (3H)spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to (3H)spiperone injection resulted in a selective increase of in vivo (3H)spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.

  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. Use of Incisional Negative Pressure Wound Therapy on Closed Median Sternal Incisions after Cardiothoracic Surgery: Clinical Evidence and Consensus Recommendations

    PubMed Central

    Dohmen, Pascal M.; Markou, Thanasie; Ingemansson, Richard; Rotering, Heinrich; Hartman, Jean M.; van Valen, Richard; Brunott, Maaike; Segers, Patrique

    2014-01-01

    Negative pressure wound therapy is a concept introduced initially to assist in the treatment of chronic open wounds. Recently, there has been growing interest in using the technique on closed incisions after surgery to prevent potentially severe surgical site infections and other wound complications in high-risk patients. Negative pressure wound therapy uses a negative pressure unit and specific dressings that help to hold the incision edges together, redistribute lateral tension, reduce edema, stimulate perfusion, and protect the surgical site from external infectious sources. Randomized, controlled studies of negative pressure wound therapy for closed incisions in orthopedic settings (which also is a clean surgical procedure in absence of an open fracture) have shown the technology can reduce the risk of wound infection, wound dehiscence, and seroma, and there is accumulating evidence that it also improves wound outcomes after cardiothoracic surgery. Identifying at-risk individuals for whom prophylactic use of negative pressure wound therapy would be most cost-effective remains a challenge; however, several risk-stratification systems have been proposed and should be evaluated more fully. The recent availability of a single-use, closed incision management system offers surgeons a convenient and practical means of delivering negative pressure wound therapy to their high-risk patients, with excellent wound outcomes reported to date. Although larger, randomized, controlled studies will help to clarify the precise role and benefits of such a system in cardiothoracic surgery, limited initial evidence from clinical studies and from the authors’ own experiences appears promising. In light of the growing interest in this technology among cardiothoracic surgeons, a consensus meeting, which was attended by a group of international experts, was held to review existing evidence for negative pressure wound therapy in the prevention of wound complications after surgery and

  13. Using Mobile Technologies to Access Evidence-Based Resources: A Rural Health Clinic Experience.

    PubMed

    Carter-Templeton, Heather D; Wu, Lin

    2015-09-01

    This study describes the feasibility and usability of a mobile device and selected electronic evidence-based information programs used to support clinical decision making in a rural health clinic. The study focused on nurses' perceptions on when they needed more information, where they sought information, what made them feel comfortable about the information they found, and rules and guidelines they used to determine if the information should be used in patient care. ATLAS.ti, the qualitative analysis software, was used to assist with qualitative data analysis and management. PMID:26333613

  14. 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

  15. Using focused reflection and articulation to promote clinical reasoning: an evidence-based teaching strategy.

    PubMed

    Murphy, Judy Irene

    2004-01-01

    This research explored the effects of instructing first-semester nursing students in the use of focused reflection and articulation to promote clinical reasoning. Student volunteers were randomly assigned to four clinical groups. Two groups that received instruction in the use of focused reflection and articulation scored significantly higher on the practice measure of clinical reasoning, accounting for 29 percent of the variance between groups. Once clinical reasoning scores were tabulated, the top six and bottom six scorers on clinical reasoning were interviewed to identify qualitative differences between students with different reasoning levels. Themes from the interviews revealed that those with high clinical reasoning reported a high frequency of use of focused reflection and articulation, engaged in abstract learning, and were more self-regulated in their learning than those who scored low on clinical reasoning. This study provides empirical evidence that using instructional methods that focus learners' attention on the concrete application of theory in the practicum setting helps enhance their reasoning skills. PMID:15508561

  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. 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

  19. 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. PMID:23030327

  20. 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

  1. Ultrastructural evidence for the accumulation of insulin in nuclei of intact 3T3-L1 adipocytes by an insulin-receptor mediated process

    SciTech Connect

    Smith, R.M.; Jarett, L.

    1987-01-01

    Monomeric ferritin-labeled insulin (F/sub m/-Ins), a biologically active, electron-dense marker of occupied insulin receptors, was used to characterize the internalization of insulin in 3T3-L1 adipocytes. F/sub m/-Ins bound specifically to insulin receptors and was internalized in a time- and temperature-dependent manner. In the nucleus, several F/sub m/-Ins particles usually were found in the same general location-near nuclear pores, associated with the periphery of the condensed chromatin. Addition of a 250-fold excess of unlabeled insulin or incubation at 15/sup 0/C reduced the number of F/sub m/-Ins particles found in nuclei after 90 min by 99% or 92%, respectively. Nuclear accumulation of unlabeled ferritin was only 2% of that found with F/sub m/-Ins after 90 min at 37/sup 0/C. Biochemical experiments utilizing /sup 125/I-labeled insulin and subcellular fractionation indicated that intact 3T3-L1 adipocytes internalized insulin rapidly and that approx. = 3% of the internalized ligand accumulated in nuclei after 1 hr. These data provide biochemical and high-resolution ultrastructural evidence that 3T3-L1 adipocytes accumulate potentially significant amounts of insulin in nuclei by an insulin receptor-mediated process. The transport of insulin or the insulin-receptor complex to nuclei in this cell or in others may be directly involved in the long-term biological effects of insulin - in particular, in the control of DNA and RNA synthesis.

  2. Azelaic Acid: Evidence-based Update on Mechanism of Action and Clinical Application.

    PubMed

    Schulte, Brian C; Wu, Wesley; Rosen, Ted

    2015-09-01

    Azelaic acid is a complex molecule with many diverse activities. The latter include anti-infective and anti-inflammatory action. The agent also inhibits follicular keratinization and epidermal melanogenesis. Due to the wide variety of biological activities, azelaic acid has been utilized as a management tool in a broad spectrum of disease states and cutaneous disorders. This paper reviews the clinical utility of azelaic acid, noting the quality of the evidence supporting each potential use. PMID:26355614

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

    PubMed

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

    2014-01-01

    The high prevalence of trauma exposure in mental health service-seeking populations, combined with advances in evidence-based practice, competency-based training, common-elements research, and adult learning make this an opportune time to train the mental health workforce in trauma competencies. The Core Curriculum on Childhood Trauma (CCCT) utilizes a five-tiered conceptual framework (comprising Empirical Evidence, Core Trauma Concepts, Intervention Objectives, Practice Elements, and Skills), coupled with problem-based learning, to build foundational trauma knowledge and clinical reasoning skills. We present findings from three studies: Study 1 found that social work graduate students' participation in a CCCT course (N = 1,031) was linked to significant pre-post increases in self-reported confidence in applying core trauma concepts to their clinical work. Study 2 found significant pre-post increases in self-reported conceptual readiness (N = 576) and field readiness (N = 303) among social work graduate students participating in a "Gold Standard Plus" educational model that integrated classroom instruction in core trauma concepts, training in evidence-based trauma treatment (EBTT), and implementation of that EBTT in a supervised field placement. Students ranked the core concepts course as an equivalent or greater contributor to field readiness compared to standard EBTT training. Study 3 used qualitative methods to "distill" common elements (35 intervention objectives, 59 practice elements) from 26 manualized trauma interventions. The CCCT is a promising tool for educating "next-generation" evidence-based practitioners who possess competencies needed to implement modularized, individually tailored trauma interventions by strengthening clinical knowledge, clinical reasoning, and familiarity with common elements. PMID:24484506

  4. 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.

  5. 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.

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

    PubMed Central

    Wang, Wangchen; Yang, Lin; Huang, Huey W.

    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. PMID:17259270

  7. Nitrogen starvation-induced accumulation of triacylglycerol in the green algae: evidence for a role for ROC40, a transcription factor involved in circadian rhythm.

    PubMed

    Goncalves, Elton C; Koh, Jin; Zhu, Ning; Yoo, Mi-Jeong; Chen, Sixue; Matsuo, Takuya; Johnson, Jodie V; Rathinasabapathi, Bala

    2016-03-01

    Microalgal triacylglycerol (TAG), a promising source of biofuel, is induced upon nitrogen starvation (-N), but the proteins and genes involved in this process are poorly known. We performed isobaric tagging for relative and absolute quantification (iTRAQ)-based quantitative proteomics to identify Chlorella proteins with modulated expression under short-term -N. Out of 1736 soluble proteins and 2187 membrane-associated proteins identified, 288 and 56, respectively, were differentially expressed under -N. Gene expression analysis on select genes confirmed the same direction of mRNA modulation for most proteins. The MYB-related transcription factor ROC40 was the most induced protein, with a 9.6-fold increase upon -N. In a previously generated Chlamydomonas mutant, gravimetric measurements of crude total lipids revealed that roc40 was impaired in its ability to increase the accumulation of TAG upon -N, and this phenotype was complemented when wild-type Roc40 was expressed. Results from radiotracer experiments were consistent with the roc40 mutant being comparable to the wild type in recycling membrane lipids to TAG but being impaired in additional de novo synthesis of TAG during -N stress. In this study we provide evidence to support the hypothesis that transcription factor ROC40 has a role in -N-induced lipid accumulation, and uncover multiple previously unknown proteins modulated by short-term -N in green algae. PMID:26920093

  8. 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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2016-01-01

    Extracting evidence of the absence of a target of interest from medical text can be useful in clinical inferencing. The purpose of our study was to develop a natural language processing (NLP) pipelineto identify the presence of indwelling urinary catheters from electronic medical notes to aid in detection of catheter-associated urinary tract infections (CAUTI). Finding clear evidence that a patient does not have an indwelling urinary catheter is useful in making a determination regarding CAUTI. We developed a lexicon of seven core concepts to infer the absence of a urinary catheter. Of the 990,391 concepts extractedby NLP from a large corpus of 744,285 electronic medical notes from 5589 hospitalized patients, 63,516 were labeled as evidence of absence.Human review revealed three primary causes for false negatives. The lexicon and NLP pipeline were refined using this information, resulting in outputs with an acceptable false positive rate of 11%. PMID:27350471

  11. 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. PMID:27581825

  12. Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment.

    PubMed

    Silva Filho, Luiz Vicente Ribeiro Ferreira da; Ferreira, Flavia de Aguiar; Reis, Francisco José Caldeira; Britto, Murilo Carlos Amorim de; 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

  13. 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

  14. Evidence supporting predicted metabolic pathways for Vibrio cholerae: gene expression data and clinical tests

    PubMed Central

    Shi, Jing; Romero, Pedro R.; Schoolnik, Gary K.; Spormann, Alfred M.; Karp, Peter D.

    2006-01-01

    Vibrio cholerae, the etiological agent of the diarrheal illness cholera, can kill an infected adult in 24 h. V.cholerae lives as an autochthonous microbe in estuaries, rivers and coastal waters. A better understanding of its metabolic pathways will assist the development of more effective treatments and will provide a deeper understanding of how this bacterium persists in natural aquatic habitats. Using the completed V.cholerae genome sequence and PathoLogic software, we created VchoCyc, a pathway-genome database that predicted 171 likely metabolic pathways in the bacterium. We report here experimental evidence supporting the computationally predicted pathways. The evidence comes from microarray gene expression studies of V.cholerae in the stools of three cholera patients [D. S. Merrell, S. M. Butler, F. Qadri, N. A. Dolganov, A. Alam, M. B. Cohen, S. B. Calderwood, G. K. Schoolnik and A. Camilli (2002) Nature, 417, 642–645.], from gene expression studies in minimal growth conditions and LB rich medium, and from clinical tests that identify V.cholerae. Expression data provide evidence supporting 92 (53%) of the 171 pathways. The clinical tests provide evidence supporting seven pathways, with six pathways supported by both methods. VchoCyc provides biologists with a useful tool for analyzing this organism's metabolic and genomic information, which could lead to potential insights into new anti-bacterial agents. VchoCyc is available in the BioCyc database collection (). PMID:16682451

  15. Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

    PubMed

    Hung, Chi-Sheng; Chou, Chia-Hung; Liao, Che-Wei; Lin, Yen-Tin; Wu, Xue-Ming; Chang, Yi-Yao; Chen, Ying-Hsien; Wu, Vin-Cent; Su, Ming-Jai; Ho, Yi-Lwun; Chen, Ming-Fong; Wu, Kwan-Dun; Lin, Yen-Hung

    2016-06-01

    Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity. PMID:27113051

  16. 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. PMID:23932854

  17. Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

    PubMed Central

    Duffy, Anne

    2014-01-01

    Objectives To describe key findings relating to the natural history and heterogeneity of bipolar disorder (BD) relevant to the development of a unitary clinical staging model. Currently proposed staging models are briefly discussed, highlighting complementary findings, and a comprehensive staging model of BD is proposed integrating the relevant evidence. Method: A selective review of key published findings addressing the natural history, heterogeneity, and clinical staging models of BD are discussed. Results: The concept of BD has broadened, resulting in an increased spectrum of disorders subsumed under this diagnostic category. Different staging models for BD have been proposed based on the early psychosis literature, studies of patients with established BD, and prospective studies of the offspring of parents with BD. The overarching finding is that there are identifiable sequential clinical phases in the development of BD that differ in important ways between classical episodic and psychotic spectrum subtypes. In addition, in the context of familial risk, early risk syndromes add important predictive value and inform the staging model for BD. Conclusions: A comprehensive clinical staging model of BD can be derived from the available evidence and should consider the natural history of BD and the heterogeneity of subtypes. This model will advance both early intervention efforts and neurobiological research. PMID:25702367

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

    PubMed Central

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

    2013-01-01

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

  19. 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. PMID:26143590

  20. 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.

  1. 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. PMID:26035469

  2. 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

  3. Appraisal of the evidence for the clinical use of FFP and plasma fractions.

    PubMed

    Stanworth, S J; Brunskill, S J; Hyde, C J; Murphy, M F; McClelland, D B L

    2006-01-01

    Randomised, controlled trials of good quality are a recognised means to robustly assess the efficacy of interventions in clinical practice. A systematic identification and appraisal of all randomised trials involving fresh frozen plasma (FFP) indicates that most clinical indications for FFP, as currently recommended by practice guidelines, are not supported by evidence from randomised trials. This chapter will largely consider the implications of some of the findings from this systematic review. Many published trials on the use of FFP have enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials include the dose of FFP used, and the potential for bias; no studies had taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. In addition, there is little evidence for the effectiveness of the prophylactic use of FFP. There is a pressing need to consider how best to develop new trials to determine the effectiveness of FFP. How this can be achieved can be illustrated by reference to studies of albumin in critical care. A recent, large and well-designed randomised trial (Saline versus Albumin Fluid Evaluation study; SAFE) in critical care found no evidence of an increase in mortality with the use of albumin compared to saline, which had been hypothesised in an earlier systematic review. How the study findings will actually now influence the clinical use of albumin remains to be seen. Although the SAFE trial showed no increase in mortality with albumin compared with saline, it is difficult to justify its use in critical care given its considerably greater cost. PMID:16377542

  4. 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. PMID:21601431

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

    PubMed

    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

  6. 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

  7. 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

  8. Evidence-based medicine and values-based medicine: partners in clinical education as well as in clinical practice

    PubMed Central

    2013-01-01

    The best clinical decisions are based on both evidence and values in what is known as the 'two-feet principle'. Anecdotally, educationalists find teaching clinicians to become more evidence based is relatively simple in comparison to encouraging them to become more values based. One reason is likely to be the importance of values awareness. As values-based practice is premised on a mutual respect for the diversity of values, clinicians need to develop the skills to ascertain patient values and to get in touch with their own beliefs and preferences in order to understand those at play in any consultation. Only then can shared decision-making processes take place within a shared framework of values. In a research article published in BMC Medicine, Altamirano-Bustamante and colleagues highlight difficulties that clinicians face in getting in touch with their own values. Despite finding that healthcare personnel's core values were honesty and respect, autonomy was initially low ranked by participants. One significant aspect of this work is that this group has demonstrated that the extent to which clinicians value 'autonomy' and 'openness to change' can both be positively influenced by well designed education. PMID:23414247

  9. Clinical research evidence of cupping therapy in China: a systematic literature review

    PubMed Central

    2010-01-01

    Background Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it. This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies. Methods We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated. Results 550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies. Conclusions According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice. PMID:21078197

  10. 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

  11. Clinical evidence on titanium-zirconium dental implants: a systematic review and meta-analysis.

    PubMed

    Altuna, P; Lucas-Taulé, E; Gargallo-Albiol, J; Figueras-Álvarez, O; Hernández-Alfaro, F; Nart, J

    2016-07-01

    The use of titanium implants is well documented and they have high survival and success rates. However, when used as reduced-diameter implants, the risk of fracture is increased. Narrow diameter implants (NDIs) of titanium-zirconium (Ti-Zr) alloy have recently been developed (Roxolid; Institut Straumann AG). Ti-Zr alloys (two highly biocompatible materials) demonstrate higher tensile strength than commercially pure titanium. The aim of this systematic review was to summarize the existing clinical evidence on dental NDIs made from Ti-Zr. A systematic literature search was performed using the Medline database to find relevant articles on clinical studies published in the English language up to December 2014. Nine clinical studies using Ti-Zr implants were identified. Overall, 607 patients received 922 implants. The mean marginal bone loss was 0.36±0.06mm after 1 year and 0.41±0.09mm after 2 years. The follow-up period ranged from 3 to 36 months. Mean survival and success rates were 98.4% and 97.8% at 1 year after implant placement and 97.7% and 97.3% at 2 years. Narrow diameter Ti-Zr dental implants show survival and success rates comparable to regular diameter titanium implants (>95%) in the short term. Long-term follow-up clinical data are needed to confirm the excellent clinical performance of these implants. PMID:26852292

  12. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    PubMed

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

  13. [Personalised pharmacogenetics. Evidence-based guidelines and clinical application of pharmacogenetic diagnostics].

    PubMed

    Stingl, J C; Brockmöller, J

    2013-11-01

    The broad clinical application of pharmacogenetic diagnostics for individualised drug treatment is still limited. With the exception of oncological therapies where molecular tumor makers are frequently used to decide upon individual drug therapies, pharmacogenetic testing is not generally offered in clinical laboratory diagnostics, because the costs are not covered by general health insurance and it is not evident what consequences the results of a genotyping test may have for the individual drug treatment. Especially in the context of pharmacokinetics, bioequivalence-based concepts have been developed that allow the individual drug dosage or therapy to be adjusted to genetic polymorphisms in drug metabolism, drug transport that affect drug absorption, metabolism and elimination. Pharmacogenetic aspects are increasingly included in the product information (e.g., on its website the FDA lists more than 60 drug labels that include pharmacogenetic information). However, most pharmacogenetic information on drug labels does not give recommendations for clinical decisions to be made based on individual genotypes. This gap is currently being closed by the development of international consortia aiming to base clinical recommendations on the best available evidence by systematic review of the existing data. The Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network (CPIC) is an international community-driven organisation that is developing peer-reviewed, freely available gene/drug guidelines that are published in full at PharmGKB (http://www.pharmgkb.org). The aim of these guidelines is to give therapeutic recommendations such as dose adjustments or suggestions for the choice of an alternative drug in the case of specific genotypes (phenotypes) that predict slow metabolism or transport of drugs or safety risks or risks of therapeutic failure. These guidelines are not mandatory but serve to facilitate the translation of pharmacogenetic

  14. The Clinical Management of Bipolar Disorder: A Review of Evidence-Based Guidelines

    PubMed Central

    Thase, Michael E

    2011-01-01

    Objective: To discuss the criteria used to diagnose the mood episodes that constitute bipolar disorder, the approach to the differential diagnosis of these presentations, and the evidence-based treatments that are currently available. Data Sources: A search for evidence-based guidelines for the diagnosis and treatment of adults with bipolar disorder was performed on May 5, 2010, using the National Guideline Clearinghouse database, the Agency for Healthcare Research and Quality Evidence Reports database, and the Cochrane Database of Systematic Reviews. In addition, a clinical query of the PubMed database (completed March 1, 2010) and searches of drug manufacturers’ Web sites (for unpublished trials) were performed to identify randomized, controlled trials and meta-analyses evaluating strategies to treat resistant depression. Study Selection: Guidelines were selected based on data from randomized, controlled trials; meta-analyses; and well-conducted naturalistic trials that were published since 2005. Data Extraction: Four evidence-based treatment guidelines for bipolar disorder were included. Three were published in 2009: those put forth as part of an Australian project, those of the British Association for Psychopharmacology, and those produced by the International Society for Bipolar Disorders and the Canadian Network for Mood and Anxiety Treatments. The most recent US guidelines are that of the Texas Implementation of Medication Algorithms project, last updated in 2005. Data Synthesis: Recommendations from all 4 guidelines were reviewed and are presented with a focus on using them to improve clinical care. The recommendations with the most agreement and highest level of clinical evidence were as follows: (1) mania should be treated first-line with lithium, divalproex, or an atypical antipsychotic medication; (2) mixed episodes should be treated first-line with divalproex or an atypical antipsychotic; (3) bipolar depression should be treated with quetiapine

  15. Clinical and multimodal imaging characteristics of acute Vogt-Koyanagi-Harada disease unassociated with clinically evident exudative retinal detachment.

    PubMed

    Attia, Sonia; Khochtali, Sana; Kahloun, Rim; Ammous, Dhiaeddine; Jelliti, Bechir; Ben Yahia, Salim; Zaouali, Sonia; Khairallah, Moncef

    2016-02-01

    The purpose of this study was to describe the clinical and multimodal imaging findings in acute Vogt-Koyanagi-Harada (VKH) disease without clinically evident exudative retinal detachment (ERD). We retrospectively reviewed the charts of 18 patients (36 eyes), diagnosed with acute VKH disease without clinically evident ERD. All patients underwent complete ophthalmic examination, fundus photography, optical coherence tomography (OCT), B-scan ultrasonography, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Of 18 patients, twelve (66.7 %) were female and 6 (33.3 %) were male. Mean age was 39 years (range, 23-60). Ten patients had been referred with an erroneous diagnosis of primary optic nerve disorder (8; 44.4 %) or isolated anterior uveitis (2; 11.1 %). Anterior chamber or vitreous inflammatory reaction was noted in 22 eyes (61.1 %), each. Fundus findings included optic disc swelling in 30 eyes (83.3 %), retinal striae in 20 eyes (55.5 %), and yellowish deep lesions in 3 eyes (8.3 %). OCT showed a shallow, localized subclinical ERD in 18 eyes (50 %), and retinal pigment epithelial folds in 23 eyes (63.9 %). B-scan ultrasonography showed diffuse, low- to medium-reflective choroidal thickening in all eyes. FA disclosed delayed choroidal perfusion in at least one eye of all patients (100 %), mild pinpoint leakage in 21 eyes (58.3 %), optic disc hyperfluorescence in 35 eyes (97.2 %) and choroidal folds in 13 eyes (36.1 %). ICGA findings included delayed choroidal perfusion in 24 eyes (66.7 %), decrease in the number of large choroidal vessels in 36 eyes (100 %), fuzzy choroidal vessels in 35 eyes (97.2 %), and hypofluorescent dark dots in 28 eyes (77.8 %). The association of bilateral optic disc edema with retinal striae and intraocular inflammatory reaction highly suggests acute VKH disease. A multimodal imaging approach including fundus photography, OCT, B-scan ultrasonography, FA, and ICGA provides important clues for the definite diagnosis and

  16. 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

  17. Safety of soy-based infant formulas containing isoflavones: the clinical evidence.

    PubMed

    Merritt, Russell J; Jenks, Belinda H

    2004-05-01

    Soy protein has been used in infant feeding in the West for nearly 100 y. Soy protein infant formulas have evolved in this interval to become safe and effective alternatives for infants whose nutritional needs are not met with human milk or formulas based on cow's milk. Modern soy formulas meet all nutritional requirements and safety standards of the Infant Formula Act of 1980. They are commonly used in infants with immunoglobulin E-mediated cow's milk allergy (at least 86% effective), lactose intolerance, galactosemia, and as a vegetarian human milk substitute. Largely as a result of research in animal models, concerns have been voiced regarding isoflavones in soy infant formulas in relation to nutritional adequacy, sexual development, neurobehavioral development, immune function, and thyroid disease. We discuss the available clinical evidence regarding each of these issues. Available evidence from adult human and infant populations indicates that dietary isoflavones in soy infant formulas do not adversely affect human growth, development, or reproduction. PMID:15113975

  18. Neurocognitive mechanisms of figurative language processing--evidence from clinical dysfunctions.

    PubMed

    Thoma, Patrizia; Daum, Irene

    2006-01-01

    The interpretation of proverbs has a long tradition in the assessment of abstract thinking, particularly in schizophrenia. Although the usefulness of proverb interpretation as a diagnostic tool has been questioned over the years, the comprehension of non-literal language nevertheless plays an important role in social interactions. Thus, researchers remain interested in the neurocognitive mechanisms mediating comprehension and use of figurative language. The present paper summarizes and evaluates the evidence from behavioral, lesion and imaging studies including data for compromised figurative language processing derived from clinical populations. One main focus is on studies of figurative language comprehension in schizophrenia. Several theoretical explanations proposed to account for the difficulties schizophrenia patients experience when confronted with figurative language will be addressed. An integration of the evidence from different areas of research is attempted and directions for future investigation are outlined. PMID:17079014

  19. 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. PMID:23159868

  20. 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

  1. 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

  2. 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. PMID:23519068

  3. Integrating the principles of evidence-based practice into clinical practice.

    PubMed

    Klardie, Kathleen A; Johnson, Judith; McNaughton, Molly Ann; Meyers, Wendy

    2004-03-01

    This series of articles illustrates many considerations relevant to the application of clinical practice guidelines (CPGs). This particular column describes the actions of a nurse practitioner (NP) striving to understand the foundations of recommendations that are based largely on expert opinion. Although application of CPGs does not generally require this degree of investigation, it is essential that providers understand the processes used to interpret the basis of recommendations, including the application of the basic statistical concepts, when making decisions about how recommendations apply to individual patient scenarios. Utilizing evidence-based practice when providing patient care requires a range of skills that allows the NP to locate appropriate research evidence, to develop an understanding of the statistics used in interpreting and reporting research, and to evaluate the effects of interventions on patient outcomes. The application of the key concepts of evidenced-based practice within the primary care setting is explored through a hypothetical patient scenario, which was created as the focal point for three articles that illustrate principles of evidence-based practice. The goal of this series of articles is to provide a basic understanding of evidence-based practice and its application in clinical practice. This article explores the use of interventions selected from CPGs and investigates the potential effects of recommended interventions on patient outcomes. Commonly encountered statistical concepts are reviewed, and examples of their application in interpreting and reporting research are demonstrated. The principles of relative risk, relative risk reduction, absolute risk reduction, and numbers needed to treat are described. This review provides the NP with some basic skills to determine both the quality and usefulness of research. PMID:15130064

  4. Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited.

    PubMed

    Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor

    2013-12-01

    Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. PMID:23857712

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

    PubMed

    Steele, Rachel; Tiffin, Paul A

    2014-02-01

    Aims and method To evaluate the feasibility of integrating a clinical librarian (CL) within four mental health teams. A CL was attached to three clinical teams and the Trustwide Psychology Research and Clinical Governance Structure for 12 months. Requests for evidence syntheses were recorded. The perceived impact of individual evidence summaries on staff activities was evaluated using a brief online questionnaire. Results Overall, 82 requests for evidence summaries were received: 50% related to evidence for individual patient care, 23% to generic clinical issues and 27% were on management/corporate topics. In the questionnaires 105 participants indicated that the most common impact on their practice was advice given to colleagues (51 respondents), closely followed by the evidence summaries stimulating new ideas for patient care or treatment (50 respondents). Clinical implications The integration of a CL into clinical and corporate teams is feasible and perceived as having an impact on staff activities. A CL may be able to collate 'personalised evidence' which may enhance individualised healthcare. In some cases the usual concept of a hierarchy of evidence may not easily apply, with case reports providing guidance which may be more applicable than population-based studies. PMID:25237487

  6. Usability of conversational agents by patients with inadequate health literacy: evidence from two clinical trials.

    PubMed

    Bickmore, Timothy W; Pfeifer, Laura M; Byron, Donna; Forsythe, Shaula; Henault, Lori E; Jack, Brian W; Silliman, Rebecca; Paasche-Orlow, Michael K

    2010-01-01

    Embodied Conversational Agents (ECA) are computer-animated characters that simulate face-to-face conversation with patients. These agents can be programmed with best practices in human-human health communication and used for automated health education and behavior change counseling interventions. Evidence is presented from two ongoing clinical trials demonstrating that patients at different levels of health literacy find these agents acceptable and easy to use for automated health communication interventions. Innovative computer interface systems can be used to ensure that inadequate health literacy not serve as a barrier to interventions using health information technology. PMID:20845204

  7. Theoretical Basis, Laboratory Evidence, and Clinical Research of Chemical Surgery of the Cornea: Cross-Linking

    PubMed Central

    da Paz, Amanda C.; Bersanetti, Patrícia A.; Salomão, Marcella Q.; Ambrósio, Renato; Schor, Paulo

    2014-01-01

    Corneal cross-linking (CXL) is increasingly performed in ophthalmology with high success rates for progressive keratoconus and other types of ectasia. Despite being an established procedure, some molecular and clinical aspects still require additional studies. This review presents a critical analysis of some established topics and others that are still controversial. In addition, this review examines new technologies and techniques (transepithelial and ultrafast CXL), uses of corneal CXL including natural products and biomolecules as CXL promoters, and evidence for in vitro and in vivo indirect effectiveness. PMID:25215226

  8. Preclinical and clinical evidence for stem cell therapies as treatment for diabetic wounds.

    PubMed

    Heublein, Hannes; Bader, Augustinus; Giri, Shibashish

    2015-06-01

    Diabetic wounds remain a global unsolved problem and the cost of diabetes-related amputations and diabetic wound treatment is approximately US$3 billion and US$9 billion per year, respectively. Diabetic foot ulcers (DFUs) occur in 15% of all patients with diabetes and precede 84% of all diabetes-related lower leg amputations. Currently, there is no satisfying treatment for these hard-to-heal-wounds. However, as we discuss here, experimental preclinical evidence for the successful use of adult stem cell therapies for diabetic wounds gives new hope for the development of effective treatments for use in the clinic. PMID:25603421

  9. 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. PMID:26325482

  10. Choosing the Right Dental Material and Making Sense of the Options: Evidence and Clinical Recommendations.

    PubMed

    Ali, Zaid; Eliyas, Shiyana; Vere, Joseph William

    2015-09-01

    Decision-making is a fundamental aspect of clinical dentistry. Advances in technology and trends towards more conservative technologies have broadened the options available to patients and dentists, increasing the range of choices and opportunities to restore teeth. With such a broad range of dental materials, there are a number of factors to consider in making an appropriate choice. We present several decision-making dilemmas. Namely; how to restore worn lower anterior teeth, what to consider when replacing crowns, materials to consider when providing cuspal protection for posterior teeth, and finally the issues to consider when selecting a luting cement. The evidence supporting different clinical choices is considered in a discussion of the various dilemmas faced. PMID:26591251

  11. Functional Electrical Stimulation in Spinal Cord Injury: Clinical Evidence Versus Daily Practice.

    PubMed

    Bersch, Ines; Tesini, Stefani; Bersch, Ulf; Frotzler, Angela

    2015-10-01

    Functional electrical stimulation (FES) has clinical evidence in the rehabilitation of patients with spinal cord injury as indicated by several studies. Both inpatients and outpatients benefit from the therapeutic effect of the FES. The application areas are multifaceted and can be customized on the need for patients. This is represented by the individuality of the programmability of the stimulators and the variety of stimulation schedules that are based on the knowledge about the effects of FES on structural and functional level. Nevertheless, looking into daily clinical practice, the use of FES is rather poor. Expenditure of time, complexity of technical equipment, and compliance and acceptance of therapists and patients should be taken into account as limiting factors. PMID:26471135

  12. Complex trauma in children and adolescents: evidence-based practice in clinical settings.

    PubMed

    Lawson, David M; Quinn, Jamie

    2013-05-01

    Complex trauma (CT) results from exposure to severe stressors that occur within the caregiver system or with another presumably responsible adult, are repetitive, and begin in childhood or adolescence. As a result, many of these children and adolescents experience lifelong difficulties related to self-regulation, relationships, psychological symptoms, alterations in attention and consciousness, self-injury, identity, and cognitive distortions. The aims of this article include the following: (a) to examine several representative approaches identified as treatments for children and adolescents exposed to CT with respect to similarities and differences; (b) to examine representative evidence of model effectiveness; (c) to discuss how these approaches are and/or could be implemented in clinical practice; and (d) to suggest research designs that would facilitate greater translation of effective treatment into clinical settings. PMID:23564579

  13. Clinical experiences and current evidence for therapeutic recombinant factor VIIa treatment in nontrauma settings.

    PubMed

    Grounds, R Michael; Bolan, Charles

    2005-01-01

    The hemostatic properties of recombinant activated factor VII (rFVIIa) are established in patients with inherited or acquired hemophilia with inhibitors and in patients with congenital factor VII deficiencies. Emerging clinical evidence suggests that there may be a wider role for rFVIIa in the management of hemorrhage associated with traumatic injury/accident and severe bleeding associated with critical surgery. This article considers recent data from studies in which rFVIIa was used in an attempt to control bleeding in clinical situations as diverse as coagulopathy associated with chronic liver disease, massive perioperative bleeding and bleeding during prostatectomy, organ transplantation and orthopedic surgery, uncontrollable obstetric hemorrhage, and intracerebral hemorrhage. In nontrauma settings involving acute and potentially life threatening bleeding, there may be a place for rFVIIa as adjunctive therapy in the control of hemostasis. PMID:16221317

  14. Direct evidence of "damage accumulation" in cement mantles surrounding femoral hip stems retrieved at autopsy: cement damage correlates with duration of use and BMI.

    PubMed

    Race, A; Miller, M A; Izant, T H; Mann, K A

    2011-09-01

    The "damage accumulation" phenomenon has not been quantitatively demonstrated in clinical cement mantles surrounding femoral hip stems. We stained transverse sections of 11 postmortem retrieved femoral hip components fixed with cement using fluorescent dye-penetrant and quantified cement damage, voids, and cement-bone interface gaps in epifluorescence and white light micrographs. Crack density (Cr.Dn), crack length-density (Cr.Ln.Dn), porosity, and cement-bone interface gap fraction (c/b-gap%) were calculated, normalized by mantle area. Multiple regression tests showed that cement damage (Cr.Ln.Dn. & Cr.Dn.) was significantly positively correlated (r(2)=0.98, p<0.001) with "duration of use" and body mass index ("BMI") but not cement mantle "porosity". There were significant interactions: "duration of use"*"BMI" was strongly predictive (p<0.005) of Cr.Dn.; and "duration of use"*"porosity" was predictive (p=0.04) of Cr.Ln.Dn. Stem related cracks accounted for approximately one fifth of Cr.Dn and one third of Cr.Ln.Dn. The mean c/b-gap% was 13.8% but it did not correlate (r(2)=0.01, p=0.8) with duration of use. We concluded that duration-dependent fatigue damage accumulation occurred during in vivo use. BMI strongly influenced cement crack length and the rate of new crack formation over time. Voids did not increase the rate of crack initiation but appeared to have promoted crack growth over time. Although not progressive, substantial bone resorption at the cement-bone interface appeared to be common. PMID:21802085

  15. 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

  16. 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

  17. 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

    2016-06-01

    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. PMID:27181682

  18. [Acupuncture clinical studies and evidence-based medicine--an update].

    PubMed

    Lao, Li-xing

    2008-02-01

    Acupuncture has been widely used in the West in recent years and demand has been growing for scientific evaluation of its clinical efficacy. The practice of evidence-based medicine has brought new challenges in the design of acupuncture research, and publication of randomized clinical trials on acupuncture has significantly increased. While systematic reviews of these trials have advanced our current knowledge, they have exposed deficiencies in research design and revealed that one design can not answer all research questions. Few clinical studies conducted in China have been published in the West, and most published in Chinese suffer from methodological design flaws that render the results unreliable and unconvincing. Such flaws include inadequate or no randomization, inadequate control, unsatisfactory outcome measurements, lack of proper concealment, insufficient follow-up, and improper statistical analysis. To foster high quality acupuncture clinical research in China, we must cultivate innovation and creativity in research design. It is unwise to simply follow or copy the research methodology of Western pharmaceutical studies. Acupuncture and traditional Chinese medicine (TCM) must be evaluated using rigorous scientific methods that preserve the essence of TCM concepts, so that acupuncture and TCM, these ancient healing arts, can continue to play an important role in the health care systems of modern societies. PMID:18386647

  19. 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

  20. Wiki-Based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma: A New Paradigm in Sarcoma Evidence

    PubMed Central

    Neuhaus, S. J.; Thomas, D.; Desai, J.; Vuletich, C.; von Dincklage, J.; Olver, I.

    2015-01-01

    In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community. PMID:25784832

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

    PubMed

    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

  2. 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

  3. Bisphenol A, Hypertension, and Cardiovascular Diseases: Epidemiological, Laboratory, and Clinical Trial Evidence.

    PubMed

    Han, Changwoo; Hong, Yun-Chul

    2016-02-01

    Bisphenol A (BPA) exposure has become one of the most common environmental chemical exposures in humans. There is growing evidence regarding an association between BPA exposure, hypertension, and cardiovascular diseases (CVD). If BPA exposure is indeed associated with raised blood pressure and CVD, it would be a major public health problem. Therefore, we reviewed the epidemiological, laboratory, and clinical trial evidence for an association between BPA exposure, CVD, and hypertension, and discussed the possible mechanisms in this article. Cross-sectional studies in various ethnicities suggested a possible association between BPA exposure and hypertension; this association was supported by a panel study and a randomized clinical trial. Despite the discordance among cross-sectional studies about an association between BPA exposure and CVD, a longitudinal study shows that BPA exposure is a risk factor for CVD. The effects of BPA exposure such as endocrinal disturbance, induction of oxidative stress and inflammation, epigenetic change, and links with other chronic diseases may highlight a possible mechanism between BPA exposure, CVD, and hypertension. To clarify the causal relationship, well-designed studies are needed in the future. PMID:26781251

  4. Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence

    PubMed Central

    Frajese, Giovanni Vanni; Pozzi, Flavio; Frajese, Gaetano

    2006-01-01

    Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least “typical” PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases. PMID:18046921

  5. Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.

    PubMed

    Koenighofer, M; Hung, C Y; McCauley, J L; Dallman, J; Back, E J; Mihalek, I; Gripp, K W; Sol-Church, K; Rusconi, P; Zhang, Z; Shi, G-X; Andres, D A; Bodamer, O A

    2016-03-01

    RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (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

  6. 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

  7. Enhancement of cognitive and neural functions through complex reasoning training: evidence from normal and clinical populations.

    PubMed

    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

  8. 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

  9. Understanding the impact of economic evidence on clinical decision making: a discrete choice experiment in cardiology.

    PubMed

    Torbica, Aleksandra; Fattore, Giovanni

    2010-05-01

    The present study aims to evaluate the impact of cost-effectiveness information on clinical decision making using discrete choice experiment (DCE) methodology. Data were collected through a self-completed questionnaire administered to Italian cardiologists in June 2007 (n = 129 respondents, 1143 observations). The questionnaire asked clinicians to make choices between paired scenarios, across which three key dimensions were identified and varied: (1) quality of clinical evidence, (2) size of health gain (reduction of relative and absolute risk), and (3) economic impact (incremental cost-effectiveness ratio). A random effects probit model was used to estimate clinicians' preferences for the different dimensions, while the heterogeneity of preferences was tested in a model with interaction terms. Dominance tests were used to assess the consistency of responses. The results indicate that Italian cardiologists regard economic impact (cost-effectiveness) as an important factor in their decision making. Economic evidence is valued more highly among clinicians with a higher self-assessed level of knowledge regarding economic evaluation techniques, as well as among younger professionals (age<45). While relevant study limitations should be acknowledged, our results suggest that DCEs can be used to elicit clinicians' decision-making criteria and to inform the allocation of resources for future research in a logical manner. Italian cardiologists appear to take cost-effectiveness information into account when deciding whether to use new treatments. PMID:20207466

  10. Classification and clinical diagnosis of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines.

    PubMed

    Fitzcharles, Mary-Ann; Shir, Yoram; Ablin, Jacob N; Buskila, Dan; Amital, Howard; Henningsen, Peter; Häuser, Winfried

    2013-01-01

    Objectives. Fibromyalgia syndrome (FMS), characterized by subjective complaints without physical or biomarker abnormality, courts controversy. Recommendations in recent guidelines addressing classification and diagnosis were examined for consistencies or differences. Methods. Systematic searches from January 2008 to February 2013 of the US-American National Guideline Clearing House, the Scottish Intercollegiate Guidelines Network, Guidelines International Network, and Medline for evidence-based guidelines for the management of FMS were conducted. Results. Three evidence-based interdisciplinary guidelines, independently developed in Canada, Germany, and Israel, recommended that FMS can be clinically diagnosed by a typical cluster of symptoms following a defined evaluation including history, physical examination, and selected laboratory tests, to exclude another somatic disease. Specialist referral is only recommended when some other physical or mental illness is reasonably suspected. The diagnosis can be based on the (modified) preliminary American College of Rheumatology (ACR) 2010 diagnostic criteria. Discussion. Guidelines from three continents showed remarkable consistency regarding the clinical concept of FMS, acknowledging that FMS is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms, not explained by another somatic disease. While FMS remains an integral part of rheumatology, it is not an exclusive rheumatic condition and spans a broad range of medical disciplines. PMID:24379886

  11. Classification and Clinical Diagnosis of Fibromyalgia Syndrome: Recommendations of Recent Evidence-Based Interdisciplinary Guidelines

    PubMed Central

    Fitzcharles, Mary-Ann; Shir, Yoram; Ablin, Jacob N.; Buskila, Dan; Henningsen, Peter

    2013-01-01

    Objectives. Fibromyalgia syndrome (FMS), characterized by subjective complaints without physical or biomarker abnormality, courts controversy. Recommendations in recent guidelines addressing classification and diagnosis were examined for consistencies or differences. Methods. Systematic searches from January 2008 to February 2013 of the US-American National Guideline Clearing House, the Scottish Intercollegiate Guidelines Network, Guidelines International Network, and Medline for evidence-based guidelines for the management of FMS were conducted. Results. Three evidence-based interdisciplinary guidelines, independently developed in Canada, Germany, and Israel, recommended that FMS can be clinically diagnosed by a typical cluster of symptoms following a defined evaluation including history, physical examination, and selected laboratory tests, to exclude another somatic disease. Specialist referral is only recommended when some other physical or mental illness is reasonably suspected. The diagnosis can be based on the (modified) preliminary American College of Rheumatology (ACR) 2010 diagnostic criteria. Discussion. Guidelines from three continents showed remarkable consistency regarding the clinical concept of FMS, acknowledging that FMS is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms, not explained by another somatic disease. While FMS remains an integral part of rheumatology, it is not an exclusive rheumatic condition and spans a broad range of medical disciplines. PMID:24379886

  12. Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins.

    PubMed

    Kimata, Yukio; Kimata, Yuki I; Shimizu, Yusuke; Abe, Hiroshi; Farcasanu, Ileana C; Takeuchi, Masato; Rose, Mark D; Kohno, Kenji

    2003-06-01

    In the unfolded protein response (UPR) signaling pathway, accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a transmembrane kinase/ribonuclease Ire1, which causes the transcriptional induction of ER-resident chaperones, including BiP/Kar2. It was previously hypothesized that BiP/Kar2 plays a direct role in the signaling mechanism. In this model, association of BiP/Kar2 with Ire1 represses the UPR pathway while under conditions of ER stress, BiP/Kar2 dissociation leads to activation. To test this model, we analyzed five temperature-sensitive alleles of the yeast KAR2 gene. When cells carrying a mutation in the Kar2 substrate-binding domain were incubated at the restrictive temperature, association of Kar2 to Ire1 was disrupted, and the UPR pathway was activated even in the absence of extrinsic ER stress. Conversely, cells carrying a mutation in the Kar2 ATPase domain, in which Kar2 poorly dissociated from Ire1 even in the presence of tunicamycin, a potent inducer of ER stress, were unable to activate the pathway. Our findings provide strong evidence in support of BiP/Kar2-dependent Ire1 regulation model and suggest that Ire1 associates with Kar2 as a chaperone substrate. We speculate that recognition of unfolded proteins is based on their competition with Ire1 for binding with BiP/Kar2. PMID:12808051

  13. Genetic Evidence for a Role of BiP/Kar2 That Regulates Ire1 in Response to Accumulation of Unfolded Proteins

    PubMed Central

    Kimata, Yukio; Kimata, Yuki I.; Shimizu, Yusuke; Abe, Hiroshi; Farcasanu, Ileana C.; Takeuchi, Masato; Rose, Mark D.; Kohno, Kenji

    2003-01-01

    In the unfolded protein response (UPR) signaling pathway, accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a transmembrane kinase/ribonuclease Ire1, which causes the transcriptional induction of ER-resident chaperones, including BiP/Kar2. It was previously hypothesized that BiP/Kar2 plays a direct role in the signaling mechanism. In this model, association of BiP/Kar2 with Ire1 represses the UPR pathway while under conditions of ER stress, BiP/Kar2 dissociation leads to activation. To test this model, we analyzed five temperature-sensitive alleles of the yeast KAR2 gene. When cells carrying a mutation in the Kar2 substrate-binding domain were incubated at the restrictive temperature, association of Kar2 to Ire1 was disrupted, and the UPR pathway was activated even in the absence of extrinsic ER stress. Conversely, cells carrying a mutation in the Kar2 ATPase domain, in which Kar2 poorly dissociated from Ire1 even in the presence of tunicamycin, a potent inducer of ER stress, were unable to activate the pathway. Our findings provide strong evidence in support of BiP/Kar2-dependent Ire1 regulation model and suggest that Ire1 associates with Kar2 as a chaperone substrate. We speculate that recognition of unfolded proteins is based on their competition with Ire1 for binding with BiP/Kar2. PMID:12808051

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

    PubMed Central

    2014-01-01

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

  15. Factors Associated with Success in Searching medline and Applying Evidence to Answer Clinical Questions

    PubMed Central

    Hersh, William R.; Crabtree, M. Katherine; Hickam, David H.; Sacherek, Lynetta; Friedman, Charles P.; Tidmarsh, Patricia; Mosbaek, Craig; Kraemer, Dale

    2002-01-01

    Objectives: This study sought to assess the ability of medical and nurse practitioner students to use medline to obtain evidence for answering clinical questions and to identify factors associated with the successful answering of questions. Methods: A convenience sample of medical and nurse practitioner students was recruited. After completing instruments measuring demographic variables, computer and searching attitudes and experience, and cognitive traits, the subjects were given a brief orientation to medline searching and the techniques of evidence-based medicine. The subjects were then given 5 questions (from a pool of 20) to answer in two sessions using the Ovid medline system and the Oregon Health & Science University library collection. Each question was answered using three possible responses that reflected the quality of the evidence. All actions capable of being logged by the Ovid system were captured. Statistical analysis was performed using a model based on generalized estimating equations. The relevance-based measures of recall and precision were measured by defining end queries and having relevance judgments made by physicians who were not associated with the study. Results: Forty-five medical and 21 nurse practitioner students provided usable answers to 324 questions. The rate of correctness increased from 32.3 to 51.6 percent for medical students and from 31.7 to 34.7 percent for nurse practitioner students. Ability to answer questions correctly was most strongly associated with correctness of the answer before searching, user experience with medline features, the evidence-based medicine question type, and the spatial visualization score. The spatial visualization score showed multi-collinearity with student type (medical vs. nurse practitioner). Medical and nurse practitioner students obtained comparable recall and precision, neither of which was associated with correctness of the answer. Conclusions: Medical and nurse practitioner students in this

  16. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

    PubMed

    Federici, Silvia; Sormani, Maria Pia; Ozen, Seza; Lachmann, Helen J; Amaryan, Gayane; Woo, Patricia; Koné-Paut, Isabelle; Dewarrat, Natacha; Cantarini, Luca; Insalaco, Antonella; Uziel, Yosef; Rigante, Donato; Quartier, Pierre; Demirkaya, Erkan; Herlin, Troels; Meini, Antonella; Fabio, Giovanna; Kallinich, Tilmann; Martino, Silvana; Butbul, Aviel Yonatan; Olivieri, Alma; Kuemmerle-Deschner, Jasmin; Neven, Benedicte; Simon, Anna; Ozdogan, Huri; Touitou, Isabelle; Frenkel, Joost; Hofer, Michael; Martini, Alberto; Ruperto, Nicolino; Gattorno, Marco

    2015-05-01

    The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed. PMID:25637003

  17. Exploring use of images in clinical articles for decision support in evidence-based medicine

    NASA Astrophysics Data System (ADS)

    Antani, Sameer; Demner-Fushman, Dina; Li, Jiang; Srinivasan, Balaji V.; Thoma, George R.

    2008-01-01

    Essential information is often conveyed pictorially (images, illustrations, graphs, charts, etc.) in biomedical publications. A clinician's decision to access the full text when searching for evidence in support of clinical decision is frequently based solely on a short bibliographic reference. We seek to automatically augment these references with images from the article that may assist in finding evidence. In a previous study, the feasibility of automatically classifying images by usefulness (utility) in finding evidence was explored using supervised machine learning and achieved 84.3% accuracy using image captions for modality and 76.6% accuracy combining captions and image data for utility on 743 images from articles over 2 years from a clinical journal. Our results indicated that automatic augmentation of bibliographic references with relevant images was feasible. Other research in this area has determined improved user experience by showing images in addition to the short bibliographic reference. Multi-panel images used in our study had to be manually pre-processed for image analysis, however. Additionally, all image-text on figures was ignored. In this article, we report on developed methods for automatic multi-panel image segmentation using not only image features, but also clues from text analysis applied to figure captions. In initial experiments on 516 figure images we obtained 95.54% accuracy in correctly identifying and segmenting the sub-images. The errors were flagged as disagreements with automatic parsing of figure caption text allowing for supervised segmentation. For localizing text and symbols, on a randomly selected test set of 100 single panel images our methods reported, on the average, precision and recall of 78.42% and 89.38%, respectively, with an accuracy of 72.02%.

  18. 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…

  19. [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. PMID:26645441

  20. 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. PMID:27213821

  1. 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.

  2. No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate-Mefloquine in Northwestern Brazil.

    PubMed

    Ladeia-Andrade, Simone; de Melo, Gladson Naber P; de Souza-Lima, Rita de Cássia; Salla, Laís C; Bastos, Melissa S; Rodrigues, Priscila T; Luz, Francisco das Chagas O; Ferreira, Marcelo U

    2016-07-01

    We evaluated the clinical efficacy of artesunate-mefloquine (ASMQ) fixed-dose combination to treat uncomplicated malaria in Juruá Valley, the main Plasmodium falciparum transmission hotspot in Brazil. Between November 2010 and February 2013, we enrolled 162 patients aged 4-73 years, with fever or a history of fever, and a single-species P. falciparum infection confirmed by microscopy and polymerase chain reaction (PCR). All 154 patients who completed the 42-day follow-up presented an adequate clinical and parasitologic response. ASMQ was well tolerated and no adverse event caused treatment interruption. Gametocytes were detected in 46.3% patients; 35.2% had gametocytes at enrollment, whereas others developed patent gametocytemia 1-14 days after starting ASMQ. By day 3 of treatment, all subjects had cleared asexual parasitemia, but parasite DNA remained PCR detectable in 37.6% of them. Day-3 PCR positivity was associated with prolonged gametocyte carriage. We found no molecular evidence of resistance to either MQ (pfmdr1 gene amplification) or AS (mutations in selected kelch13 gene domains known to be associated with AS resistance) in the local P. falciparum population. These results strongly support the use of ASMQ as a first-line regimen to treat uncomplicated P. falciparum malaria in northwestern Brazil, but underscore the need for gametocytocidal drugs to reduce the transmission potential of ASMQ-treated patients (ClinicalTrials.gov number NCT01144702). PMID:27068396

  3. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

    PubMed Central

    Henrie, Adam M; Nawarskas, James J; Anderson, Joe R

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phos-phodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH. PMID:26587013

  4. 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. PMID:27063256

  5. Evidence for the criterion validity and clinical utility of the Pathological Narcissism Inventory

    PubMed Central

    Thomas, Katherine M.; Wright, Aidan G.C.; Lukowitsky, Mark R.; Donnellan, M. Brent; Hopwood, Christopher J.

    2012-01-01

    In this study we evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (Ns = 299, 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic vulnerability with established indices of normal personality traits, psychopathology and clinical concerns, and pathological personality traits. Overall, the pattern of correlations supported the convergent and discriminate validity of grandiose and vulnerable conceptualizations of pathological narcissism as measured by the PNI. Clinical utility was assessed by evaluating the extent to which clinicians without specific training in pathological narcissism as well as clinicians with expertise in pathological narcissism could accurately predict the correlates of PNI grandiosity and vulnerability with normal and pathological personality traits and psychopathology. The rcontrast-cv coefficient (Westen & Rosenthal, 2003) provided a global index of accuracy in clinicians’ predictions that was more fully elaborated by examining systematic discrepancies across groups. Overall, novice and expert clinicians were generally able to predict criterion correlations, with some exceptions (e.g., counter to predictions, pathological narcissism was negatively associated with treatment resistance). These results provide further evidence regarding the validity and utility of the narcissistic grandiosity and narcissistic vulnerability constructs as measured by the PNI. PMID:22315481

  6. 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

  7. 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…

  8. 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…

  9. 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

    2015-06-01

    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. PMID:25933054

  10. Predicting analysis time in events-driven clinical trials using accumulating time-to-event surrogate information.

    PubMed

    Wang, Jianming; Ke, Chunlei; Yu, Zhinuan; Fu, Lei; Dornseif, Bruce

    2016-05-01

    For clinical trials with time-to-event endpoints, predicting the accrual of the events of interest with precision is critical in determining the timing of interim and final analyses. For example, overall survival (OS) is often chosen as the primary efficacy endpoint in oncology studies, with planned interim and final analyses at a pre-specified number of deaths. Often, correlated surrogate information, such as time-to-progression (TTP) and progression-free survival, are also collected as secondary efficacy endpoints. It would be appealing to borrow strength from the surrogate information to improve the precision of the analysis time prediction. Currently available methods in the literature for predicting analysis timings do not consider utilizing the surrogate information. In this article, using OS and TTP as an example, a general parametric model for OS and TTP is proposed, with the assumption that disease progression could change the course of the overall survival. Progression-free survival, related both to OS and TTP, will be handled separately, as it can be derived from OS and TTP. The authors seek to develop a prediction procedure using a Bayesian method and provide detailed implementation strategies under certain assumptions. Simulations are performed to evaluate the performance of the proposed method. An application to a real study is also provided. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26689725

  11. Randomised controlled trial of clinical decision support tools to improve learning of evidence based medicine in medical students

    PubMed Central

    Leung, Gabriel M; Johnston, Janice M; Tin, Keith Y K; Wong, Irene O L; Ho, Lai-Ming; Lam, Wendy W T; Lam, Tai-Hing

    2003-01-01

    Objective To assess the educational effectiveness on learning evidence based medicine of a handheld computer clinical decision support tool compared with a pocket card containing guidelines and a control. Design Randomised controlled trial. Setting University of Hong Kong, 2001. Participants 169 fourth year medical students. Main outcome measures Factor and individual item scores from a validated questionnaire on five key self reported measures: personal application and current use of evidence based medicine; future use of evidence based medicine; use of evidence during and after clerking patients; frequency of discussing the role of evidence during teaching rounds; and self perceived confidence in clinical decision making. Results The handheld computer improved participants' educational experience with evidence based medicine the most, with significant improvements in all outcome scores. More modest improvements were found with the pocket card, whereas the control group showed no appreciable changes in any of the key outcomes. No significant deterioration was observed in the improvements even after withdrawal of the handheld computer during an eight week washout period, suggesting at least short term sustainability of effects. Conclusions Rapid and convenient access to valid and relevant evidence on a portable computing device can improve learning in evidence based medicine, increase current and future use of evidence, and boost students' confidence in clinical decision making. PMID:14604933

  12. 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

  13. 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

  14. Left and right ventricular diastolic functions in patients with rheumatoid arthritis without clinically evident cardiovascular disease.

    PubMed

    Rexhepaj, N; Bajraktari, G; Berisha, I; Beqiri, A; Shatri, F; Hima, F; Elezi, S; Ndrepepa, G

    2006-06-01

    The aim of this study was to assess the prevalence of diastolic dysfunction of the left ventricle (LV) and of the right ventricle in patients with rheumatoid arthritis (RA) without clinically evident cardiovascular manifestations and to estimate whether there is a correlation between the duration of RA and the degree of LV diastolic dysfunction. The study included 81 patients (61 females and 20 males) with RA without clinically evident heart disease (group 1) and 40 healthy subjects (29 females and 11 males) who served as a control group (group 2). Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects. There were significant differences between patients with RA vs. control group with regard to early diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/- 0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13 cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively). There was significant difference between groups regarding the right ventricular early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs. 1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance index (MPI) appeared to differ little in patients with RA as compared with control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA without clinically evident cardiovascular disease, the left ventricular diastolic function and the right ventricular diastolic function are reduced. Left ventricular wall thickness, dimensions, systolic function and MPI were found to be normal. LV diastolic function had a weak correlation with the duration of RA. PMID:16805753

  15. 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…

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

    PubMed Central

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

    2008-01-01

    Summary 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. PMID:18840865

  17. [Role of health-related quality of life in clinical practice: subjectivity in evidence].

    PubMed

    Martí, Camelia; Santos, Alicia; Ybarra, Juan; Martínez, María Antonia; Resmini, Eugenia; Roig, Olga; Webb, Susan M; José Barahona, M

    2009-01-01

    The incorporation of subjective elements provided by the patient to medical practice constitutes a new bridge between two historical movements of human culture: naturalism and rationalism. In recent years, medical sciences have identified these movements as patient-centered medicine and evidence-based medicine. By revisiting the paradigms of medicine, theories of causality, doctor-patient relationship models, bioethical principles and examples of clinical studies, their role and meaning has been revised. The applicability for neuroendocrinology has been demonstrated by validating therapeutic results with measurement of health-related quality of life. The need to incorporate the patient's subjective perception poses a challenge that, when accepted, can advance the understanding and care of human beings--ultimately rational, thinking subjects, and therefore subjective--as our species has been defined. PMID:19695514

  18. Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies.

    PubMed

    Thiboutot, Diane M; Gollnick, Harald P

    2006-09-01

    Acne vulgaris is an exceptionally common, chronic, and recurring disease. It involves multiple etiological factors including follicular hyperkeratinization, increased sebum production, Propionibacterium acnes proliferation, and inflammation. Presently, oral isotretinoin is the only single agent that is effective against all 4 major pathophysiologic features. However, this drug is also responsible for several serious side effects, including teratogenicity. Therefore, it should be used in only the most severe cases and alternative treatment approaches for inflammatory acne, such as initial combination therapy, should be considered first. Combination therapy in inflammatory acne simultaneously targets multiple pathogenic factors. Current guidelines recommend early initiation of combination therapy with a topical retinoid and antimicrobials for mild to moderate inflammatory acne and topical retinoids with oral antibiotics (with or without the use of benzoyl peroxide) for moderate to severe cases of acne, followed by maintenance therapy with topical retinoids. This review evaluates the rationale and clinical evidence for the use of adapalene in combination therapy for inflammatory acne. PMID:16989194

  19. Naturalistic Outcomes of Evidence-Based Therapies for Borderline Personality Disorder at a Medical University Clinic.

    PubMed

    Gregory, Robert J; Sachdeva, Shilpa

    2016-01-01

    Dialectical behavior therapy (DBT) and dynamic deconstructive psychotherapy (DDP) are listed in the National Registry of Evidence-Based Programs and Practices based on their performances in randomized controlled trials. However, little is known about their effectiveness in real-world settings. In the present study, the authors observed the naturalistic outcomes of 68 clients with borderline personality disorder (BPD) who were treated at a medical university clinic by experienced therapists using either comprehensive DBT (n = 25) or DDP (n = 27), with 16 clients treated with unstructured psychotherapy serving as a control. We found both DBT and DDP achieved significant reductions in symptoms of BPD, depression, and disability by 12 months of treatment, and showed effect sizes consistent with controlled trials. However, attrition from DBT was high and DDP obtained better outcomes than DBT (d = .53). Larger effectiveness studies are needed to replicate these findings, delineate common and unique treatment processes, and determine therapist and patient characteristics predicting positive outcomes. PMID:27329405

  20. 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

  1. Atypical femoral fractures and bisphosphonate use: current evidence and clinical implications

    PubMed Central

    Saita, Yoshitomo; Kaneko, Kazuo

    2015-01-01

    Osteoporosis is a disease characterized by a low bone volume and deterioration of the bone quality, which increases the risk of low-energy fractures. Bisphosphonate (BP) treatment increases the bone mass and reduces the risk of fractures in patients with osteoporosis by suppressing bone resorption. In spite of its clinical benefits, the long-term use of BPs has been linked to the occurrence of atypical femoral fractures (AFFs). Although the evidence had been controversial regarding the association between the occurrence of AFFs and BP use, more recent studies with radiographic adjudication have indicated the significant associations between them. However, the pathogenesis of AFFs is not completely understood. The most popular hypothesis has suggested that the suppression of bone turnover by BPs is responsible; however, some recent reports have implied the involvement of pathophysiological alterations of the bone quality and fracture repair process. In this review, we summarize and discuss the epidemiology, risk factors and pathology of AFFs. PMID:26137208

  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. PMID:23845744

  3. Ultrasonographic identification of the cricothyroid membrane: best evidence, techniques, and clinical impact.

    PubMed

    Kristensen, M S; Teoh, W H; Rudolph, S S

    2016-09-01

    Inability to identify the cricothyroid membrane by inspection and palpation contributes substantially to the high failure rate of cricothyrotomy. This narrative review summarizes the current evidence for application of airway ultrasonography for identification of the cricothyroid membrane compared with the clinical techniques. We identified the best-documented techniques for bedside use, their success rates, and the necessary training for airway-ultrasound-naïve clinicians. After a short but structured training, the cricothyroid membrane can be identified using ultrasound in difficult patients by previously airway-ultrasound naïve anaesthetists with double the success rate of palpation. Based on the literature, we recommend identifying the cricothyroid membrane before induction of anaesthesia in all patients. Although inspection and palpation may suffice in most patients, the remaining patients will need ultrasonographic identification; a service that we should aim at making available in all locations where anaesthesia is undertaken and where patients with difficult airways could be encountered. PMID:27432055

  4. 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

  5. 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. PMID:27467312

  6. Atypical femoral fractures and bisphosphonate use: current evidence and clinical implications.

    PubMed

    Saita, Yoshitomo; Ishijima, Muneaki; Kaneko, Kazuo

    2015-07-01

    Osteoporosis is a disease characterized by a low bone volume and deterioration of the bone quality, which increases the risk of low-energy fractures. Bisphosphonate (BP) treatment increases the bone mass and reduces the risk of fractures in patients with osteoporosis by suppressing bone resorption. In spite of its clinical benefits, the long-term use of BPs has been linked to the occurrence of atypical femoral fractures (AFFs). Although the evidence had been controversial regarding the association between the occurrence of AFFs and BP use, more recent studies with radiographic adjudication have indicated the significant associations between them. However, the pathogenesis of AFFs is not completely understood. The most popular hypothesis has suggested that the suppression of bone turnover by BPs is responsible; however, some recent reports have implied the involvement of pathophysiological alterations of the bone quality and fracture repair process. In this review, we summarize and discuss the epidemiology, risk factors and pathology of AFFs. PMID:26137208

  7. 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

  8. 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. PMID:26457655

  9. 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. PMID:24720939

  10. 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

  11. Review of toluene action: clinical evidence, animal studies and molecular targets

    PubMed Central

    Cruz, Silvia L.; Rivera-García, María Teresa; Woodward, John J.

    2014-01-01

    It has long been known that individuals will engage in voluntary inhalation of volatile solvents for their rewarding effects. However, research into the neurobiology of these agents has lagged behind that of more commonly used drugs of abuse such as psychostimulants, alcohol and nicotine. This imbalance has begun to shift in recent years as the serious effects of abused inhalants, especially among children and adolescents, on brain function and behavior have become appreciated and scientifically documented. In this review, we discuss the physicochemical and pharmacological properties of toluene, a representative member of a large class of organic solvents commonly used as inhalants. This is followed by a brief summary of the clinical and pre-clinical evidence showing that toluene and related solvents produce significant effects on brain structures and processes involved in the rewarding aspects of drugs. This is highlighted by tables highlighting toluene’s effect on behaviors (reward, motor effects, learning, etc.) and cellular proteins (e.g. voltage and ligand-gated ion channels) closely associated the actions of abused substances. These sections demonstrate not only the significant progress that has been made in understanding the neurobiological basis for solvent abuse but also reveal the challenges that remain in developing a coherent understanding of this often overlooked class of drugs of abuse. PMID:25360325

  12. 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. PMID:27076499

  13. Cisplatin-Induced Antitumor Immunomodulation: A Review of Preclinical and Clinical Evidence

    PubMed Central

    de Biasi, Andreas R.; Villena-Vargas, Jonathan; Adusumilli, Prasad S.

    2014-01-01

    Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (1) MHC class I expression upregulation; (2) recruitment and proliferation of effector cells; (3) upregulation of the lytic activity of cytotoxic effectors; and (4) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy’s antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy. PMID:25204552

  14. Targeting gut-liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence.

    PubMed

    Federico, Alessandro; Dallio, Marcello; Godos, Justyna; Loguercio, Carmela; Salomone, Federico

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is widely emerging as the most prevalent liver disorder and is associated with increased risk of liver-related and cardiovascular mortality. Recent experimental and clinical studies have revealed the pivotal role played by the alteration of gut-liver axis in the onset of fatty liver and related metabolic disturbances. Gut-liver cross talk is implicated not only in the impairment of lipid and glucose homeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis, which characterize nonalcoholic steatohepatitis (NASH), the evolving form of NAFLD. The gut microbiota has been recognized as the key player in the gut-liver liaison and because of its complexity can act as a villain or a victim. Gut microbiota not only influences absorption and disposal of nutrients to the liver, but also conditions hepatic inflammation by supplying toll-like receptor ligands, which can stimulate liver cells to produce proinflammatory cytokines. Thus, the modification of intestinal bacterial flora by specific probiotics has been proposed as a therapeutic approach for the treatment of NASH. In this review, we summarized the evidence regarding the role of gut-liver axis in the pathogenesis of NASH and discussed the potential therapeutic role of gut microbiota modulation in the clinical setting. PMID:26318867

  15. Utilization of evidence-based psychotherapies in Veterans Affairs posttraumatic stress disorder outpatient clinics

    PubMed Central

    Finley, Erin P.; Garcia, Hector A.; Ketchum, Norma S.; McGeary, Donald D.; McGeary, Cindy A.; Stirman, Shannon Wiltsey; Peterson, Alan L.

    2014-01-01

    In response to the growing numbers of veterans with posttraumatic stress disorder (PTSD), the Department of Veterans Affairs (VA) has sought to make evidence-based psychotherapies for PTSD available at every VA facility. We conducted a national survey of providers within VA PTSD clinical teams (PCTs) to describe utilization of Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) and to identify individual and organizational factors associated with treatment uptake and adherence. Participants (N = 128) completed an electronic survey assessing reported utilization of PE and CPT treatments, adherence to treatment manuals, and characteristics of the provider and workplace environment. Participants reported conducting a weekly mean of 4.5 hours of PE, 3.9 hours of CPT (individual format), 1.3 hours of CPT (group format), and 13.4 hours of supportive care. Perceived effectiveness of PE and CPT were significantly associated with utilization of and adherence to those treatments. Reported number of hours conducting supportive care was positively associated with feeling the clinic was not sufficiently staffed (p = .05). Adherence to the PE treatment manual was positively associated with receiving emotional support from co-workers (p<.01). Provider attitudes and organizational factors such as staffing and work relationships may have an important impact on treatment selection and the quality of PTSD care provided in VA PCTs. PMID:25419915

  16. 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

  17. Viral Immune Evasion in Dengue: Toward Evidence-Based Revisions of Clinical Practice Guidelines

    PubMed Central

    Chiappelli, Francesco; Santos, Silvana Maria Eloi; Caldeira Brant, Xenia Maria; Bakhordarian, Andre; Thames, April D; Maida, Carl A; Du, Angela M; Jan, Allison L; Nahcivan, Melissa; Nguyen, Mia T; Sama, Nateli

    2014-01-01

    Dengue, a leading cause of illness and death in the tropics and subtropics since the 1950׳s, is fast spreading in the Western hemisphere. Over 30% of the world׳s population is at risk for the mosquitoes that transmit any one of four related Dengue viruses (DENV). Infection induces lifetime protection to a particular serotype, but successive exposure to a different DENV increases the likelihood of severe form of dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Prompt supportive treatment lowers the risk of developing the severe spectrum of Dengue-associated physiopathology. Vaccines are not available, and the most effective protective measure is to prevent mosquito bites. Here, we discuss selected aspects of the syndemic nature of Dengue, including its potential for pathologies of the central nervous system (CNS). We examine the fundamental mechanisms of cell-mediated and humoral immunity to viral infection in general, and the specific implications of these processes in the regulatory control of DENV infection, including DENV evasion from immune surveillance. In line with the emerging model of translational science in health care, which integrates translational research (viz., going from the patient to the bench and back to the patient) and translational effectiveness (viz., integrating and utilizing the best available evidence in clinical settings), we examine novel and timely evidence-based revisions of clinical practice guidelines critical in optimizing the management of DENV infection and Dengue pathologies. We examine the role of tele-medicine and stakeholder engagement in the contemporary model of patient centered, effectiveness-focused and evidence-based health care. Abbreviations BBB - blood-brain barrier, CNS - central nervous system, DAMP - damage-associated molecular patterns, DENV - dengue virus, DF - dengue fever, DHF - dengue hemorrhagic fever, DSS - dengue shock syndrome, DALYs - isability adjusted life years, IFN

  18. Cannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention.

    PubMed

    Mizrachi Zer-Aviv, Tomer; Segev, Amir; Akirav, Irit

    2016-10-01

    There is substantial evidence from studies in humans and animal models for a role of the endocannabinoid system in the control of emotional states. Several studies have shown an association between exposure to trauma and substance use. Specifically, it has been shown that there is increased prevalence of cannabis use in post-traumatic stress disorder (PTSD) patients and vice versa. Clinical studies suggest that PTSD patients may cope with their symptoms by using cannabis. This treatment-seeking strategy may explain the high prevalence of cannabis use among individuals with PTSD. Preliminary studies in humans also suggest that treatment with cannabinoids may decrease PTSD symptoms including sleep quality, frequency of nightmares, and hyperarousal. However, there are no large-scale, randomized, controlled studies investigating this specifically. Studies in animal models have shown that cannabinoids can prevent the effects of stress on emotional function and memory processes, facilitate fear extinction, and have an anti-anxiety-like effect in a variety of tasks. Moreover, cannabinoids administered shortly after exposure to a traumatic event were found to prevent the development of PTSD-like phenotype. In this article, we review the existing literature on the use of cannabinoids for treating and preventing PTSD in humans and animal models. There is a need for large-scale clinical trials examining the potential decrease in PTSD symptomatology with the use of cannabis. In animal models, there is a need for a better understanding of the mechanism of action and efficacy of cannabis. Nevertheless, the end result of the current clinical and preclinical data is that cannabinoid agents may offer therapeutic benefits for PTSD. PMID:27551883

  19. Lipid-lowering therapies, glucose control and incident diabetes: evidence, mechanisms and clinical implications.

    PubMed

    Zafrir, Barak; Jain, Mohit

    2014-08-01

    Lipid-lowering therapies constitute an essential part in the treatment and prevention of cardiovascular diseases and are consistently shown to reduce adverse cardiovascular outcomes in wide-scale populations. Recently, there is increased awareness of the possibility that lipid-lowering drugs may affect glucose control and insulin resistance. This phenomenon is reported in all classes of lipid-modifying agents, with differential effects of distinct drugs. Since the prevalence of metabolic syndrome and diabetes is rising, and lipid-modifying therapies are widely used to reduce the cardiovascular burden in these populations, it is of importance to examine the relationship between lipid-lowering drugs, glycemic control and incident diabetes. In the current review we discuss the evidence, ranging from experimental studies to randomized controlled clinical trials and meta-analyses, of how lipid-modifying therapies affect glycemic control and insulin sensitivity. Cumulative data suggest that both statins and niacin are associated with increased risk of impaired glucose control and development of new-onset diabetes, as opposed to bile-acid sequestrants which display concomitant moderate lipid and glucose lowering effects, and fibrates (particularly the pan-PPAR agonist bezafibrate) which may produce beneficial effects on glucose metabolism and insulin sensitivity. Ezetimibe is implied to ameliorate metabolic markers such as hepatic steatosis and insulin resistance, with yet little support from clinical trials, while fish oils which in experimental studies produce favorable effects on insulin sensitivity, although studied extensively, continue to show inconclusive effects on glucose homeostasis in patients with diabetes. Suggested mechanisms of how lipid-modifying agents affect glucose control and their clinical implications in this context, are summarized. PMID:24952127

  20. 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

  1. 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

  2. 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

  3. Clinical Team Functioning and IT Innovation: A Study of the Diffusion of a Point-of-care Online Evidence System

    PubMed Central

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

    2003-01-01

    Objectives: To investigate the association between clinical team functioning and diffusion (awareness, use, and impact) of a 24-hour online evidence retrieval system. To examine the relationships between clinical team characteristics and the adoption of the online evidence system. Design: 18 clinical teams, consisting of 180 clinicians from three Australian hospitals, were identified and studied. Teams were categorized as small (≤ 15 members) or large (> 15). Measurements: Clinical team functioning was assessed using the Team Climate Inventory (TCI). Awareness, use, and impact of an online evidence retrieval system were measured using a self-administered questionnaire. The relationships between TCI scores and awareness, use, and impact were examined using t-tests and one-way ANOVAs. Chi square analyses were used to examine differences between small and large teams. Results were interpreted within a diffusion of innovations framework. Results: Clinical team functioning was not related to awareness or use of the online evidence retrieval system. However, clinical team functioning was significantly associated with the impact of online evidence in terms of reported experience of improved patient care following system use. Clinicians in small teams (≤ 15 members) had higher levels of system awareness compared to large (> 15) teams. Conclusions: Team functioning had the greatest impact on the fourth stage of innovation diffusion, the effective use of online evidence for clinical care. This supports Rogers’ diffusion of innovation theory, to the effect that different types of communication about an innovation are important at different stages in the diffusion process. Members of small teams were more aware of the system than members of large teams. Team functioning is amenable to improvement through interventions. The findings suggest that the role of team climate in the diffusion of information systems is a promising area for future research. PMID:12626379

  4. 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

  5. The clinical effects of red blood cell transfusions: an overview of the randomized controlled trials evidence base.

    PubMed

    Wilkinson, Kirstin L; Brunskill, Susan J; Dorée, Carolyn; Hopewell, Sally; Stanworth, Simon; Murphy, Mike F; Hyde, Chris

    2011-04-01

    No up-to-date overview of randomized controlled trials (RCTs) in red blood cell (RBC) transfusion exists. This systematic review examines the quantity and quality of the evidence for the clinical effects of RBC transfusion. One hundred forty-two eligible RCTs were identified through searches of The Cochrane Library (issue 4, 2009), MEDLINE (1950 to November 2009), EMBASE (1974 to November 2009), and other relevant sources. After data extraction and methodological quality assessment, trials were grouped by clinical specialty and type of RBC transfusion. Data analysis was predominantly descriptive. The 142 RCTs covered 11 specialties and 10 types of RBC transfusion. The number of included patients varied widely across the RCTs (median, 57; IQ range, 27-167). Most trials were single center comparing 2 parallel study arms. Overall, the reporting of methodological assessment was poor, although it improved markedly from 2001. Clinical areas with few trials are highlighted. Comparison with a study of RBC use in clinical practice highlighted a lack of correlation between the size of the evidence base for a given clinical specialty and the proportion of total RBC use by that clinical specialty. The gaps in the evidence base and the poor methodology of trials particularly in the past do not provide a strong evidence base for the use of RBC transfusions, but they indicate important targets for future research. PMID:21345644

  6. 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

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

    PubMed Central

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

    2012-01-01

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

  8. 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

  9. Concordance between Clinical Practice and Published Evidence: Findings from The National Dental Practice-Based Research Network

    PubMed Central

    Norton, Wynne E.; Funkhouser, Ellen; Makhija, Sonia K.; Gordan, Valeria V.; Bader, James D.; Rindal, D. Brad; Pihlstrom, Daniel J.; Hilton, Thomas J.; Frantsve-Hawley, Julie; Gilbert, Gregg H.

    2013-01-01

    Background. Documenting the gap between what is occurring in clinical practice and what published research suggests is an important step toward improving care. This study quantified concordance between clinical practice and published evidence across preventive, diagnostic and treatment procedures among a sample of dentists in the National Dental Practice-Based Research Network. Methods. Network dentists completed one questionnaire about their demographic characteristics and another about how they treat patients across 12 scenarios/clinical practice behaviors. Responses to each clinical practice were coded as consistent (i.e., ‘1’) or inconsistent (i.e., ‘0’) with published evidence, summed, and divided by the number of all non-missing to create an overall ‘concordance’ score, calculated as the mean percent of responses that were consistent with published evidence. Results. Analyses were limited to participants in the United States (N = 591). Mean concordance at the practitioner level was 62% (SD = 18); procedure-specific concordance ranged from 8-100%. Affiliation with a large group practice, being a female practitioner, and receiving a dental degree before 1990 were independently associated with high concordance (≥75%). Conclusions. Dentists reported a medium-range concordance between practice and evidence. Clinical Implications. Efforts to bring research findings into routine practice are needed. PMID:24379327

  10. 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

  11. Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

    PubMed Central

    Lottridge, Danielle M; Chignell, Mark; Danicic-Mizdrak, Romana; Pavlovic, Nada J; Kushniruk, Andre; Straus, Sharon E

    2007-01-01

    Background To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices. Methods Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies. Results 47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012). Conclusion Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization. PMID:17655759

  12. 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. PMID:15475134

  13. Evidence of Blood Stage Efficacy with a Virosomal Malaria Vaccine in a Phase IIa Clinical Trial

    PubMed Central

    Thompson, Fiona M.; Porter, David W.; Okitsu, Shinji L.; Westerfeld, Nicole; Vogel, Denise; Todryk, Stephen; Poulton, Ian; Correa, Simon; Hutchings, Claire; Berthoud, Tamara; Dunachie, Susanna; Andrews, Laura; Williams, Jack L.; Sinden, Robert; Gilbert, Sarah C.; Pluschke, Gerd; Zurbriggen, Rinaldo; Hill, Adrian V. S.

    2008-01-01

    Background Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle. Methods This was a Phase I/IIa study of a new combination malaria vaccine FFM ME-TRAP+PEV3A. PEV3A includes peptides from both the pre-erythrocytic circumsporozoite protein and the blood-stage antigen AMA-1. This study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. The participants were healthy, malaria naïve volunteers, from Oxford. The interventions were vaccination with PEV3A alone, or PEV3A+FFM ME-TRAP. The main outcome measure was protection from malaria in a sporozoite challenge model. Other outcomes included measures of parasite specific immune responses induced by either vaccine; and safety, assessed by collection of adverse event data. Results We observed evidence of blood stage immunity in PEV3A vaccinated volunteers, but no volunteers were completely protected from malaria. PEV3A induced high antibody titres, and antibodies bound parasites in immunofluorescence assays. Moreover, we observed boosting of the vaccine-induced immune response by sporozoite challenge. Immune responses induced by FFM ME-TRAP were unexpectedly low. The vaccines were safe, with comparable side effect profiles to previous trials. Although there was no sterile protection two major observations support an effect of the vaccine-induced response on blood stage parasites: (i) Lower rates of parasite growth were observed in volunteers vaccinated with PEV3A compared to unvaccinated controls (p = 0.012), and this was reflected in the PCR results from PEV3A vaccinated volunteers. These showed early control of parasitaemia by some volunteers in this

  14. 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. PMID:26879862

  15. Clinical characteristics of 53 dogs with Doppler-derived evidence of pulmonary hypertension: 1992-1996.

    PubMed

    Johnson, L; Boon, J; Orton, E C

    1999-01-01

    Pulmonary hypertension occurs as a primary or secondary disorder of the pulmonary vasculature. Doppler echocardiography provides a noninvasive tool for the estimation of pulmonary arterial pressure when tricuspid regurgitation or pulmonic insufficiency is present. The cardiology database at Colorado State University was reviewed, and echocardiographic records from cases diagnosed with pulmonary hypertension were evaluated. Application of the modified Bernoulli equation to the maximal instantaneous velocity of a right-sided regurgitant jet provided evidence of pulmonary hypertension in 53 dogs over a 4-year period. Tricuspid regurgitant velocity > or = 2.8 m/second or pulmonic insufficiency velocity > or = 2.2 m/second was considered abnormal and indicative of pulmonary hypertension. Tricuspid regurgitant gradients in 51 dogs ranged from 32 to 145 mm Hg (mean, 63.0 mm Hg; median, 57.0 mm Hg; 25th-75th percentiles, 45.2-76.5 mm Hg). Pulmonic insufficiency gradients in 8 dogs ranged from 20 to 100 mm Hg (mean, 59.5 mm Hg; median, 61.5 mm Hg; 25th-75th percentiles, 32.0-84.5 mm Hg). Affected dogs ranged in age from 2 months to 16 years. Clinical signs were characteristic of cardiopulmonary disease, but a relatively high frequency of syncope was noted (12 of 53 dogs, 23%). Pulmonary hypertension was probably due to increased pulmonary vascular resistance in 23 dogs, pulmonary overcirculation in 2 dogs, and pulmonary venous hypertension in 23 dogs. Five dogs lacked a clinically recognizable cardiopulmonary cause of pulmonary vascular disease. Our results suggest that pulmonary hypertension can occur as a complication of commonly encountered cardiopulmonary diseases, and that Doppler echocardiography can facilitate recognition of this condition. PMID:10499728

  16. 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

  17. Ultrasonographic evaluation of relative gastrointestinal layer thickness in cats without clinical evidence of gastrointestinal tract disease.

    PubMed

    Winter, Matthew D; Londono, Leonel; Berry, Clifford R; Hernandez, Jorge A

    2014-02-01

    The objectives of this study were (1) to measure normal thickness values of the muscularis, submucosal, mucosal and serosal layers in each gastrointestinal (GI) segment (gastric fundus, body and pyloric antrum; duodenum; jejunum; ileum; colon), and (2) to calculate a ratio of muscularis and mucosal layer thickness to aortic diameter measured at the level of the celiac artery (Musc:Ao and Muc:Ao) in each GI segment in a sample of healthy cats. Ultrasonographic examination of the GI tract was performed, and measurements of the individual layers in each GI segment were obtained in 38 healthy cats without clinical evidence of disease. The muscularis layer was significantly thickest in the ileum, compared with other segments, and it was thicker than the submucosa in all segments except the colon. The mucosa was the thickest layer in all segments, and was thickest in the duodenum and ileum. Measurements of the submucosal and serosal layers were not significantly different between all segments. Musc:Ao and Muc:Ao in each segment were 0.12 and 0.25 (gastric fundus), 0.12 and 0.18 (gastric body), 0.11 and 0.16 (pyloric antrum), 0.08 and 0.27 (duodenum), 0.08 and 0.22 (jejunum), 0.14 and 0.25 (ileum), and 0.05 and 0.08 (colon), respectively. Musc:Ao and Muc:Ao are clinically relevant values that can be used to objectively identify thickening of the muscularis and mucosal layers in response to GI diseases. PMID:23906704

  18. 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

  19. Transanal total mesorectal excision: a systematic review of the experimental and clinical evidence.

    PubMed

    Araujo, S E; Crawshaw, B; Mendes, C R; Delaney, C P

    2015-02-01

    Achieving a clear distal or circumferential resection margins with laparoscopic total mesorectal excision (TME) may be laborious, especially in obese males and when operating on advanced distal rectal tumors with a poor response to neoadjuvant treatment. Transanal (TaTME) is a new natural orifice translumenal endoscopic surgery modality in which the rectum is mobilized transanally using endoscopic techniques with or without laparoscopic assistance. We conducted a comprehensive systematic review of publications on this new technique in PubMed and Embase databases from January, 2008, to July, 2014. Experimental and clinical studies written in English were included. Experimental research with TaTME was done on pigs with and without survival models and on human cadavers. In these studies, laparoscopic or transgastric assistance was frequently used resulting in an easier upper rectal dissection and in a longer rectal specimen. To date, 150 patients in 16 clinical studies have undergone TaTME. In all but 15 cases, transabdominal assistance was used. A rigid transanal endoscopic operations/transanal endoscopic microsurgery (TEO/TEM) platform was used in 37 patients. Rectal adenocarcinoma was the indication in all except for nine cases of benign diseases. Operative times ranged from 90 to 460 min. TME quality was deemed intact, satisfactory, or complete. Involvement in circumferential resection margins was detected in 16 (11.8 %) patients. The mean lymph node harvest was equal or greater than 12 in all studies. Regarding morbidity, pneumoretroperitoneum, damage to the urethra, and air embolism were reported intraoperatively. Mean hospital stay varied from 4 to 14 days. Postoperative complications occurred in 34 (22.7 %) patients. TaTME with TEM is feasible in selected cases. Oncologic safety parameters seem to be adequate although the evidence relies on small retrospective series conducted by highly trained surgeons. Further studies are expected. PMID:25380741

  20. Evaluating the evidence for evidence-based medicine: are randomized clinical trials less flawed than other forms of peer-reviewed medical research?

    PubMed

    Steen, R Grant; Dager, Stephen R

    2013-09-01

    Evidence-based medicine considers randomized clinical trials (RCTs) to be the strongest form of evidence for clinical decision making. To test the hypothesis that RCTs have fewer methodological flaws than non-RCTs, limitations of 17,591 RCTs and 39,029 non-RCTs were characterized. Panels of experts assembled to write meta-analyses evaluated this literature to determine which articles should be included in 316 meta-analytic reviews. Overall, 38.7% of RCTs evaluated were excluded from review for an identified flaw. Commonly identified flaws in RCTs were as follows: insufficient data provided to evaluate the study (9.6% of 17,591 RCTs); inadequate randomization (9.0%); inadequate blinding (4.9%); and duplicative publication (4.4%). Overall, 20.2% of all published medical research has an identified methodological flaw, with RCTs having as many limitations as non-RCTs. PMID:23695156

  1. 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

  2. In vivo experimental evidence that the major metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency induce oxidative stress in striatum of developing rats: a potential pathophysiological mechanism of striatal damage in this disorder.

    PubMed

    Fernandes, Carolina Gonçalves; da Rosa, Mateus Struecker; Seminotti, Bianca; Pierozan, Paula; Martell, Rafael Wolter; Lagranha, Valeska Lizzi; Busanello, Estela Natacha Brandt; Leipnitz, Guilhian; Wajner, Moacir

    2013-06-01

    3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a genetic disorder biochemically characterized by predominant accumulation of 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA) acids in tissues and biological fluids of affected individuals. Clinically, the patients present neurological symptoms and basal ganglia injury, whose pathomechanisms are partially understood. In the present study, we investigated the ex vivo effects of intrastriatal administration of HMG and MGA on important parameters of oxidative stress in striatum of developing rats. Our results demonstrate that HMG and MGA induce lipid and protein oxidative damage. HMG and MGA also increased 2',7'-dichlorofluorescein oxidation, whereas only HMG elicited nitric oxide production, indicating a role for reactive oxygen (HMG and MGA) and nitrogen (HMG) species in these effects. Regarding the enzymatic antioxidant defenses, both organic acids decreased reduced glutathione concentrations and the activities of superoxide dismutase and glutathione reductase and increased glutathione peroxidase activity. HMG also provoked an increase of catalase activity and a diminution of glucose-6-phosphate dehydrogenase activity. We finally observed that antioxidants fully prevented or attenuated HMG-induced alterations of the oxidative stress parameters, further indicating the participation of reactive species in these effects. We also observed that MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, prevented some of these effects, indicating the involvement of the NMDA receptor in HMG effects. The present data provide solid evidence that oxidative stress is induced in vivo by HMG and MGA in rat striatum and it is presumed that this pathomechanism may explain, at least in part, the cerebral alterations observed in HL deficiency. PMID:23611578

  3. 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

  4. External Collection Devices as an Alternative to the Indwelling Urinary Catheter: Evidence-Based Review and Expert Clinical Panel Deliberations.

    PubMed

    Gray, Mikel; Skinner, Claudia; Kaler, Wendy

    2016-01-01

    Multiple evidence-based guidelines have suggested clinicians consider external collection devices (ECD) as alternatives to indwelling catheters. Nevertheless, there is a dearth of evidence-based resources concerning their use. An expert consensus panel was convened to review the current state of the evidence, indications for ECDs as an alternative to an indwelling urinary catheter, identify knowledge gaps, and areas for future research. This article presents the results of the expert consensus panel meeting and a systematic literature review regarding ECD use in the clinical setting. PMID:26974963

  5. 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

  6. A Clinically Integrated Post-Graduate Training Programme in Evidence-Based Medicine versus ‘No Intervention’ for Improving Disability Evaluations: A Cluster Randomised Clinical Trial

    PubMed Central

    Kok, Rob; Hoving, Jan L.; Smits, Paul B. A.; Ketelaar, Sarah M.; van Dijk, Frank J. H.; Verbeek, Jos H.

    2013-01-01

    Background Although several studies have shown that teaching EBM is effective in improving knowledge, at present, there is no convincing evidence that teaching EBM also changes professional behaviour in practice. Therefore, the primary aim of this study was to evaluate the effectiveness of a clinically integrated post-graduate training programme in EBM on evidence-based disability evaluation. Methods and Findings In a cluster randomised controlled trial, fifty-four case-based learning groups consisting of 132 physicians and 1680 patients were randomly assigned to the intervention or control groups. A clinically integrated, post-graduate, 5-day training programme in evidence-based medicine, consisting of (home) assignments, peer teaching, interactive training in searching databases, lectures and brainstorming sessions was provided to the intervention group. The control group received no training. The primary outcome was evidence-based disability evaluation, as indicated by the frequency in use of evidence of sufficient quality in disability evaluation reports. There are no general EBM behaviour outcome measures available. Therefore, we followed general guidelines for constructing performance indicators and defined an a priori cut-off for determination of sufficient quality as recommended for evaluating EB training. Physicians trained in EBM performed more evidence-based disability evaluations compared to physicians in the control group (difference in absolute proportion 9.7%, 95% CI 3.5 to 15.9). The primary outcome differences between groups remained significant after both cluster-adjusted analysis and additional sensitivity analyses accounting for subjects lost to follow-up. Conclusions A EBM programme successfully improved the use of evidence in a non-hospital based medical specialty. Our findings support the general recommendations to use multiple educational methods to change physician behaviour. In addition, it appeared important that the professional context

  7. Good publication practices in clinical pharmacology: transparency, evidence-based medicine and the 7-D assessment*

    PubMed Central

    Woodcock, Barry G.; Luger, Veronika

    2015-01-01

    Transparency and evidence-based medicine are cornerstones of good publication practices (GPP), and concern publishers, editors, research investigators, and reviewers alike. Methods for implementing these principles within the framework of GPP are described. The main aspects include obtaining a Manuscript Agreement Contract, a Statement on Transparency of Authorship and a Declaration of Conflicts of Interest from the authors. Assessing whether a manuscript meets the requirements of EBM is demonstrated using the “7-D assessment”. The main purpose of this tool is to established that the (1) right Design, (2) right Diagnosis, (3) right Drug molecule, (4) right Dosage, (5) right Data, (6) right Deductions, and (7) right Documentation have been implemented in order to meet the objectives of the investigation. If the findings from any one of these assessments is questionable, the compliance of the research with EBM principles will be weakened and the reviewers and editors will make recommendations to the publisher accordingly. The guidelines described will help to provide a fair and transparent process of scientific publication and foster the freedom of clinical pharmacological research. PMID:26329349

  8. Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation.

    PubMed

    Lin, Hui-Ju; Wei, Chang-Ching; Chang, Ching-Yao; Chen, Ter-Hsin; Hsu, Yu-An; Hsieh, Yi-Ching; Chen, Hsuan-Ju; Wan, Lei

    2016-08-01

    Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%), uveitis (3.7%), or systemic lupus erythematosus (3.5%) compared to those without inflammatory diseases (p<0.001) using data from children (<18years old) in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD), an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA) or the inflammatory stimulators lipopolysaccharide (LPS) or peptidoglycan (PGN). Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia. PMID:27470424

  9. 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. PMID:26195324

  10. CYP17 inhibitors in prostate cancer: latest evidence and clinical potential

    PubMed Central

    Alex, Anitha B.; Pal, Sumanta K.; Agarwal, Neeraj

    2016-01-01

    Since androgen signaling plays a pivotal role in the proliferation and metastasis of prostate cancer, androgen deprivation therapy (ADT) or castration therapy is considered the backbone of treatment for newly diagnosed metastatic prostate cancer. However, almost all men experience disease progression on ADT to a state known as metastatic castration-resistant prostate cancer (mCRPC), which continues to be driven by intratumoral androgen synthesis or androgen receptor signaling. Hence, the extragonadal ablation of androgen synthesis from pregnane precursors holds much promise. An inhibitor of cytochrome P450 17α−hydroxy/17,20-lyase (CYP17) enzymes, abiraterone acetate, has already been approved for men with mCRPC. Newer CYP17 inhibitors continue to be developed which are either more selective or have concomitant inhibitory actions on AR signaling. These include VT-464, orteronel, and galeterone. Herein, we focus on the molecular mechanism of action, efficacy, latest evidence, and clinical potential of CYP17 inhibitors in prostate cancer. PMID:27482286

  11. Future therapeutical strategies dictated by pre-clinical evidence in ALS.

    PubMed

    Fornai, Francesco; Meininger, Vincent; Silani, Vincent

    2011-03-01

    Classic concepts on amyotrophic lateral sclerosis led to define the disease as a selective degeneration of upper and lower motor neurons. At present such selectivity is questioned by novel findings. For instance, the occurrence of frontotemporal dementia is now increasingly recognized in the course of ALS. Again, areas outside the central nervous system are targeted in ALS. In keeping with motor areas other cell types surrounding motor neurons such as glia and interneurons are key in the pathogenesis of ALS. This multiple cell involvement may be due to a prion-like diffusion of specific misfolded proteins which are altered in ALS. This is the case of FUS and TDP-43 which harbor a prion domain prone to pathological misfolding. These misfolded proteins are metabolized by the autophagy, but in ALS there is evidence for a specific deficit of autophagy which impedes the clearance of these proteins. These concepts lead to re-analyze the potential therapeutics of ALS. In fact, mere cell substitution (stem cell) therapy appears insufficient to contrast all the alterations in the various pathways affected by ALS. Although preclinical data speed the application of stem cells in human clinical trials, several hurdles limit their translation into new therapies. Future treatments are expected to consider the need to target both motor neurons and neighboring cells which may contribute to the diffusion and persistence of the disease. On this basis the present manuscript describes which future strategies need to be pursued in order to design optimal therapeutic trial in ALS. PMID:21412723

  12. Vardenafil for the treatment of erectile dysfunction: an overview of the clinical evidence

    PubMed Central

    Morales, Antonio Martín; Mirone, Vincenzo; Dean, John; Costa, Pierre

    2009-01-01

    Many men with erectile dysfunction (ED) also have associated underlying cardiovascular and metabolic conditions, for which they are likely to be taking medication. Therefore, cardiovascular safety and potential drug interactions are two of the major concerns when using PDE-5 inhibitors in these patients. The PDE-5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased duration of erection, high rates of first-dose success and reliable efficacy that can be maintained with continued use. In both clinical trials and real-life observational studies, vardenafil has demonstrated a favorable efficacy and safety profile in men with ED, including those with associated underlying conditions such as diabetes, hypertension and dyslipidemia. Importantly, the concomitant use of medication for these conditions is not associated with any noteworthy changes in the efficacy and safety of vardenafil. The evidence presented in this review supports the use of vardenafil as a first-line treatment for men with ED, including those with underlying conditions. PMID:20054411

  13. Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

    PubMed Central

    Zalpour, Ali; Oo, Thein Hlaing

    2015-01-01

    Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed. PMID:26351456

  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. PMID:11806503

  15. 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. PMID:24025004

  16. Aspergillus Polymerase Chain Reaction: Systematic Review of Evidence for Clinical Use in Comparison With Antigen Testing

    PubMed Central

    White, P. Lewis; Wingard, John R.; Bretagne, Stéphane; Löffler, Jürgen; Patterson, Thomas F.; Slavin, Monica A.; Barnes, Rosemary A.; Pappas, Peter G.; Donnelly, J. Peter

    2015-01-01

    Background. Aspergillus polymerase chain reaction (PCR) was excluded from the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal disease because of limited standardization and validation. The definitions are being revised. Methods. A systematic literature review was performed to identify analytical and clinical information available on inclusion of galactomannan enzyme immunoassay (GM-EIA) (2002) and β-d-glucan (2008), providing a minimal threshold when considering PCR. Categorical parameters and statistical performance were compared. Results. When incorporated, GM-EIA and β-d-glucan sensitivities and specificities for diagnosing invasive aspergillosis were 81.6% and 91.6%, and 76.9% and 89.4%, respectively. Aspergillus PCR has similar sensitivity and specificity (76.8%–88.0% and 75.0%–94.5%, respectively) and comparable utility. Methodological recommendations and commercial PCR assays assist standardization. Although all tests have limitations, currently, PCR is the only test with independent quality control. Conclusions. We propose that there is sufficient evidence that is at least equivalent to that used to include GM-EIA and β-d-glucan testing, and that PCR is now mature enough for inclusion in the EORTC/MSG definitions. PMID:26113653

  17. Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

    PubMed

    Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

    2015-12-01

    Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. PMID:26499757

  18. 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.

  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. PMID:25450429

  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. 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

  2. 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

  3. Acceleration of large active earthflows triggered by massive snow accumulation events: evidences from monitoring the Corvara landslide in early 2014 (Dolomites, Italy)

    NASA Astrophysics Data System (ADS)

    Corsini, Alessandro; Mulas, Marco; Marcato, Gianluca; Chinellato, Giulia; Mair, Volkmar

    2015-04-01

    In the Dolomites of Italy, snowfall during winter 2013/2014 was exceptionally abundant. Major snowfall events occurred from late December 2013 to mid-March 2014. Snow accumulation in Badia Valley peaked in early February: from 2 to 4 meters with a positive gradient respect to altimetry and accordingly to wind accumulation zones. Below 2000 m asl, due to the mild temperatures recorded before the onset of snowfall, the relatively dry snow cover was mostly deposited on top of unfrozen soils. The Corvara landslide is a large active earthflow located close to Corvara in Badia, at an elevation from 2000 to 1600 m. It's displacement rate before, during and after the exceptional snowfall period was monitored at high temporal frequency. Surface displacement was measured bi-weekly by differential GPS in several benchmarks in the source, track and accumulation zone. Deep displacement was monitored semi-continuously by two in-place inclinometers at 48 m depth in the accumulation zone, across the main deep-seated sliding surface. Results show an acceleration of movements, both at surface and at depth, soon after the massive snow accumulation event of 31st January to 2nd February 2014, which suddenly increased snow thickness from 1 to more than 2 metres. Short time lags between the onset of the acceleration of movements in the source, the track and the accumulation zones were also recorded. The landslide then maintained a relatively constant velocity during the high snow cover period extended to earlyApril and underwent a progressive deceleration during the snowmelt period that lasted until mid-June. The fact that the acceleration of the Corvara earthflow was triggered by a massive and rapid snow accumulation event, provides a quite different perspective from the generally adopted one that considers the destabilizing effect of snow only in relation to the increase of groundwater level during rapid snowmelt. A full explanation of the processes associated to the dynamics observed

  4. Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study

    PubMed Central

    Phi, Linda; Ajaj, Reem; Ramchandani, Manisha H; Brant, Xenia MC; Oluwadara, Oluwadayo; Polinovsky, Olga; Moradi, David; Barkhordarian, Andre; Sriphanlop, Pathu; Ong, Margaret; Giroux, Amy; Lee, Justin; Siddiqui, Muniza; Ghodousi, Nora; Chiappelli, Francesco

    2012-01-01

    Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) Working Group developed an instrument called the GRADE system in order to grade the quality of the evidence in studies and to evaluate the strength of recommendation of the intervention that is proposed in the published article. The GRADE looks at four factors to determine the quality of the evidence: study design, study quality, consistency, and directness. After combining the four components and assessing the grade of the evidence, the strength of recommendation of the intervention is established. The GRADE, however, only makes a qualitative assessment of the evidence and does not generate quantifiable data. In this study, we have quantified both the grading of the quality of evidence and also the strength of recommendation of the original GRADE, hence expanding the GRADE. This expansion of the GRADE (Ex-GRADE) permits the creation of a new instrument that can produce tangible data and possibly bridge the gap between evidence-based research and evidence-based clinical practice. PMID:22303416

  5. 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…

  6. How are autism and schizotypy related? Evidence from a non-clinical population.

    PubMed

    Dinsdale, Natalie L; Hurd, Peter L; Wakabayashi, Akio; Elliot, Mick; Crespi, Bernard J

    2013-01-01

    Both autism spectrum conditions (ASCs) and schizophrenia spectrum conditions (SSCs) involve altered or impaired social and communicative functioning, but whether these shared features indicate overlapping or different etiological factors is unknown. We outline three hypotheses (overlapping, independent, and diametric) for the possible relationship between ASCs and SSCs, and compare their predictions for the expected relationships between autistic and schizotypal phenotypes using the Autism Spectrum Quotient and the Schizotypal Personality Questionnaire-Brief Revised from a large non-clinical sample of undergraduate students. Consistent with previous research, autistic features were positively associated with several schizotypal features, with the most overlap occurring between interpersonal schizotypy and autistic social and communication phenotypes. The first component of a principal components analysis (PCA) of subscale scores reflected these positive correlations, and suggested the presence of an axis (PC1) representing general social interest and aptitude. By contrast, the second principal component (PC2) exhibited a pattern of positive and negative loadings indicative of an axis from autism to positive schizotypy, such that positive schizotypal features loaded in the opposite direction to core autistic features. These overall PCA patterns were replicated in a second data set from a Japanese population. To evaluate the validity of our interpretation of the PCA results, we measured handedness and mental rotation ability, as these are established correlates of SSCs and ASCs, respectively. PC2 scores were significantly associated with hand preference, such that increasingly 'schizotypal' scores predicted reduced strength of handedness, which is consistent with previous research. PC1 scores were positively related to performance on the mental rotation task, suggesting trade-offs between social skills and visual-spatial ability. These results provide novel evidence

  7. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

    PubMed

    Iwakiri, Katsuhiko; Kinoshita, Yoshikazu; Habu, Yasuki; Oshima, Tadayuki; Manabe, Noriaki; Fujiwara, Yasuhiro; Nagahara, Akihito; Kawamura, Osamu; Iwakiri, Ryuichi; Ozawa, Soji; Ashida, Kiyoshi; Ohara, Shuichi; Kashiwagi, Hideyuki; Adachi, Kyoichi; Higuchi, Kazuhide; Miwa, Hiroto; Fujimoto, Kazuma; Kusano, Motoyasu; Hoshihara, Yoshio; Kawano, Tatsuyuki; Haruma, Ken; Hongo, Michio; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-08-01

    As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended. PMID:27325300

  8. Binocular Depth Perception in Individuals at Clinical High Risk for Psychosis: no evidence of dysfunction

    PubMed Central

    Barbato, Mariapaola; Addington, Jean

    2014-01-01

    Objective In the last decade the interest in the role of the visual system in schizophrenia has grown, with evidence pointing to dysfunction in bottom-up visual processing that leads to early visual processing deficits. A fundamental component of visual perception is binocular depth perception (BDP), i.e. depth perception derived by the difference between the images impressed upon the left and right retina. Two studies reported impaired BDP in schizophrenia and suggested a possible developmental deficit of brain structures involved in early visual processing. The aim of this study was to examine BDP in a young population at clinical high risk (CHR) of developing psychosis to determine if this dysfunction is present in this potentially pre-psychotic period. Methods Forty-two CHR participants and 44 healthy controls were assessed using a computerized test of depth perception; a subsample completed a test of stereopsis. The computerized test was comprised of two trial blocks, with four conditions at increasing level of difficulty, where participants were asked to discriminate the relative depth of two stimuli simultaneously presented on the screen. Results BDP was not impaired in the CHR group, whose performance was similar to that of the control group on both measures. For the CHR group performance in both tests was not correlated to positive symptoms. Conclusions These results indicate that BDP is preserved in individuals at CHR for psychosis and impaired BDP should not be considered a vulnerability marker for schizophrenia. Nevertheless future studies should verify BDP's potential power in predicting schizophrenia. PMID:24188117

  9. Third-generation neuroimaging in early schizophrenia: translating research evidence into clinical utility.

    PubMed

    Borgwardt, Stefan; Fusar-Poli, Paolo

    2012-04-01

    Psychiatric imaging needs to move away from simple investigations of the neurobiology underlying the early phases of schizophrenia to translate imaging findings in the clinical field, targeting clinical outcomes including transition, remission and response to preventive interventions. PMID:22474231

  10. Evidence-based use of electronic clinical tracking systems in advanced practice registered nurse education: an integrative review.

    PubMed

    Branstetter, M Laurie; Smith, Lynette S; Brooks, Andrea F

    2014-07-01

    Over the past decade, the federal government has mandated healthcare providers to incorporate electronic health records into practice by 2015. This technological update in healthcare documentation has generated a need for advanced practice RN programs to incorporate information technology into education. The National Organization of Nurse Practitioner Faculties created core competencies to guide program standards for advanced practice RN education. One core competency is Technology and Information Literacy. Educational programs are moving toward the utilization of electronic clinical tracking systems to capture students' clinical encounter data. The purpose of this integrative review was to evaluate current research on advanced practice RN students' documentation of clinical encounters utilizing electronic clinical tracking systems to meet advanced practice RN curriculum outcome goals in information technology as defined by the National Organization of Nurse Practitioner Faculties. The state of the science depicts student' and faculty attitudes, preferences, opinions, and data collections of students' clinical encounters. Although electronic clinical tracking systems were utilized to track students' clinical encounters, these systems have not been evaluated for meeting information technology core competency standards. Educational programs are utilizing electronic clinical tracking systems with limited evidence-based literature evaluating the ability of these systems to meet the core competencies in advanced practice RN programs. PMID:24814999

  11. Evidence-based cariology in clinical and public health practice as part of the European Core Curriculum in Cariology.

    PubMed

    Splieth, Ch H; Innes, N; Söhnel, A

    2011-11-01

    This paper is part of a series of papers contributing towards a European Core Curriculum in Cariology for undergraduate dental students. The European Core Curriculum in Cariology is the outcome of a process starting in 2006 and culminating in a joint workshop of the European Organization for Caries Research together with the Association for Dental Education in Europe, which was held in Berlin from 27 to 30 June 2010. The scope of this paper is to present the evidence-based cariology in clinical and public health section of the European Core Curriculum in Cariology. This section was developed on the basis of international consensus on the current and future educational needs in the fields of cariology and disorders of dental hard tissues. The paper will deal with the core skills of evidence-based dental practice within the undergraduate curriculum underpinning the dual facets of clinical cariology (relating particularly to individuals) and public health cariology (relating particularly to groups/societies). Core competencies in evidence-based dentistry, which are generic to the undergraduate curriculum as a whole and not only cariology, are integral to lifelong learning skills within dentistry. As the clinical cariology competencies in assessment and management of caries for the individual patient are dealt with within other sections of the European Core Curriculum in Cariology, only a few relevant examples will be presented here, but for Public Health Cariology, the competencies will be explored within this document and their relationship to the principles of evidence-based dentistry discussed. PMID:22023546

  12. Comparison of residents’ approaches to clinical decisions before and after the implementation of Evidence Based Medicine course

    PubMed Central

    KARIMIAN, ZAHRA; KOJURI, JAVAD; SAGHEB, MOHAMMAD MAHDI; MAHBOUDI, ALI; SABER, MAHBOOBEH; AMINI, MITRA; DEHGHANI, MOHAMMAD REZA

    2014-01-01

    Introduction: It has been found that the decision-making process in medicine is affected, to a large extent, by one’s experience, individual mentality, previous models, and common habitual approaches, in addition to scientific principles. Evidence-based medicine is an approach attempting to reinforce scientific, systematic and critical thinking in physicians and provide the ground for optimal decision making. In this connection, the purpose of the present study is to find out to what extent the education of evidence based medicine affects clinical decision making. Methods: The present quasi-experimental study was carried out on 110 clinical residents, who started their education in September, 2012 and finally 62 residents filled out the questionnaires. The instrument used was a researcher-made questionnaire containing items on four decision-making approaches. The questionnaire was used both as a pre-test and a post-test to assess the residents’ viewpoints on decision making approaches. The validity of the questionnaire was determined using medical education and clinical professionals’ viewpoints, and the reliability was calculated through Chronbach alpha; it was found to be 0.93. The results were analyzed by paired t-test using SPSS, version 14. Results: The results demonstrated that evidence-based medicine workshop significantly affected the residents’ decision-making approaches (p<0.001). The pre-test showed that principles-based, reference-based and routine model-based approaches were more preferred before the program (p<0.001). However, after the implementation of the program, the dominant approaches used by the residents in their decision making were evidence-based ones.  Conclusion: To develop the evidence-based approach, it is necessary for educational programs to continue steadily and goal-orientedly. In addition, the equipment infrastructure such as the Internet, access to data bases, scientific data, and clinical guides should develop more in the

  13. Frailty: Scaling from Cellular Deficit Accumulation?

    PubMed

    Rockwood, Kenneth; Mitnitski, Arnold; Howlett, Susan E

    2015-01-01

    Cells age in association with deficit accumulation via mechanisms that are far from fully defined. Even so, how deficits might scale up from the subcellular level to give rise to clinically evident age-related changes can be investigated. This 'scaling problem' can be viewed either as a series of little-related events that reflect discrete processes--such as the development of particular diseases--or as a stochastic process with orderly progression at the systems level, regardless of which diseases are present. Some recent evidence favors the latter hypothesis, but determining the best approach to study how deficits scale remains a key goal for understanding aging. In consequence, approaching the problem of frailty as one of the scaling of subcellular deficits has implications for understanding aging. Considering the cumulative effects of many small deficits appears to allow for the observation of important aspects of the behavior of systems that are close to failure. Mathematical modeling offers useful possibilities in clarifying the extent to which different clinical scales measure different phenomena. Even so, to be useful, mathematical modelling must be clinically coherent in addition to mathematically sound. In this regard, queuing appears to offer some potential for investigating how deficits originate and accumulate. PMID:26301975

  14. Ground penetrating radar (GPR) evidence for variations in free phase carbon gas accumulation as a function of peatland landforms: a comparison between near-crest bogs and mid-slope lawns

    NASA Astrophysics Data System (ADS)

    Parsekian, A.; Slater, L.; Comas, X.; Nolan, J.; Glaser, P.

    2009-05-01

    Northern peatlands serve as atmospheric sources of biogenic free-phase gas (FPG) produced under anaerobic conditions below the water table (mostly methane and carbon dioxide). Recent evidence suggest that FPG accumulates in the subsurface under confining layers and is released during sudden ebullition events, often triggered by sudden drops in atmospheric pressure. Accurate quantification of the impact of FPG releases on the global carbon budget is needed given recent observations of increasing atmospheric methane concentrations. One important step towards understanding the dynamics of FPG in peatlands is to investigate whether certain peatland landforms (i.e. areas with significantly different vegetation patterns) may be more conducive to FPG accumulation and/or release. Additionally, it is important to determine the vertical distribution of FPG within the peat soil and the potential role of peat stratigraphy on gas accumulation and release. In this study, we used common mid-point (CMP) velocity surveys to predict vertical profiles of FPG accumulations by comparing two different peatland landforms: historically forested near-crest bogs and non- forested mid-slope lawns in the Glacial Lake Agassiz Peatland of Minnesota, USA. We show that there is a statistically significant difference in electromagnetic (EM) wave velocities calculated over gas-rich intervals in the peat strata compared to gas-poor intervals. Common-offset radar profiles identified laterally continuous woody confining layers responsible for FPG accumulation. Chaotic GPR facies containing diffraction hyperbolae at the forested near-crest sites are interpreted as deformation of the peat matrix due to FPG accumulation and/or peat fabric disturbance during FPG release events. In contrast, non-forested mid-slope lawn sites, are characterized by planar GPR facies with no evidence of peat fabric disturbance and small relative changes in interpreted EM velocity distribution along the peat column. Using the

  15. Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) in the Asia Pacific region (Round Table Forum).

    PubMed

    Su, Tin Tin; Bulgiba, Awang M; Sampatanukul, Pichet; Sastroasmoro, Sudigdo; Chang, Peter; Tharyan, Prathap; Lin, Vivian; Wong, Yut Lin

    2013-01-01

    Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) have become increasingly important in an era of rising costs, patient safety concerns and evidence-based health care. CE and EBM research in the Asia Pacific region have grown significantly. However, there are three main challenges such as linking evidence to practice and policy; developing a strong collaborative network; and a need for resources and technical expertise to produce evidence. The Cochrane Collaboration is a possible solution to resolve above challenges identified, particularly the challenge of transforming evidence to practice. In addition, training can be carried out to enhance technical expertise in the region and there is also the promising potential that collaborations could extend beyond systematic reviews. To improve the adoption of evidence-based health policy, selection of the best evidence for the right audience and focusing on the relevant issues through appropriate methodology are essential. Information on effectiveness and cost effectiveness needs to be highlighted for policy makers. The way forward to strengthen research and capacity building is to establish the Asia Pacific Consortium for CE and EBM. The consortium would help to create mutually rewarding scientific research and collaborations that will augur well for advances in CE and EBM. PMID:23624253

  16. 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.

  17. Perioperative Nursing Leaders Implement Clinical Practice Guidelines Using the Iowa Model of Evidence-Based Practice.

    PubMed

    White, Shawna; Spruce, Lisa

    2015-07-01

    Many health care organizations, nursing leaders, and individual clinicians are not providing care consistently based on evidence and many are not aware of the evidence that is available. Preventable complications have an adverse effect on hospital reimbursement and the burden is placed on hospital personnel and nursing leaders to use current evidence to improve care and prevent complications, such as surgical site infections. Using AORN resources, leadership involvement and ownership, and implementing a theoretical model will contribute to implementing daily evidence-based practice and help to decrease the chasm between research and practice. PMID:26119609

  18. β Blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study

    PubMed Central

    Spargias, K; Hall, A; Greenwood, D; Ball, S

    1999-01-01

    Objectives—To examine clinical outcomes associated with optional β blockade in a population of patients with evidence of heart failure after myocardial infarction.
Design and patients—Data from the acute infarction ramipril efficacy (AIRE) study were analysed retrospectively. At baseline 22.3% of the patients were receiving a β blocker. To minimise confounding, β blocker and diuretic treatments, presence of clinical signs of heart failure, left ventricular ejection fraction, and 16 other baseline clinical variables were simultaneously entered in a multivariate Cox regression model. In addition, the same analysis was repeated separately within a high and a low risk group of patients, as defined according to the need for diuretic treatment.
Results—β Blocker treatment was an independent predictor of reduced risk of total mortality (hazard ratio 0.66, 95% confidence interval (CI) 0.48 to 0.90) and progression to severe heart failure (0.58, 95% CI 0.40 to 0.83) for the entire study population. There were similar findings in high risk patients requiring diuretics (0.59, 95% CI 0.40 to 0.86; and 0.58, 95% CI 0.38 to 0.89).
Conclusions—β Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure.

 Keywords: myocardial infarction;  heart failure;  left ventricular dysfunction;  β blockers PMID:10220541

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

    PubMed

    Reginster, Jean-Yves; Beaudart, Charlotte; Neuprez, Audrey; Bruyère, Olivier

    2013-10-01

    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 ranelate

  20. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models.

    PubMed

    White, Carl W; Martin, James G

    2010-07-01

    Humans can come into contact with chlorine gas during short-term, high-level exposures due to traffic or rail accidents, spills, or other disasters. By contrast, workplace and public (swimming pools, etc.) exposures are more frequently long-term, low-level exposures, occasionally punctuated by unintentional transient increases. Acute exposures can result in symptoms of acute airway obstruction including wheezing, cough, chest tightness, and/or dyspnea. These findings are fairly nonspecific, and might be present after exposures to a number of inhaled chemical irritants. Clinical signs, including hypoxemia, wheezes, rales, and/or abnormal chest radiographs may be present. More severely affected individuals may suffer acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Up to 1% of exposed individuals die. Humidified oxygen and inhaled beta-adrenergic agents are appropriate therapies for victims with respiratory symptoms while assessments are underway. Inhaled bicarbonate and systemic or inhaled glucocorticoids also have been reported anecdotally to be beneficial. Chronic sequelae may include increased airways reactivity, which tends to diminish over time. Airways hyperreactivity may be more of a problem among those survivors that are older, have smoked, and/or have pre-existing chronic lung disease. Individuals suffering from irritant-induced asthma (IIA) due to workplace exposures to chlorine also tend to have similar characteristics, such as airways hyperresponsiveness to methacholine, and to be older and to have smoked. Other workplace studies, however, have indicated that workers exposed to chlorine dioxide/sulfur dioxide have tended to have increased risk for chronic bronchitis and/or recurrent wheezing attacks (one or more episodes) but not asthma, while those exposed to ozone have a greater incidence of asthma. Specific biomarkers for acute and chronic exposures to chlorine gas are currently lacking. Animal models for chlorine gas

  1. Neuroimaging and treatment evidence for clinical staging in psychotic disorders: from the at-risk mental state to chronic schizophrenia.

    PubMed

    Wood, Stephen J; Yung, Alison R; McGorry, Patrick D; Pantelis, Christos

    2011-10-01

    A new approach to understanding severe mental disorders such as schizophrenia is to adopt a clinical staging model. Such a model defines the extent of the illness such that earlier and milder phenomena are distinguished from later, more impairing features. Specifically, a clinical staging model makes three key predictions. First, pathologic measures should be more abnormal in more severe stages. Second, patients who progress between the stages should show change in these same pathologic measures. Finally, treatment should be more effective in the earlier stages, as well as more benign. In this article, we review the evidence for these three predictions from studies of psychotic disorders, with a focus on neuroimaging data. For all three, the balance of evidence supports the predictions of the staging model. However, there are a number of alternative explanations for these findings, including the effects of medication and symptom heterogeneity. PMID:21762875

  2. 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 PMID:27505406

  3. 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

  4. Clarifying Evidence-Based Medicine in Educational and Therapeutic Experiences of Clinical Faculty Members: A Qualitative Study in Iran

    PubMed Central

    Safari, Yahya

    2015-01-01

    Introduction: Although evidence-based medicine has been a significant part of recent research efforts to reform the health care system, it requires an assessment of real life community and patient. The present study strives to clarify the concept of evidence-based medicine in educational and therapeutic experiences of clinical faculty members of Kermanshah University of Medical Sciences (2014). Materials and Methods: It was a qualitative study of phenomenology. The population consists of 12 clinical faculty members of Kermanshah University Medical Sciences. Sampling was carried out using a purposeful method. Sample volume was determined using adequacy of samples’ law. Data gathering occurred through semi-structured interviews. Collaizzi pattern was employed for data interpretation concurrent with data gathering. Results: interpreting the data, three main themes were extracted. They include: 1. Unawareness and disuse (unaware of the concept, disuse, referral to colleagues, experiment prescription) 2. Conscious or unconscious use (using journals and scientific websites, aware of the process). 3. Beliefs (belief or disbelief in necessity). Conclusion: It sounds essential to change the behavior of clinical faculty members from passive to active with respect to employing evidence-based medicine as well as to alter negative attitudes into positive ones. In so doing, systematic training program aiming at behavior changing is necessary. Also, providing dissent facilities and infrastructures and removing barriers to the use of EBM can be effective. PMID:26153205

  5. 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…

  6. 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. PMID:25955430

  7. 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. PMID:20437040

  8. Evidence of various mechanisms of Cd sequestration in the hyperaccumulator Arabidopsis halleri, the non-accumulator Arabidopsis lyrata, and their progenies by combined synchrotron-based techniques.

    PubMed

    Isaure, Marie-Pierre; Huguet, Stéphanie; Meyer, Claire-Lise; Castillo-Michel, Hiram; Testemale, Denis; Vantelon, Delphine; Saumitou-Laprade, Pierre; Verbruggen, Nathalie; Sarret, Géraldine

    2015-06-01

    Arabidopsis halleri is a model plant for Zn and Cd hyperaccumulation. The objective of this study was to determine the relationship between the chemical forms of Cd, its distribution in leaves, and Cd accumulation and tolerance. An interspecific cross was carried out between A. halleri and the non-tolerant and non-hyperaccumulating relative A. lyrata providing progenies segregating for Cd tolerance and accumulation. Cd speciation and distribution were investigated using X-ray absorption spectroscopy and microfocused X-ray fluorescence. In A. lyrata and non-tolerant progenies, Cd was coordinated by S atoms only or with a small contribution of O groups. Interestingly, the proportion of O ligands increased in A. halleri and tolerant progenies, and they were predominant in most of them, while S ligands were still present. Therefore, the binding of Cd with O ligands was associated with Cd tolerance. In A. halleri, Cd was mainly located in the xylem, phloem, and mesophyll tissue, suggesting a reallocation process for Cd within the plant. The distribution of the metal at the cell level was further discussed. In A. lyrata, the vascular bundles were also Cd enriched, but the epidermis was richer in Cd as compared with the mesophyll. Cd was identified in trichomes of both species. This work demonstrated that both Cd speciation and localization were related to the tolerance character of the plant. PMID:25873676

  9. Essential content of evidence-based clinical practice guidelines for bladder cancer: The Japanese Urological Association 2015 update.

    PubMed

    Kubota, Yoshinobu; Nakaigawa, Noboru

    2016-08-01

    The Japanese Urological Association revised the clinical practice guidelines for bladder cancer in April 2015. This was the first update carried out in the 6 years since the development of the initial clinical practice guidelines for bladder cancer in 2009. The descriptive content was revised, and additions were made with a focus on new-found evidence and advances in the latest medical practices, and on the basis of the increasingly aging population observed in the underlying social context in Japan. An algorithm for the treatment of bladder cancer has been presented as a new trial. In the present article, we will introduce the essential contents and clinical questions that address the present revisions. PMID:27374472

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

    PubMed

    Cynk, Mark

    2014-04-01

    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. 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

  12. Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence.

    PubMed

    Srinivas, Nuggehally R

    2013-12-01

    The area of fruit juice-drug interaction has received wide attention with numerous scientific and clinical investigations performed and reported for scores of drugs metabolized by CYP3A4/CYP2C9. While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance. This review focuses on establishing any relevance for clinical drug-drug interaction potential with pomegranate juice, which has been shown to produce therapeutic benefits over a wide range of disease areas. The review collates and evaluates relevant published in vitro, preclinical and clinical evidence of the potential of pomegranate juice to be a perpetrator in drug-drug interactions mediated by CYP3A4 and CYP2C9. In vitro and animal pharmacokinetic data support the possibility of CYP3A4/CYP2C9 inhibition by pomegranate juice; however, the human relevance for drug-drug interaction was not established based on the limited case studies. PMID:23673492

  13. Evidence of clinically significant change: the therapeutic alliance and the possibilities of outcomes-informed care.

    PubMed

    Manning, Walter H

    2010-11-01

    This article addresses the issue of clinically significant (or meaningful) change resulting from treatment for stuttering. Research in both medical and behavioral fields indicates that clients often have their own unique perspective of meaningful clinical change and that this perspective is often different from that of the professional administering the treatment. Among the variables that the client brings to the treatment session are their progression through stages of therapeutic change and the ways in which they believe they are capable of coping with their problem. Research has shown that how an individual interprets the meaning his or her therapeutic experience is central to clinically significant change. Procedures for obtaining feedback from clients concerning clinically significant change and the quality of the therapeutic alliance are described. PMID:21080293

  14. Consensus evidence-based guidelines for use of insulin pump therapy in the management of diabetes as per Indian clinical practice.

    PubMed

    Kesavadev, Jothydev; Jain, Sunil M; Muruganathan, A; Das, Ashok Kumar

    2014-07-01

    The use of insulin pump in diabetes is likely to increase with recent advances in technology. Although the evidence for the superiority of pumps over multiple daily injections (MDI) is inconsistent, data from accumulating uncontrolled studies indicate greater reductions in glycated haemoglobin in patients switching to continuous subcutaneous insulin infusion (CSII) from MDI therapy. Due to the variability in insulin requirements and sensitivity to CSII pumps, hyperglycaemia in these patients is managed by endocrinologists using individualised therapy. A panel of experts reviewed the existing guidelines and framed recommendations specific to the clinical practice in Indian conditions for use of CSII pumps in the management of hyperglycaemia. Selection of right patient with basic education, motivation and learning skills are essential for successful implementation of CSII therapy with sophisticated programmes. Rapid acting insulin analogues with better pharmacokinetic and pharmacodynamic profile, physical and chemical stability and compatibility with most commercially available insulin pumps are preferred over regular insulin to achieve safe and stable glycaemic control. Further, educating pump users on proper use of CSII pumps, insulin dose adjustments, and handling of accessories are recommended in the current consensus guidelines. Practice of self-monitoring of blood glucose and glycated haemoglobin levels are essential to adjust insulin dosage for the management of diabetes. Use of CSII pumps in special patient populations should be carefully assessed and initiated by endocrinologist. The proposed guidelines can form a basis for use of CSII pumps in the management of hyperglycaemia in the Indian scenario. PMID:25668935

  15. 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

  16. 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

  17. Clinical practice guidelines for gastric cancer in Korea: an evidence-based approach.

    PubMed

    Lee, Jun Haeng; Kim, Jae G; Jung, Hye-Kyung; Kim, Jung Hoon; Jeong, Woo Kyoung; Jeon, Tae Joo; Kim, Joon Mee; Kim, Young Il; Ryu, Keun Won; Kong, Seong-Ho; Kim, Hyoung-Il; Jung, Hwoon-Yong; Kim, Yong Sik; Zang, Dae Young; Cho, Jae Yong; Park, Joon Oh; Lim, Do Hoon; Jung, Eun Sun; Ahn, Hyeong Sik; Kim, Hyun Jung

    2014-06-01

    Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase. PMID:25061536

  18. 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

  19. Electronic health record: integrating evidence-based information at the point of clinical decision making.

    PubMed

    Fowler, Susan A; Yaeger, Lauren H; Yu, Feliciano; Doerhoff, Dwight; Schoening, Paul; Kelly, Betsy

    2014-01-01

    The authors created two tools to achieve the goals of providing physicians with a way to review alternative diagnoses and improving access to relevant evidence-based library resources without disrupting established workflows. The “diagnostic decision support tool” lifted terms from standard, coded fields in the electronic health record and sent them to Isabel, which produced a list of possible diagnoses. The physicians chose their diagnoses and were presented with the “knowledge page,” a collection of evidence-based library resources. Each resource was automatically populated with search results based on the chosen diagnosis. Physicians responded positively to the “knowledge page.” PMID:24415920

  20. Refining the Journal Club Presentations of Postgraduate Students in Seven Clinical Departments for Better Evidence-based Practice

    PubMed Central

    Herur, A; Kolagi, S; Ramadurg, U; Hiremath, CS; Hadimani, CP; Goudar, SS

    2016-01-01

    Background: A gap between best practice and actual clinical care exists and this can be overcome by evidence-based practice (EBP), which is essential to improve the clinical decision making. A strategy to reduce deficits in care provision is to train the postgraduate students in the practice of EBP in the journal clubs as evidence from medical colleges in India reveals that current format of journal club presentations is unsatisfactory. Aim: The aim of the present study was to refine the journal club presentations of postgraduate students of clinical departments and to study the effectiveness of EBP training in them for better EBP. Subjects and Methods: This study was conducted in S. Nijalingappa Medical College, Bagalkot, Karnataka, India, and it was a pre- and post-trial. This study was a pre- and post-trial done during the journal club presentations of postgraduate students from clinical departments. Postgraduate students' understanding of concepts about EBP was assessed using Fresno test questionnaire in traditional journal club presentation. A hands-on session incorporating steps of EBP was imparted to them. Soon after the session, each student was assessed. In the next journal club presentation, 1 week later, the students were assessed again with the same questionnaire by the same faculty. Scores of the postgraduate students, before and after intervention (immediate and 1 week later), were compared. Data were analyzed by paired t-test using SPSS. Results: An increase in mean posttest scores was seen immediately and also 1 week later as compared to the pretest scores. The scores also increased significantly, when each step of EBP was considered. Conclusions: Incorporating teaching of EBP in journal club presentations improved the competencies of postgraduate students in clinical decision making. PMID:27398252

  1. 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

  2. Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

    PubMed Central

    Renoir, Thibault

    2013-01-01

    Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition. PMID:23596418

  3. 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…

  4. 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…

  5. British Fertility Society Policy and Practice Committee: adjuvants in IVF: evidence for good clinical practice.

    PubMed

    Nardo, Luciano G; El-Toukhy, Tarek; Stewart, Jane; Balen, Adam H; Potdar, Neelam

    2015-03-01

    Optimisation of the environment favourable for satisfactory ovarian response to stimulation and successful embryo implantation remains at the core of assisted conception programmes. The evidence base for the routine use of different adjuvants, alone or in combination, for women undergoing their first in vitro fertilisation (IVF) treatment cycle and for those with poor prognosis is inadequate. The aim of this document is to update the last review of the available literature carried out by the British Fertility Society Policy and Practice Committee (BFS P&P) published in 2009 and to provide fertility professionals with evidence-based guidance and recommendations regarding the use of immunotherapy, vasodilators, uterine relaxants, aspirin, heparin, growth hormone, dehydroepiandrosterone, oestrogen and metformin as adjuvants in IVF. Unfortunately despite the lapse of 5 years since the last publication, there is still a lack of robust evidence for most of the adjuvants searched and large well-designed randomised controlled trials are still needed. One possible exception is metformin, which seems to have a positive effect in women with polycystic ovary syndrome undergoing IVF. Patients who are given other adjuvants on an empirical basis should always be informed of the lack of evidence and the potential side effects. PMID:25531921

  6. Engaging a Nursing Workforce in Evidence-Based Practice: Introduction of a Nursing Clinical Effectiveness Committee.

    PubMed

    McKeever, Stephen; Twomey, Bernadette; Hawley, Meaghan; Lima, Sally; Kinney, Sharon; Newall, Fiona

    2016-02-01

    This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787. PMID:26606269

  7. 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.

  8. 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

  9. 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…

  10. 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…

  11. 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. PMID:27173657

  12. 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…

  13. 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…

  14. 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…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

    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…

  16. 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…

  17. 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. PMID:26394796

  18. 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…

  19. 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

  20. [Economic aspects of inpatient treatment for decompensated liver cirrhosis: a prospective study employing an evidence-based clinical pathway].

    PubMed

    Hahn, N; Bobrowski, C; Weber, E; Simon, P; Kraft, M; Aghdassi, A; Raetzell, M; Wilke, M; Lerch, M M; Mayerle, J

    2013-03-01

    The introduction of the G-DRG reimbursement system has greatly increased the pressure to provide cost effective treatment in German hospitals. Reimbursement based on diagnosis-related groups, which requires stratification of costs incurred is still not sufficiently discriminating the disease severity and severity in relation to the intensive costs in gastroenterology. In a combined retrospective and prospective study at a tertial referral centre we investigated whether this also applies for decompensated liver cirrhosis. In 2006, 64 retrospective cases (age 57 ± 12.9; ♂ 69.2 %, ♀ 29.8 %) with decompensated liver cirrhosis (ICD code K76.4) were evaluated for their length of hospitalisation, reimbursement as well as Child and MELD scores. In 2008, 74 cases with decompensated liver cirrhosis were treated in a prospective study according to a standardised and evidence-based clinical pathway (age 57 ± 12.2; 73 % ♂, ♀ 27 %). Besides a trend in the reduction of length of hospital stay (retrospective: 13.6 ± 8.6, prospective 13.0 ± 7.2, p = 0.85) overall revenues from patients treated according to a evidence-based clinical pathway were lower than the calculated costs from the InEK matrix. Costs of medication as a percentage of reimbursement amount increased with increasing severity. In both years we could demonstrate an inverse correlation between daily reimbursement and disease severity which precluded cost coverage. For the cost-covering hospital treatment of patients with decompensated liver cirrhosis an adjustment of the DRG based on clinical severity scores such as Child-Pugh or MELD is warranted, if evidence-based treatment standards are to be kept. PMID:23299901

  1. Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment

    PubMed Central

    Slattery, David A.; Neumann, Inga D.

    2010-01-01

    Affective disorders represent the most common psychiatric diseases, with substantial co-morbidity existing between major depressive disorders (MDD) and anxiety disorders. The lack of truly novel acting compounds has led to non-monoaminergic based research and hypotheses in recent years. The large number of brain neuropeptides, characterized by discrete synthesis sites and multiple receptors, represent likely research candidates for novel therapeutic targets. The present review summarises the available preclinical and human evidence regarding the neuropeptide, oxytocin, and its implications in the aetiology and treatment of MDD. While the evidence is not conclusive at present additional studies are warranted to determine whether OXT may be of therapeutic benefit in subsets of MDD patients such as those with comorbid anxiety symptoms and low levels of social attachment.

  2. 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. PMID:18414362

  3. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.

    PubMed

    Sarris, Jerome; McIntyre, Erica; Camfield, David A

    2013-04-01

    Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations of anxiolytic activity. A search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) for English language papers using the search terms 'anxiety' OR 'anxiety disorder' OR 'generalized anxiety disorder' OR 'social phobia' OR 'post-traumatic stress disorder' OR 'panic disorder' OR 'agoraphobia' OR 'obsessive compulsive disorder' in combination with the search terms 'Herb*' OR 'Medicinal Plants' OR 'Botanical Medicine' OR 'Chinese herb*', in addition to individual herbal medicines. This search of the literature revealed 1,525 papers, of which 53 plants were included in the review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed here in part two), with the other 32 having solely preclinical evidence (reviewed in part one). Support for efficacy was found for chronic use (i.e. greater than one day) of the following herbs in treating a range of anxiety disorders in human clinical trials: Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis and Echium

  4. Clinical evidence for individual animal therapy for papillomatous digital dermatitis (hairy heel wart) and infectious bovine pododermatitis (foot rot).

    PubMed

    Apley, Michael D

    2015-03-01

    Data supporting individual animal therapy for papillomatous digital dermatitis (PDD) and infectious pododermatitis (IP) in cattle are available for treatment with multiple drugs in the form of randomized, prospective clinical trials conducted in naturally occurring disease with negative controls and masked subjective evaluators. In the case of PDD, these trials support the use of topical tetracycline and oxytetracycline, lincomycin, a copper-containing preparation, and a nonantimicrobial cream. In individual therapy for IP, trial evidence is available to support systemic treatment with ceftiofur, florfenicol, tulathromycin, and oxytetracycline. However, it was not available for IP standards such as penicillin G, sulfadimethoxine, and tylosin. PMID:25705026

  5. 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

  6. 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

  7. Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells.

    PubMed

    Monsel, Antoine; Zhu, Ying-Gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W

    2014-11-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver, or brain. Genomic, proteomic, and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of promitotic, antiapoptotic, antiinflammatory, and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, the authors review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. (ANESTHESIOLOGY 2014; 121:1099-121). PMID:25211170

  8. Saw-scaled viper bites in Sri Lanka: is it a different subspecies? Clinical evidence from an authenticated case series.

    PubMed

    Gnanathasan, Ariaranee; Rodrigo, Chaturaka; Peranantharajah, Thambipillai; Coonghe, Anthonia

    2012-02-01

    The saw-scaled viper (SSV) (Echis carinatus) is considered to be a highly venomous snake in Sri Lanka despite any published clinical justification. Being a rarity, the clinical profile of SSV bites is not well established in Sri Lanka. We report a series of 48 (n-48) SSV bites from the Northern Province of Sri Lanka. The majority (65%) of victims had evidence of local envenoming at the site of the bite; however, 29% showed spontaneous bleeding and 71% had coagulopathy. There were no deaths in the series. The envenoming was mild in contrast to the mortality and significant morbidity associated with SSV bites in West Africa and some parts of India. These observations need to be further explored with laboratory studies to identify the venom components, study of morphological characteristics, and genetic profiling of the Sri Lankan SSV to see if it is different from the subspecies found elsewhere. PMID:22302858

  9. Renin-angiotensin system as a potential therapeutic target in stroke and retinopathy: experimental and clinical evidence.

    PubMed

    Fouda, Abdelrahman Y; Artham, Sandeep; El-Remessy, Azza B; Fagan, Susan C

    2016-02-01

    As our knowledge expands, it is now clear that the renin-angiotensin (Ang) system (RAS) mediates functions other than regulating blood pressure (BP). The RAS plays a central role in the pathophysiology of different neurovascular unit disorders including stroke and retinopathy. Moreover, the beneficial actions of RAS modulation in brain and retina have been documented in experimental research, but not yet exploited clinically. The RAS is a complex system with distinct yet interconnected components. Understanding the different RAS components and their functions under brain and retinal pathological conditions is crucial to reap their benefits. The aim of the present review is to provide an experimental and clinical update on the role of RAS in the pathophysiology and treatment of stroke and retinopathy. Combining the evidence from both these disorders allows a unique opportunity to move both fields forward. PMID:26769658

  10. Cell-based Therapy for Acute Organ Injury: Preclinical Evidence and On-going Clinical Trials Using Mesenchymal Stem Cells

    PubMed Central

    Monsel, Antoine; Zhu, Ying-gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W.

    2014-01-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. PMID:25211170

  11. Clinical Impact and Evidence Base for Physiotherapy in Treating Childhood Chronic Pain

    PubMed Central

    Amaria, Khush; Campbell, Fiona; McGrath, Patricia A.

    2011-01-01

    ABSTRACT Purpose: As part of the special series on pain, our objectives are to describe the key features of chronic pain in children, present the rationale for interdisciplinary treatment, report a case study based on our biopsychosocial approach, and highlight the integral role of physiotherapy in reducing children's pain and improving function. We also evaluate the evidence base supporting physiotherapy for treating chronic neuropathic pain in children. Summary of Key Points: Chronic pain affects many children and adolescents. Certain challenging pain conditions begin primarily during adolescence and disproportionately affect girls and women. Children with these conditions require an interdisciplinary treatment programme that includes physiotherapy as well as medication and/or psychological intervention. Converging lines of evidence from cohort follow-up studies, retrospective chart reviews, and one randomized controlled trial support the effectiveness of physiotherapy within an interdisciplinary programme for treating children with chronic pain. Conclusions: Evidence-based practice dictates that health care providers adopt clear guidelines for determining when treatments are effective and for identifying children for whom such treatments are most effective. Thus, additional well-designed trials are required to better identify the specific physiotherapy modalities that are most important in improving children's pain and function. PMID:22210976

  12. The use of corticosteroids in reducing cancer-related fatigue: assessing the evidence for clinical practice.

    PubMed

    Begley, Sarah; Rose, Kevin; O'Connor, Margaret

    2016-01-01

    Fatigue is a significant issue for people with advanced cancer, impacting on quality of life. Strategies to address fatigue encompass non-pharmacological and pharmacological approaches and thus require a multidisciplinary approach to manage the physical and psychological impacts on the individual. A widely used strategy to treat fatigue in palliative care is the use of corticosteroids but, despite being frequently prescribed, evidence of their effectiveness is ambiguous. This paper used a systematic approach to explore literature to determine evidence about whether the use of corticosteroids improves levels of cancer-related fatigue in people with advanced cancer. Some 12 relevant papers were found, of which all but 4 were excluded because of age, or because the population group was receiving active treatment. All studies reported improvements in patient-reported fatigue as a result of taking corticosteroids, although the quality of results varied and only a few were deemed to have statistically significant results. While there is some evidence that corticosteroids can improve cancer-related fatigue, more rigorous research is required. PMID:26804950

  13. 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. PMID:25231539

  14. 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 =10-3to10-5) 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.

  15. 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.

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

    PubMed

    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. PMID:24925357

  17. Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications.

    PubMed

    Lexchin, Joel

    2012-06-01

    Pharmaceutical companies fund the bulk of clinical research that is carried out on medications. Poor outcomes from these studies can have negative effects on sales of medicines. Previous research has shown that company funded research is much more likely to yield positive outcomes than research with any other sponsorship. The aim of this article is to investigate the possible ways in which bias can be introduced into research outcomes by drawing on concrete examples from the published literature. Poorer methodology in industry-funded research is not likely to account for the biases seen. Biases are introduced through a variety of measures including the choice of comparator agents, multiple publication of positive trials and non-publication of negative trials, reinterpreting data submitted to regulatory agencies, discordance between results and conclusions, conflict-of-interest leading to more positive conclusions, ghostwriting and the use of "seeding" trials. Thus far, efforts to contain bias have largely focused on more stringent rules regarding conflict-of-interest (COI) and clinical trial registries. There is no evidence that any measures that have been taken so far have stopped the biasing of clinical research and it's not clear that they have even slowed down the process. Economic theory predicts that firms will try to bias the evidence base wherever its benefits exceed its costs. The examples given here confirm what theory predicts. What will be needed to curb and ultimately stop the bias that we have seen is a paradigm change in the way that we treat the relationship between pharmaceutical companies and the conduct and reporting of clinical trials. PMID:21327723

  18. 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. PMID:26729681

  19. The biochemical basis and clinical evidence of food allergy due to lipid transfer proteins: a comprehensive review.

    PubMed

    Van Winkle, R Christopher; Chang, Christopher

    2014-06-01

    Plant lipid transfer proteins (LTPs) are ubiquitous proteins that are found in divergent plant species. Although the exact function of LTPs is not fully understood, LTPs are conserved across a broad range of plant species. Because LTPs share structural features, there is an increased probability for significant allergic cross-reactivity. The molecular features of LTPs also decrease the probability of degradation due to cooking or digestion, thereby increasing the probability of systemic absorption and severe allergic reactions. LTP allergy, unlike other forms of anaphylaxis, tends to occur more frequently in areas of lower latitude. The geographic distribution of LTP allergy, along with evidence of increased sensitization after respiratory exposure, has led to the hypothesis that LTP-related food allergy may be secondary to sensitization via the respiratory route. Clinical reactions associated with LTPs have broad clinical phenotypes and can be severe in nature. Life-threatening clinical reactions have been associated with ingestion of a multitude of plant products. Component-resolved diagnosis has played a significant role in research applications for LTP allergy. In the future, component-resolved diagnosis may play a significant role in day-to-day clinical care. Also, quantitative analysis of LTPs in foodstuffs may allow for the identification and/or production of low-LTP foods, thereby decreasing the risk to patients with LTP allergy. Furthermore, sublingual immunotherapy may provide a therapeutic option for patients with LTP allergy. PMID:23179517

  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. The Semantic Variant of Primary Progressive Aphasia: Clinical and Neuroimaging Evidence in Single Subjects

    PubMed Central

    Iaccarino, Leonardo; Crespi, Chiara; Della Rosa, Pasquale Anthony; Catricalà, Eleonora; Guidi, Lucia; Marcone, Alessandra; Tagliavini, Fabrizio; Magnani, Giuseppe; Cappa, Stefano F.; Perani, Daniela

    2015-01-01

    Background/Aim We present a clinical-neuroimaging study in a series of patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA), with the aim to provide clinical-functional correlations of the cognitive and behavioral manifestations at the single-subject level. Methods We performed neuropsychological investigations, 18F-FDG-PET single-subject and group analysis, with an optimized SPM voxel-based approach, and correlation analyses. A measurement of white matter integrity by means of diffusion tensor imaging (DTI) was also available for a subgroup of patients. Results Cognitive assessment confirmed the presence of typical semantic memory deficits in all patients, with a relative sparing of executive, attentional, visuo-constructional, and episodic memory domains. 18F-FDG-PET showed a consistent pattern of cerebral hypometabolism across all patients, which correlated with performance in semantic memory tasks. In addition, a majority of patients also presented with behavioral disturbances associated with metabolic dysfunction in limbic structures. In a subgroup of cases the DTI analysis showed FA abnormalities in the inferior longitudinal and uncinate fasciculi. Discussion Each svPPA individual had functional derangement involving an extended, connected system within the left temporal lobe, a crucial part of the verbal semantic network, as well as an involvement of limbic structures. The latter was associated with behavioral manifestations and extended beyond the area of atrophy shown by CT scan. Conclusion Single-subject 18F-FDG-PET analysis can account for both cognitive and behavioral alterations in svPPA. This provides useful support to the clinical diagnosis. PMID:25756991

  2. Clinical Correlates of Awareness for Balance, Function, and Memory: Evidence for the Modality Specificity of Awareness

    PubMed Central

    O'Connell, Megan E.; Crossley, Margaret; Morgan, Debra

    2014-01-01

    Awareness in dementia is increasingly recognized not only as multifactorial, but also as domain specific. We demonstrate differential clinical correlates for awareness of daily function, awareness of memory, and the novel exploration of awareness of balance. Awareness of function was higher for participants with mild cognitive impairment (aMCI and non-aMCI) than for those with dementia (due to Alzheimer disease; AD and non-AD), whereas awareness of memory was higher for both non-aMCI and non-AD dementia patients than for those with aMCI or AD. Balance awareness did not differ based on diagnostic subgroup. Awareness of function was associated with instrumental activities of daily living and caregiver burden. In contrast, awareness of balance was associated with fall history, balance confidence, and instrumental activities of daily living. Clinical correlates of awareness of memory depended on diagnostic group: associations held with neuropsychological variables for non-AD dementia, but for patients with AD dementia, depression and instrumental activities of daily living were clinical correlates of memory awareness. Together, these data provide support for the hypothesis that awareness and dementia are not unitary and are, instead, modality specific. PMID:24551452

  3. Virulence Diversity among Bacteremic Aeromonas Isolates: Ex Vivo, Animal, and Clinical Evidences

    PubMed Central

    Chen, Po-Lin; Wu, Chi-Jung; Tsai, Pei-Jane; Tang, Hung-Jen; Chuang, Yin-Ching; Lee, Nan-Yao; Lee, Ching-Chi; Li, Chia-Wen; Li, Ming-Chi; Chen, Chi-Chung; Tsai, Hung-Wen; Ou, Chun-Chun; Chen, Chang-Shi; Ko, Wen-Chien

    2014-01-01

    Background The objective of this study was to compare virulence among different Aeromonas species causing bloodstream infections. Methodology/Principal Findings Nine of four species of Aeromonas blood isolates, including A. dhakensis, A. hydrophila, A. veronii and A. caviae were randomly selected for analysis. The species was identified by the DNA sequence matching of rpoD. Clinically, the patients with A. dhakensis bacteremia had a higher sepsis-related mortality rate than those with other species (37.5% vs. 0%, P = 0.028). Virulence of different Aeromonas species were tested in C. elegans, mouse fibroblast C2C12 cell line and BALB/c mice models. C. elegans fed with A. dhakensis and A. caviae had the lowest and highest survival rates compared with other species, respectively (all P values <0.0001). A. dhakensis isolates also exhibited more cytotoxicity in C2C12 cell line (all P values <0.0001). Fourteen-day survival rate of mice intramuscularly inoculated with A. dhakensis was lower than that of other species (all P values <0.0001). Hemolytic activity and several virulence factor genes were rarely detected in the A. caviae isolates. Conclusions/Significance Clinical data, ex vivo experiments, and animal studies suggest there is virulence variation among clinically important Aeromonas species. PMID:25375798

  4. [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. PMID:23672116

  5. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence.

    PubMed

    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

  6. Killing of VRE Enterococcus faecalis by commensal strains: Evidence for evolution and accumulation of mobile elements in the absence of competition.

    PubMed

    Gaca, Anthony O; Gilmore, Michael S

    2016-01-01

    Enterococci are members of the gastrointestinal tract of humans and most animals that, over the past 3 decades, have emerged as leading causes of multidrug resistant hospital acquired infection (HAI). In addition to their general hardiness, many traits have entered enterococcal lineages through horizontal gene transfer, which has led to the evolution of pathogenic hospital-associated lineages uniquely adapted for survival and proliferation in the antibiotic perturbed ecology of the gastrointestinal tract. We recently observed that the accretion of mobile genetic elements in the prototype vancomycin resistant E. faecalis, clinical isolate V583, renders it unable to co-exist with native enterococci in healthy human fecal flora. In this addendum, we discuss how these findings inform our understanding of how multidrug resistant enterococci evolve, and the implications for the development of treatments that limit colonization and spread of highly antibiotic refractory microbes of this type. PMID:26939857

  7. 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

  8. 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

  9. 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. PMID:26009665

  10. Evidence-Based Approach to Fiber Supplements and Clinically Meaningful Health Benefits, Part 1

    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. The first part (current issue) of this 2-part series will focus on 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 (next 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:25972618

  11. 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.

  12. Considering specific clinical features as evidence of pathogenic copy number variants.

    PubMed

    Preiksaitiene, Egle; Molytė, Alma; Kasnauskiene, Jurate; Ciuladaite, Zivile; Utkus, Algirdas; Patsalis, Philippos C; Kučinskas, Vaidutis

    2014-05-01

    Since the introduction of high-resolution microarray technologies, it has become apparent that structural chromosomal rearrangements can lead to a wide variety of clinical manifestations, including developmental delay/intellectual disability (DD/ID). It has been shown previously that the diagnostic yield of genome-wide array-based identification of submicroscopic alterations in patients with ID varies widely and depends on the patient selection criteria. More attempts have recently been made to define the phenotypic clues of pathogenic copy number variants (CNVs). The aim of this study was to investigate a well-phenotyped cohort of patients with DD/ID and determine whether certain clinical features may serve as indicators for pathogenic CNVs. A retrospective analysis was conducted for patients with DD/ID (n = 211) who were tested using genome-wide chromosomal microarray technologies and a review of the clinical data was performed. Pathogenic CNVs were detected in 29 patients. In comparison with individuals who had normal molecular karyotyping results (n = 182), malformations of the musculoskeletal system; congenital malformations of the CNS (particularly hydrocephalus and congenital malformations of the corpus callosum); minor anomalies of the eye, face, and neck subgroup (particularly downward-slanting palpebral fissures, minor anomalies of the ear, and micrognathia); brachydactyly; and umbilical hernia were more common in patients with chromosomal alterations. A multivariate logistic regression analysis allowed the identification of three independent pathogenic CNV predictors: congenital malformations of the corpus callosum, minor anomalies of the ear, and brachydactyly. Insights into the chromosomal phenotype may help to increase the diagnostic yield of microarray technologies and sharpen the distinction between chromosomal alterations and other conditions. PMID:24535828

  13. RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms.

    PubMed

    Randhawa, Puneet Kaur; Bali, Anjana; Jaggi, Amteshwar Singh

    2015-01-01

    Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. This cycle is repeated for 3-4 consecutive periods to precondition the tissue and improve the survival. The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked β-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC. PMID:25176179

  14. 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

  15. Development of an Evidence-Based Clinical Algorithm for Practice in Hypotonia Assessment: A Proposal

    PubMed Central

    2014-01-01

    Background Assessing muscle tone in children is essential during the neurological assessment and is often essential in ensuring a more accurate diagnosis for appropriate management. While there have been advances in child neurology, there remains much contention around the subjectivity of the clinical assessment of hypotonia, which is often the first step in the diagnostic process. Objective In response to this challenge, the objective of the study is to develop and validate a prototype of a decision making process in the form of a clinical algorithm that will guide clinicians during this assessment process. Methods Design research within a pragmatic stance will be employed in this study. Multi-phase stages of assessment, prototyping and evaluation will occur. These will include processes that include a systematic review, processes of reflection and action as well as validation methods. Given the mixed methods nature of this study, use of NVIVO or ATLAS-ti will be used in the analysis of qualitative data and SPSS for quantitative data. Results Initial results from the systematic review revealed a paucity of scientific literature that documented the objective assessment of hypotonia in children. The review identified the need for more studies with greater methodological rigor in order to determine best practice with respect to the methods used in the assessment of low muscle tone in the paediatric population. Conclusions It is envisaged that this proposal will contribute to a more accurate clinical diagnosis of children with low muscle tone in the absence of a gold standard. We anticipate that the use of this tool will ultimately assist clinicians towards moving to evidenced based practice whilst upholding best practice in the care of children with hypotonia. PMID:25485571

  16. Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.

    PubMed

    Bruehl, Stephen; Maihöfner, Christian; Stanton-Hicks, Michael; Perez, Roberto S G M; Vatine, Jean-Jacques; Brunner, Florian; Birklein, Frank; Schlereth, Tanja; Mackey, Sean; Mailis-Gagnon, Angela; Livshitz, Anatoly; Harden, R Norman

    2016-08-01

    Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury. PMID:27023422

  17. 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