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Sample records for accumulating clinical evidence

  1. Sequential biases in accumulating evidence

    PubMed Central

    Huggins, Richard; Dogo, Samson Henry

    2015-01-01

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

  2. Evidence of clinical competence.

    PubMed

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

    2012-06-01

    This cross-sectional research used a qualitative questionnaire to explore clinical competence in nursing. The aim was to look for evidence of how clinical competence showed itself in practice. In the research, the views from both education and working life are combined to broadly explore and describe clinical competence from the perspective of students, clinical preceptors and teachers. The questions were formulated on how clinical competence is characterised and experienced, what contributes to it and how it is maintained, and on the relation between clinical competence and evidence-based care. The answers were analysed by inductive content analysis. The results showed that clinical competence in practice is encountering, knowing, performing, maturing and improving. Clinical competence is an ongoing process, rather than a state and manifests itself in an ontological and a contextual dimension.

  3. Evidence Accumulation in the Magnitude System

    PubMed Central

    Lambrechts, Anna; Walsh, Vincent; van Wassenhove, Virginie

    2013-01-01

    Perceptual interferences in the estimation of quantities (time, space and numbers) have been interpreted as evidence for a common magnitude system. However, if duration estimation has appears sensitive to spatial and numerical interferences, space and number estimation tend to be resilient to temporal manipulations. These observations question the relative contribution of each quantity in the elaboration of a representation in a common mental metric. Here, we elaborated a task in which perceptual evidence accumulated over time for all tested quantities (space, time and number) in order to match the natural requirement for building a duration percept. For this, we used a bisection task. Experimental trials consisted of dynamic dots of different sizes appearing progressively on the screen. Participants were asked to judge the duration, the cumulative surface or the number of dots in the display while the two non-target dimensions varied independently. In a prospective experiment, participants were informed before the trial which dimension was the target; in a retrospective experiment, participants had to attend to all dimensions and were informed only after a given trial which dimension was the target. Surprisingly, we found that duration was resilient to spatial and numerical interferences whereas space and number estimation were affected by time. Specifically, and counter-intuitively, results revealed that longer durations lead to smaller number and space estimates whether participants knew before (prospectively) or after (retrospectively) a given trial which quantity they had to estimate. Altogether, our results support a magnitude system in which perceptual evidence for time, space and numbers integrate following Bayesian cue-combination rules. PMID:24339998

  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. Evidence accumulation as a model for lexical selection.

    PubMed

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

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. PMID:26375509

  8. 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

  9. 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

  10. 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.

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

    PubMed

    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.

  13. 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

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2008-10-07

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

  17. 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

  18. What is value-accumulated reward or evidence?

    PubMed

    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.

  19. Exogenous glutamine: the clinical evidence.

    PubMed

    Bongers, Thomas; Griffiths, Richard D; McArdle, Anne

    2007-09-01

    We know that critically ill patients suffering from undernutrition with a limited nutritional reserve have a poorer outcome. Furthermore, having a low body mass index has been shown to be an independent predictor of excess mortality in multiple organ failure. Therefore, nutritional support has gained increasing interest in critical illness with the hope of preventing or attenuating the effects of malnutrition. A negative nitrogen balance is the characteristic metabolic feature in critical illness, with the major protein loss derived from skeletal muscle. In particular, glutamine concentrations are rapidly reduced in plasma and muscle. Over the last 20 yrs or so, increasing evidence is emerging to support the use of glutamine supplementation in critical illness. Clinical trials have found a mortality and morbidity advantage with glutamine supplementation. The advantage appears to be greater the more glutamine is given and greater again when given parenterally. Various modes of action have been postulated. Glutamine seems to have an effect on the immune system, antioxidant status, glucose metabolism, and heat shock protein response. However, the benefit of exogenous glutamine on morbidity and mortality is not universally accepted. This review critically appraises the current clinical evidence regarding glutamine supplementation in critical illness.

  20. 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.

  1. 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

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

    PubMed

    Takahashi, Masanobu

    2016-06-01

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

  3. 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

  4. 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

  5. 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.

  6. Action Planning and the Timescale of Evidence Accumulation.

    PubMed

    Tsetsos, Konstantinos; Pfeffer, Thomas; Jentgens, Pia; 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-motor contingencies

  7. Neurodegeneration with brain iron accumulation - clinical syndromes and neuroimaging.

    PubMed

    Schipper, Hyman M

    2012-03-01

    Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this article, we discuss seven NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are Friedreich ataxia (FA), pantothenate kinase 2-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Kufor-Rakeb disease (KRD), aceruloplasminemia, and neuroferritinopathy. An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

  8. The accumulated evidence on lung cancer and environmental tobacco smoke.

    PubMed Central

    Hackshaw, A. K.; Law, M. R.; Wald, N. J.

    1997-01-01

    OBJECTIVE: To estimate the risk of lung cancer in lifelong non-smokers exposed to environmental tobacco smoke. DESIGN: Analysis of 37 published epidemiological studies of the risk of lung cancer (4626 cases) in non-smokers who did and did not live with a smoker. The risk estimate was compared with that from linear extrapolation of the risk in smokers using seven studies of biochemical markers of tobacco smoke intake. MAIN OUTCOME MEASURE: Relative risk of lung cancer in lifelong non-smokers according to whether the spouse currently smoked or had never smoked. RESULTS: The excess risk of lung cancer was 24% (95% confidence interval 13% to 36%) in non-smokers who lived with a smoker (P < 0.001). Adjustment for the effects of bias (positive and negative) and dietary confounding had little overall effect; the adjusted excess risk was 26% (7% to 47%). The dose-response relation of the risk of lung cancer with both the number of cigarettes smoked by the spouse and the duration of exposure was significant. The excess risk derived by linear extrapolation from that in smokers was 19%, similar to the direct estimate of 26%. CONCLUSION: The epidemiological and biochemical evidence on exposure to environmental tobacco smoke, with the supporting evidence of tobacco specific carcinogens in the blood and urine of non-smokers exposed to environmental tobacco smoke, provides compelling confirmation that breathing other people's tobacco smoke is a cause of lung cancer. PMID:9365295

  9. 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…

  10. 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

  11. 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

  12. Error awareness as evidence accumulation: effects of speed-accuracy trade-off on error signaling

    PubMed Central

    Steinhauser, Marco; Yeung, Nick

    2012-01-01

    Errors in choice tasks have been shown to elicit a cascade of characteristic components in the human event-related potential (ERPs)—the error-related negativity (Ne/ERN) and the error positivity (Pe). Despite the large number of studies concerned with these components, it is still unclear how they relate to error awareness as measured by overt error signaling responses. In the present study, we considered error awareness as a decision process in which evidence for an error is accumulated until a decision criterion is reached, and hypothesized that the Pe is a correlate of the accumulated decision evidence. To test the prediction that the amplitude of the Pe varies as a function of the strength and latency of the accumulated evidence for an error, we manipulated the speed-accuracy trade-off (SAT) in a brightness discrimination task while participants signaled the occurrence of errors. Based on a previous modeling study, we predicted that lower speed pressure should be associated with weaker evidence for an error and, thus, with smaller Pe amplitudes. As predicted, average Pe amplitude was decreased and error signaling was impaired in a low speed pressure condition compared to a high speed pressure condition. In further analyses, we derived single-trial Pe amplitudes using a logistic regression approach. Single-trial amplitudes robustly predicted the occurrence of signaling responses on a trial-by-trial basis. These results confirm the predictions of the evidence accumulation account, supporting the notion that the Pe reflects accumulated evidence for an error and that this evidence drives the emergence of error awareness. PMID:22905027

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Treatment of intracerebral hemorrhage: the clinical evidences.

    PubMed

    Sterzi, R; Vidale, S

    2004-03-01

    Of all strokes 10% to 15% are intracerebral hemorrhage, primary ICH accounting for more than 75% of cases. A correct evaluation and management must start in the emergency room, in particular for patients who rapidly deteriorate. The diffusion of organized care for stroke patients and the availability of the stroke units in Italian hospitals, may represent a further opportunity to improve the outcome of patients with ICH. Despite the bulk of evidences coming from the randomized clinical therapeutic trials for acute ischemic stroke, the available data for randomized surgical trials are scanty. In these small randomized studies, neither surgical nor medical treatment has conclusively been shown to benefit patients with ICH. Surgical techniques are improving but it is important to find out the time window during which surgical evacuation is most effective with respect to the long-term outcome. The use of thrombolytic therapy to promote the resolution of ventricular blood clots appears to be promising.

  19. 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

  20. 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

  1. 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.

  2. Mental Exercises for Cognitive Function: Clinical Evidence

    PubMed Central

    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

  3. Identification of Novel Clinical Factors Associated with Hepatic Fat Accumulation in Extreme Obesity

    PubMed Central

    Gerhard, Glenn S.; Benotti, Peter; Chu, Xin; Strodel, William E.; Gabrielsen, Jon D.; Ibele, Anna; Still, Christopher D.

    2014-01-01

    Objectives. The accumulation of lipids stored as excess triglycerides in the liver (steatosis) is highly prevalent in obesity and has been associated with several clinical characteristics, but most studies have been based on relatively small sample sizes using a limited set of variables. We sought to identify clinical factors associated with liver fat accumulation in a large cohort of patients with extreme obesity. Methods. We analyzed 2929 patients undergoing intraoperative liver biopsy during a primary bariatric surgery. Univariate and multivariate regression modeling was used to identify associations with over 200 clinical variables with the presence of any fat in the liver and with moderate to severe versus mild fat accumulation. Results. A total of 19 data elements were associated with the presence of liver fat and 11 with severity of liver fat including ALT and AST, plasma lipid, glucose, and iron metabolism variables, several medications and laboratory measures, and sleep apnea. The accuracy of a multiple logistic regression model for presence of liver fat was 81% and for severity of liver fat accumulation was 77%. Conclusions. A limited set of clinical factors can be used to model hepatic fat accumulation with moderate accuracy and may provide potential mechanistic insights in the setting of extreme obesity. PMID:25610640

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  6. 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

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

    PubMed

    Brancato, Vera C

    2006-01-01

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

  8. 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.

  9. 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

  10. 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

  11. First evidence of accumulation in cyanobacteria of guanidinoacetate, a precursor of the toxin cylindrospermopsin.

    PubMed

    Barón-Sola, Ángel; Sanz-Alférez, Soledad; del Campo, Francisca F

    2015-01-01

    Guanidinoacetate (GAA) is one of the most extensively studied toxic guanidine compounds. Changes in GAA can affect the nervous system and induce hyperhomocysteinemia, representing a risk factor for cardiovascular diseases. In cyanobacteria, GAA is thought to be an intermediate in the synthesis of the toxin cylindrospermopsin (CYN), one of the most common known cyanotoxins that affects multiple organs and functions in animals and plants. In spite of the evidence supporting GAA toxicity and its role in CYN synthesis, no data have been reported on the accumulation of GAA in any cyanobacterium. We have analyzed and compared the content of GAA in cultures of diverse cyanobacteria types, both cylindrospermopsin producing (CYN(+)) and not producing (CYN(-)). The results obtained show that GAA accumulates in the majority of the strains tested, although the highest content was found in one of the CYN(+) strain, Aphanizomenon ovalisporum UAM-MAO. In this strain, both GAA and CYN can be located within and out the cells. In conclusion, GAA appears to be a general cyanobacterial metabolite that due to its proven toxic should be considered when studying and managing cyanobacteria toxicity.

  12. A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.

    PubMed

    Salomão, Rubens Paulo Araújo; Pedroso, José Luiz; Gama, Maria Thereza Drumond; Dutra, Lívia Almeida; Maciel, Ricardo Horta; Godeiro-Junior, Clécio; Chien, Hsin Fen; Teive, Hélio A G; Cardoso, Francisco; Barsottini, Orlando G P

    2016-07-01

    Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

  13. Pharmacotherapy of urolithiasis: evidence from clinical trials.

    PubMed

    Moe, Orson W; Pearle, Margaret S; Sakhaee, Khashayar

    2011-02-01

    Urolithiasis is a worldwide problem with significant health and economic burdens. Medical therapy that alters the course of stone disease has enormous medical and financial impact. Urolithiasis is a final manifestation of a broad range of etiologies and pathogenesis. The modest progress in understanding the pathophysiology has hampered successful development of targeted therapy. Current regimens are based mostly on rational alteration of urinary biochemistry and physical chemistry to lower the risk of precipitation. In terms of pharmacotherapy, there are drugs to successfully improve hypercalciuria, hypocitraturia, aciduria, hyperuricosuria, and hypercystinuria. These agents have been proven to be effective in randomized controlled trials in improving urinary biochemical and physicochemical risk factors, as well as clinical outcomes. Although our current regimens have clearly improved the management and lives of stone formers, there are still clearly identifiable immense voids in the knowledge of pathophysiology of stone disease that can be filled with combined basic science and clinical studies. PMID:20927039

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

    PubMed

    Lee, Michael D; Cummins, Tarrant D R

    2004-04-01

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

  15. ART-EMAP: A neural network architecture for object recognition by evidence accumulation.

    PubMed

    Carpenter, G A; Ross, W D

    1995-01-01

    A new neural network architecture is introduced for the recognition of pattern classes after supervised and unsupervised learning. Applications include spatio-temporal image understanding and prediction and 3D object recognition from a series of ambiguous 2D views. The architecture, called ART-EMAP, achieves a synthesis of adaptive resonance theory (ART) and spatial and temporal evidence integration for dynamic predictive mapping (EMAP). ART-EMAP extends the capabilities of fuzzy ARTMAP in four incremental stages. Stage 1 introduces distributed pattern representation at a view category field. Stage 2 adds a decision criterion to the mapping between view and object categories, delaying identification of ambiguous objects when faced with a low confidence prediction. Stage 3 augments the system with a field where evidence accumulates in medium-term memory. Stage 4 adds an unsupervised learning process to fine-tune performance after the limited initial period of supervised network training. Each ART-EMAP stage is illustrated with a benchmark simulation example, using both noisy and noise-free data. PMID:18263371

  16. Current penile-rehabilitation strategies: Clinical evidence.

    PubMed

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

    2013-09-01

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

  17. 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…

  18. 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.

  19. 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

  20. Precision and neuronal dynamics in the human posterior parietal cortex during evidence accumulation

    PubMed Central

    FitzGerald, Thomas H.B.; Moran, Rosalyn J.; Friston, Karl J.; Dolan, Raymond J.

    2015-01-01

    Primate studies show slow ramping activity in posterior parietal cortex (PPC) neurons during perceptual decision-making. These findings have inspired a rich theoretical literature to account for this activity. These accounts are largely unrelated to Bayesian theories of perception and predictive coding, a related formulation of perceptual inference in the cortical hierarchy. Here, we tested a key prediction of such hierarchical inference, namely that the estimated precision (reliability) of information ascending the cortical hierarchy plays a key role in determining both the speed of decision-making and the rate of increase of PPC activity. Using dynamic causal modelling of magnetoencephalographic (MEG) evoked responses, recorded during a simple perceptual decision-making task, we recover ramping-activity from an anatomically and functionally plausible network of regions, including early visual cortex, the middle temporal area (MT) and PPC. Precision, as reflected by the gain on pyramidal cell activity, was strongly correlated with both the speed of decision making and the slope of PPC ramping activity. Our findings indicate that the dynamics of neuronal activity in the human PPC during perceptual decision-making recapitulate those observed in the macaque, and in so doing we link observations from primate electrophysiology and human choice behaviour. Moreover, the synaptic gain control modulating these dynamics is consistent with predictive coding formulations of evidence accumulation. PMID:25512038

  1. Evidence from Clinical Trials: Can We Do Better?

    PubMed Central

    Siderowf, Andrew D.

    2004-01-01

    Summary: Randomized clinical trials provide the most internally valid evidence for medical decision-making. In many areas of neurology, results from clinical trials showing which therapies are and are not effective have had a substantial impact on patient care. Relative to observational methods, the central advantage of clinical trials is control of bias attributable to unmeasured differences between patients. However, trials also have clear limitations, including a historical failure to include a representative cross-section of patients with a given disease, and highly structured treatment regimes that are difficult to replicate in normal practice settings. These limitations tend to reduce the generalizability of results from clinical trials. This article reviews some ways in which the design and application of clinical trials could be improved so that the evidence produced would be more relevant to health-care providers and other decision makers. PMID:15717039

  2. 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

  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. 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.

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

    PubMed Central

    2011-01-01

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

  6. Finding the common core: evidence-based practices, clinically relevant evidence, and core mechanisms of change.

    PubMed

    Sexton, Thomas L; Kelley, Susan Douglas

    2010-03-01

    Improving the quality of children's mental health care can benefit from the adoption of evidence based and evidence informed treatments. However, the promise of moving science into practice is hampered by three core elements that need to be addressed in the current conversation among key stakeholders: (1) expanding our understanding of the clinical relevance of different types of evidence, (2) emphasizing the identification of core mechanisms of change, and (3) re-conceptualizing what evidence-based practice means. This paper focuses on these elements in an attempt to find a common core among stakeholders that may create opportunities for more inclusive conversation to move the field of children's mental health care forward.

  7. 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.

  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. GRADE the evidence before using the results in clinical practice.

    PubMed

    Tharyan, Prathap

    2011-01-01

    Reports of clinical trials that do not describe the methods used to minimise the risk of bias, and reports that do not present results in a comprehensible and accurate manner, are unethical as they could lead to misleading conclusions, adverse health outcomes, and the inappropriate use of healthcare resources. The Grading of Recommendations: Assessment, Development, and Evaluation (GRADE) approach to framing healthcare recommendations provides a pragmatic approach to making summary evidence profiles of outcome-specific evaluations regarding the magnitude and precision of estimates of benefit and harms, and the overall quality of evidence from comparisons of healthcare interventions. In addition, contextual factors such as the balance between benefits, harms, and resource costs; baseline risks in different groups; inconveniences; varying values and preferences; and competing priorities and options, should ideally be extrapolated from these evidence profiles and other sources of evidence to determine the strength of recommendations regarding the use of an intervention.

  11. 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.

  12. Accessing heterogeneous sources of evidence to answer clinical questions.

    PubMed

    Mendonça, E A; Cimino, J J; Johnson, S B; Seol, Y H

    2001-04-01

    The large and rapidly growing number of information sources relevant to health care, and the increasing amounts of new evidence produced by researchers, are improving the access of professionals and students to valuable information. However, seeking and filtering useful, valid information can be still very difficult. An online information system that conducts searches based on individual patient data can have a beneficial influence on the particular patient's outcome and educate the healthcare worker. In this paper, we describe the underlying model for a system that aims to facilitate the search for evidence based on clinicians' needs. This paper reviews studies of information needs of clinicians, describes principles of information retrieval, and examines the role that standardized terminologies can play in the integration between a clinical system and literature resources, as well as in the information retrieval process. The paper also describes a model for a digital library system that supports the integration of clinical systems with online information sources, making use of information available in the electronic medical record to enhance searches and information retrieval. The model builds on several different, previously developed techniques to identify information themes that are relevant to specific clinical data. Using a framework of evidence-based practice, the system generates well-structured questions with the intent of enhancing information retrieval. We believe that by helping clinicians to pose well-structured clinical queries and including in them relevant information from individual patients' medical records, we can enhance information retrieval and thus can improve patient-care.

  13. 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

  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.

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

    PubMed Central

    Saha, Sabyasachi; Singh, Sanjay

    2016-01-01

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

  17. Experimental evidence for the accumulation of egg pigment in the brain cavities of Xenopus tadpoles.

    PubMed

    Kordylewski, L

    1983-07-01

    The origin and fate of darkly pigmented clusters of cells that float freely in the brain cavities of the tadpoles of Xenopus laevis have been experimentally investigated. The results point to the conclusion that the clusters are the sites of egg pigment accumulation, which remain within the brain cavities or at its walls until metamorphosis.

  18. Analysis of storage lipid accumulation in Alcanivorax borkumensis: Evidence for alternative triacylglycerol biosynthesis routes in bacteria.

    PubMed

    Kalscheuer, Rainer; Stöveken, Tim; Malkus, Ursula; Reichelt, Rudolf; Golyshin, Peter N; Sabirova, Julia S; Ferrer, Manuel; Timmis, Kenneth N; Steinbüchel, Alexander

    2007-02-01

    Marine hydrocarbonoclastic bacteria, like Alcanivorax borkumensis, play a globally important role in bioremediation of petroleum oil contamination in marine ecosystems. Accumulation of storage lipids, serving as endogenous carbon and energy sources during starvation periods, might be a potential adaptation mechanism for coping with nutrient limitation, which is a frequent stress factor challenging those bacteria in their natural marine habitats. Here we report on the analysis of storage lipid biosynthesis in A. borkumensis strain SK2. Triacylglycerols (TAGs) and wax esters (WEs), but not poly(hydroxyalkanoic acids), are the principal storage lipids present in this and other hydrocarbonoclastic bacterial species. Although so far assumed to be a characteristic restricted to gram-positive actinomycetes, substantial accumulation of TAGs corresponding to a fatty acid content of more than 23% of the cellular dry weight is the first characteristic of large-scale de novo TAG biosynthesis in a gram-negative bacterium. The acyltransferase AtfA1 (ABO_2742) exhibiting wax ester synthase/acyl-coenzyme A:diacylglycerol acyltransferase (WS/DGAT) activity plays a key role in both TAG and WE biosynthesis, whereas AtfA2 (ABO_1804) was dispensable for storage lipid formation. However, reduced but still substantial residual TAG levels in atfA1 and atfA2 knockout mutants compellingly indicate the existence of a yet unknown WS/DGAT-independent alternative TAG biosynthesis route. Storage lipids of A. borkumensis were enriched in saturated fatty acids and accumulated as insoluble intracytoplasmic inclusions exhibiting great structural variety. Storage lipid accumulation provided only a slight growth advantage during short-term starvation periods but was not required for maintaining viability and long-term persistence during extended starvation phases. PMID:17122340

  19. 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

  20. 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

  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. 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.

  3. 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

  4. 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

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

    PubMed

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

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

  6. 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.

  7. 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.

  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. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities.

    PubMed

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

    2014-12-01

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

  10. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities.

    PubMed

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

    2014-12-01

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

  11. First evidence of accumulation of mega boulders on the Mediterranean rocky coast of Provence (southern France)

    NASA Astrophysics Data System (ADS)

    Vella, C.; Demory, F.; Canut, V.; Dussouillez, P.; Fleury, T. J.

    2011-03-01

    An accumulation of boulders was recently discovered along the rocky coast of the Gulf of Fos located in Provence, in an area exposed to a south-westerly wave regime. The coast around this locality forms the western extremity of the calcareous Nerthe range between Marseille and the Rhône Delta. Several mega blocks are scattered to a distance of 30 m behind the coast line. The largest block (33.5 tonnes) has been transported about 39 m inland, up to about 2 m a.s.l. On the Mediterranean coast, the origin of such blocks is often attributed to tsunami-generated waves, but in the case examined here, although the origin is unclear, the differences in surface state between boulders indicates several events generated by south-westerly storms. Radiocarbon dating on several different shells collected from seven different boulders yields a wide dispersion of ages ranging from 4000 BP to the Modern Period. The differences in surface appearance, as well as the differences of fauna conservation and surface coloration, in some cases in a very fresh state, along with the dispersion of radiocarbon ages, suggest that historic storm events have affected these megablocks.

  12. No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

    PubMed Central

    Joyner-Matos, Joanna; Bean, Laura C.; Richardson, Heidi L.; Sammeli, Tammy; Baer, Charles F.

    2011-01-01

    Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the mutagenic effects of oxidative stress in C. elegans are minor relative to the effects of other types of mutations, such as errors during DNA replication. However, mev-1 MA lines did go extinct more frequently than wild-type lines; some possible explanations for the difference in extinction rate are discussed. PMID:21979932

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

    PubMed

    Gopal, Atul; Murthy, Aditya

    2015-09-01

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

  14. 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.

  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. 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

  17. Evidence-based clinical practice guidelines for irritable bowel syndrome.

    PubMed

    Fukudo, Shin; Kaneko, Hiroshi; Akiho, Hirotada; Inamori, Masahiko; Endo, Yuka; Okumura, Toshikatsu; Kanazawa, Motoyori; Kamiya, Takeshi; Sato, Ken; Chiba, Toshimi; Furuta, Kenji; Yamato, Shigeru; Arakawa, Tetsuo; Fujiyama, Yoshihide; Azuma, Takeshi; Fujimoto, Kazuma; Mine, Tetsuya; Miura, Soichiro; Kinoshita, Yoshikazu; Sugano, Kentaro; Shimosegawa, Tooru

    2015-01-01

    New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world. PMID:25500976

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

    PubMed

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

    2012-01-01

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

  19. Evidence of clinically relevant efficacy for dietary supplements and nutraceuticals.

    PubMed

    Cicero, Arrigo F G; Borghi, Claudio

    2013-06-01

    Beyond the well-known effects on blood pressure (BP) of the DASH and the Mediterranean diets, a large number of studies have investigated the possible a BP-lowering effect from different dietary supplements and nutraceuticals, mostly antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence support the use of potassium, L-arginine, vitamin C, cocoa flavonoids, coenzyme Q10, controlled-release melatonin, and aged garlic extract. However there is a need for data about the long-term safety of a large part of these products. Moreover, further clinical research is advisable to identify between the available active nutraceuticals and those with the best cost-effectiveness and risk-benefit ratio for widespread use in a general population with low added cardiovascular risk related to uncomplicated hypertension. PMID:23430658

  20. Geochemical evidence for modern sediment accumulation on the continental shelf off southern New England

    USGS Publications Warehouse

    Bothner, Michael H.; Spiker, E. C.; Johnson, P. P.; Rendigs, R. R.; Aruscavage, P. J.

    1981-01-01

    An area of fine-grained sediment approximately 170 km x 74 km in size, located in water depths between 60 m and 150 m, south of Martha's Vineyard, Mass., is a site of modern sediment deposition. The 14C ages systematically increase with sediment depth from about 1,300 years B.P. at the surface to 8,000-10,000 years B.P. at the depth of maximum core penetration. The old age for the surface sediments probably results from a combination of deposition of old carbon and faunal mixing. In the finest sediments, the sedimentation rates were approximately 130 cm/1,000 yrs when deposition began and have decreased to about 25 cm/1,000 yrs. The decreasing sedimentation rate reflects a diminishing source of fine sediments, which presumably came from the Georges Bank and Nantucket Shoals area. Inventories of excess 210Pb in undisturbed cores average 70 dpm/cm2 (disintegrations per minute per square centimeter), more than two times higher than the flux of 210Pb from the atmosphere and from 226Ra decay in the overlying water. This additional influx of 210Pb either must be with new fine-grained sediment material or from solutions that are stripped of their 210Pb by particulates in the bottom nepheloid layer. Stable Pb concentrations in surface sediments are about 28 ppm, as much as two times higher than concentrations at depth. The high accumulation rates, 210Pb inventories, and trace-metal profiles imply that this area is a modern sink for fine-grained sediments and for pollutants associated with particulate matter in the water column. To our knowledge, this is the only site of present-day natural deposition on the Continental Shelf off the eastern United States, exclusive of the Gulf of Maine. Because the net currents on the outer half of this Continental Shelf flow from northeast to southwest, this fine-grained deposit may receive its sediments and possible contaminants from the Nantucket Shoals and Georges Bank regions.

  1. 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

  2. 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

  3. [Ethical problems in clinical practice of evidence-based medicine].

    PubMed

    Rogler, G; Fröhlich, G

    2009-07-01

    Ethical problems as consequences of evidence-based medicine (EBM) have insufficiently been investigated and discussed. EBM--as initially intended--is usually interpreted as an attempt to treat patients individually with respect to their personal preferences and the present situation according to the best available clinical evidence. This practice is in line with accepted medical ethics. Therefore, it does not appear to be a relevant issue for discussion at first sight. However, between the theoretical concept and the practical use (or misuse) of this approach discrepancies exist which require some considerations. In particular the practical use of EBM generates a number of ethical problems: EBM is increasingly misused as an instrument of resource-allocation. Based on randomized controlled trials (RCTs) for very specific patient groups, the general access to medical supply is regulated and limited. The recurrence to general ("supra-individual") external evidence may additionally be in strong contrast to the individual patients' intentions and will and leads to conflicts for therapy decisions. If no longer the individual preferences and the patients' will are in the center of therapy decisions but a so called "general welfare", the mutual trust between patient and doctor is eroded. The utilitaristic approach of a primacy of this general welfare in opposition to the individual welfare is favored by the present interpretation and use of EBM. This conflicts with the perception of the doctor as a patient's advocate. However, the doctor being the patient's advocate is the basis of the traditional medical ethos. We should take care that we do not completely lose the basis of our medical ethos.

  4. Accumulating evidence supports a taste component for free fatty acids in humans.

    PubMed

    Mattes, Richard D

    2011-09-26

    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.

  5. 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

  6. 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

  7. Characterization of methadone overdose: clinical considerations and the scientific evidence.

    PubMed

    Wolff, Kim

    2002-08-01

    Overdosing with methadone is a growing phenomenon in Britain and other countries due to the increase in prescription and the availability of this compound. Little is known of the circumstances surrounding methadone death due to some extent to the difficulty of defining drug-related death and also the difficulty of collecting clinical and biographical data in a predominantly illegal and marginal milieu. However, the evidence points to highest risk at night (to this end manifestations of its toxicity often go unrecognized) in those whose usual tolerance has been reduced and occurring some considerable time after ingestion. Further investigations are needed to elucidate fully the mechanism and spectrum of methadone overdose. Death from methadone is eminently preventable more so because of the long-term nature of the clinical sequelae. Indeed the key issue with methadone that sets it apart from other opioids is its potential for delayed toxicity. Consequently steps should be taken to disseminate the salient facts to all those who come into contact with the drug.

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

    PubMed

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

    2014-01-01

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

  9. Weaning from mechanical ventilation: the evidence from clinical research.

    PubMed

    Meade, M O; Guyatt, G H; Cook, D J

    2001-12-01

    Mechanical ventilation incurs substantial morbidity, mortality, and costs. Both premature extubation and delayed extubation can cause harm. Therefore, weaning that is both expeditious and safe is highly desirable. The purpose of this review is to summarize the literature related to weaning modes, spontaneous breathing trials, weaning predictors, weaning with noninvasive positive pressure ventilation, and weaning protocols. We used 5 computerized databases and a duplicate independent review process to select articles for this review. We included randomized clinical trials evaluating any weaning interventions and nonrandomized trials of weaning predictors, with a focus on studies reporting clinically important outcomes. We abstracted quantitative data using several metrics and pooled results across studies only when our assessment of the patients, interventions, and outcomes indicated that pooling was legitimate. The available clinical research evidence suggests that, for progressive weaning of the level of mechanical support, it may be best to choose modes other than synchronized intermittent mandatory ventilation and it is unreasonable to be dogmatic about the use of other modes. There may also be substantial benefits to early extubation with back-up institution of noninvasive positive pressure ventilation, as needed, though this remains an experimental approach. For trials of spontaneous breathing, low levels of pressure support may hasten extubation. We did not uncover any consistently powerful weaning predictors, suggesting that formal use of predictors in patients being considered for reduction or discontinuation of mechanical support is unlikely to improve patient care. The likely explanation is that clinicians already fully consider information from weaning predictors in choosing patients for trials of reduction or discontinuation of mechanical ventilation. Finally, implementation of respiratory therapist- or nurse-driven protocols may be useful for all

  10. 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

  11. 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

  12. 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…

  13. Clinical evidence of pharmacokinetic changes in thalidomide therapy.

    PubMed

    Nakamura, Katsunori; Matsuzawa, Naoki; Ohmori, Shigeru; Ando, Yuichi; Yamazaki, Hiroshi; Matsunaga, Tamihide

    2013-01-01

    The teratogenic effects of thalidomide have been studied for more than 50 years. However, there have been few studies of the pharmacokinetic changes occurring during thalidomide therapy. Thalidomide was originally developed as a sedative. However, thalidomide induces multiple birth defects when used in pregnant women. Thalidomide is now used in the treatment of multiple myeloma (MM) and erythema nodosum leprosum (ENL) in Japan. Rational use of thalidomide is problematic due to a lack of basic research regarding its mechanism of action and serum concentration/effect relationships. There are a number of hypotheses for pharmacokinetic changes in thalidomide therapy. Genetic factors including single nucleotide polymorphisms (SNPs) that change cytochrome P450 (CYP) activity and epigenetic regulation that modifies CYP expression levels may contribute to the changes in pharmacokinetics and adverse drug reactions (ADRs) of thalidomide. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver and kidney diseases do not play important roles in pharmacokinetic changes or ADRs in thalidomide therapy. To date, most research has focused on teratogenic activity, while the impact of polymorphisms in genes encoding drug metabolic enzymes and drug-drug interactions could mediate ADRs. Here, we discuss clinical evidence of pharmacokinetic changes in thalidomide therapy.

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

    PubMed

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

    2014-03-15

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

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

    PubMed

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

    2014-03-15

    Intensification of agriculture has resulted in increased soil degradation and erosion, with associated pollution of surface waters. Small field wetlands, constructed along runoff pathways, offer one option for slowing down and storing runoff in order to allow more time for sedimentation and for nutrients to be taken up by plants or micro-organisms. This paper describes research to provide quantitative evidence for the effectiveness of small field wetlands in the UK landscape. Ten wetlands were built on four farms in Cumbria and Leicestershire, UK. Annual surveys of sediment and nutrient accumulation in 2010, 2011 and 2012 indicated that most sediment was trapped at a sandy site (70 tonnes over 3 years), compared to a silty site (40 tonnes over 3 years) and a clay site (2 tonnes over 3 years). The timing of rainfall was more important than total annual rainfall for sediment accumulation, with most sediment transported in a few intense rainfall events, especially when these coincided with bare soil or poor crop cover. Nutrient concentration within sediments was inversely related to median particle size, but the total mass of nutrients trapped was dependent on the total mass of sediment trapped. Ratios of nutrient elements in the wetland sediments were consistent between sites, despite different catchment characteristics across the individual wetlands. The nutrient value of sediment collected from the wetlands was similar to that of soil in the surrounding fields; dredged sediment was considered to have value as soil replacement but not as fertiliser. Overall, small field wetlands can make a valuable contribution to keeping soil out of rivers. PMID:24509365

  16. Mononuclear phagocyte accumulation in visceral tissue in HIV encephalitis: evidence for increased monocyte/macrophage trafficking and altered differentiation.

    PubMed

    Fischer, Tracy; Wyatt, Christina M; D'Agati, Vivette D; Croul, Sidney; McCourt, Laura; Morgello, Susan; Rappaport, Jay

    2014-01-01

    The invasion of circulating monocytes/macrophages (MΦ)s from the peripheral blood into the central nervous system (CNS) appears to play an important role in the pathogenesis of HIV dementia (HIV-D), the most severe form of HIV-associated neurocognitive disorders (HAND), often confirmed histologically as HIV encephalitis (HIVE). In order to determine if trafficking of monocytes/MΦs is exclusive to the CNS or if it also occurs in organs outside of the brain, we have focused our investigation on visceral tissues of patients with HIVE. Liver, lymph node, spleen, and kidney autopsy tissues from the same HIVE cases investigated in earlier studies were examined by immunohistochemistry for the presence of CD14, CD16, CD68, Ki-67, and HIV-1 p24 expression. Here, we report a statistically significant increase in accumulation of MΦs in kidney, spleen, and lymph node tissues in specimens from patients with HIVE. In liver, we did not observe a significant increase in parenchymal macrophage accumulation, although perivascular macrophage accumulation was consistently observed with nodular lesions in 4 of 5 HIVE cases. We also observed an absence of CD14 expression on splenic MΦs in HIVE cases, which may implicate the spleen as a potential source of increased plasma soluble CD14 in HIV infection. HIV-1 p24 expression was observed in liver, lymph node and spleen but not kidney. Interestingly, renal pathology suggestive of chronic tubulointerstitial nephritis (possibly due to chronic pyelonephritis), including tubulointerstitial scarring, chronic interstitial inflammation and focal global glomerulosclerosis, without evidence of HIV-associated nephropathy (HIVAN), was seen in four of eight HIVE cases. Focal segmental and global glomerulosclerosis with tubular dilatation and prominent interstitial inflammation, consistent with HIVAN, was observed in two of the eight cases. Abundant cells expressing monocyte/MΦ cell surface markers, CD14 and CD68, were also CD16(+) and found

  17. A review on reporting guidelines of clinical research in evidence based medicine.

    PubMed

    Liao, Xing; Wang, Gui-qian; Xie, Yan-ming

    2015-07-01

    Good clinical practice should be based on evidence. Evidence quality should be based on critical appraisal in evidence based medicine (EBM). Evaluation of evidence quality plays an important role in evidence level clarifying, which is the core of EBM. Different recommendations for clinical practice often derive from evidence levels. Thus evidence quality evaluation is the first and most important step in EBM. There are lots of standards to evaluate evidence quality in the world. However there are two aspects of the evaluation, one is methodological evaluation and the other is reporting evaluation. This article collected a series of standards for clinical trials quality evaluation according to different research designs. It is hoped that the resource and introduction about the quality evaluation of clinical trials be helpful for medical researchers in China. Only being familiar with all kinds of standards of methodology and reporting, researchers could publish high quality scientific papers.

  18. 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.

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

    PubMed Central

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

    2010-01-01

    Summary This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine. PMID:20436026

  20. The Physics of Decision Making:. Stochastic Differential Equations as Models for Neural Dynamics and Evidence Accumulation in Cortical Circuits

    NASA Astrophysics Data System (ADS)

    Holmes, Philip; Eckhoff, Philip; Wong-Lin, K. F.; Bogacz, Rafal; Zacksenhouse, Miriam; Cohen, Jonathan D.

    2010-03-01

    We describe how drift-diffusion (DD) processes - systems familiar in physics - can be used to model evidence accumulation and decision-making in two-alternative, forced choice tasks. We sketch the derivation of these stochastic differential equations from biophysically-detailed models of spiking neurons. DD processes are also continuum limits of the sequential probability ratio test and are therefore optimal in the sense that they deliver decisions of specified accuracy in the shortest possible time. This leaves open the critical balance of accuracy and speed. Using the DD model, we derive a speed-accuracy tradeoff that optimizes reward rate for a simple perceptual decision task, compare human performance with this benchmark, and discuss possible reasons for prevalent sub-optimality, focussing on the question of uncertain estimates of key parameters. We present an alternative theory of robust decisions that allows for uncertainty, and show that its predictions provide better fits to experimental data than a more prevalent account that emphasises a commitment to accuracy. The article illustrates how mathematical models can illuminate the neural basis of cognitive processes.

  1. 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

  2. [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.

  3. [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

  4. Gene medicine for cancer treatment: Commercially available medicine and accumulated clinical data in China

    PubMed Central

    Ma, Guangyu; Shimada, Hideaki; Hiroshima, Kenzo; Tada, Yuji; Suzuki, Nobuo; Tagawa, Masatoshi

    2008-01-01

    Loss of p53 function compromises genetic homeostasis, which induces deregulated DNA replication, damages DNA, and subsequently results in increased resistance to anticancer agents. Pharmacological approaches using recombinant adenoviruses (Ad) have been developed to restore the p53 functions. Another approach for gene medicine is to modify Ad replication in a tumor-specific manner, which induces tumor cell death without damaging normal tissues in the vicinity. The Ad-derived gene medicines, Ad expressing the wild-type p53 gene and replication-competent Ad defective of the E1B-55kDa gene, have been tested for their clinical feasibility and became commercially available in China. These agents demonstrated their antitumor activities as a monotherapy and in combination with conventional chemotherapeutic agents. In this article, we summarize the outcomes of clinical trials in China, most of which have been published in domestic Chinese journals, and discuss potential directions of cancer gene therapy with these agents. PMID:19920899

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

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

    PubMed Central

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

    2015-01-01

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

  13. 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

  14. [PCSK9 inhibitors and dyslipidemias: an update on clinical evidence].

    PubMed

    Norata, Giuseppe Danilo

    2014-05-01

    Elevated plasma LDL cholesterol (LDL-C) levels are associated with cardiovascular diseases and statin therapy was proven to decrease LDL-C and reduce cardiovascular death. However, in patients at high cardiovascular risk, achievement of optimal LDL-C levels is challenging, and therefore additional strategies for further loweing LDL-C levels are under development. Recently, silencing of apolipoprotein B gene and MTP inhibition have been approved for the treatment of patients with familial hypercholesterolemia, and there is great interest in the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9). PCSK9 promotes the degradation of the LDL receptor. The inhibition of PCSK9 favors LDL catabolism and reduces plasma LDLC levels. Monoclonal antibodies against PCSK9 represent so far the most advanced approach in clinical development, with alirocumab, evolocumab and bococizumab under advanced clinical development. Recent data from the first phase III studies show LDL-C reduction in monotherapy and on top of statins. Long-term studies on cardiovascular endpoints are ongoing and the results will be crucial to translate the benefit of this promising approach into clinical practice. PMID:25002170

  15. [PCSK9 inhibitors and dyslipidemias: an update on clinical evidence].

    PubMed

    Norata, Giuseppe Danilo

    2014-05-01

    Elevated plasma LDL cholesterol (LDL-C) levels are associated with cardiovascular diseases and statin therapy was proven to decrease LDL-C and reduce cardiovascular death. However, in patients at high cardiovascular risk, achievement of optimal LDL-C levels is challenging, and therefore additional strategies for further loweing LDL-C levels are under development. Recently, silencing of apolipoprotein B gene and MTP inhibition have been approved for the treatment of patients with familial hypercholesterolemia, and there is great interest in the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9). PCSK9 promotes the degradation of the LDL receptor. The inhibition of PCSK9 favors LDL catabolism and reduces plasma LDLC levels. Monoclonal antibodies against PCSK9 represent so far the most advanced approach in clinical development, with alirocumab, evolocumab and bococizumab under advanced clinical development. Recent data from the first phase III studies show LDL-C reduction in monotherapy and on top of statins. Long-term studies on cardiovascular endpoints are ongoing and the results will be crucial to translate the benefit of this promising approach into clinical practice.

  16. Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.

    PubMed

    Passie, Torsten; Emrich, Hinderk M; Karst, Matthias; Brandt, Simon D; Halpern, John H

    2012-01-01

    It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD. This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories. The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress. Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.

  17. 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

  18. 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

  19. Lipid Peroxidation in Psychiatric Illness: Overview of Clinical Evidence

    PubMed Central

    Joshi, Yash B.; Praticò, Domenico

    2014-01-01

    The brain is known to be sensitive to oxidative stress and lipid peroxidation. While lipid peroxidation has been shown to contribute to many disease processes, its role in psychiatric illness has not been investigated until recently. In this paper, we provide an overview of lipid peroxidation in the central nervous system as well as clinical data supporting a link between lipid peroxidation and disorders such as schizophrenia, bipolar disorder, and major depressive disorder. These data support further investigation of lipid peroxidation in the effort to uncover therapeutic targets and biomarkers of psychiatric disease. PMID:24868318

  20. [Evidence-based medicine and real world study in clinical study of acupuncture and moxibustion].

    PubMed

    Cai, Ronglin; Hu, Ling; Wu, Zijian

    2015-09-01

    Evidence-based medicine (EBM) has been widely applied in clinical study of acupuncture and moxibustion, and the real-world study (RWS) has gradually become an important way of clinical research in the world in recent years. It is worthy of our in-depth study and discussion that how to evaluate the advantages and limitations of EBM and RWS as well as their reasonable application in clinical study of acupuncture and moxibustion. The characteristics and difference between RWS and EBM, and the situation of acupuncture clinical research methods are discussed in this paper. It is proposed that we should understand the advantages of RWS in acupuncture clinical research, fully realize the limitations of EBM and RWS, recognize the complexity and particularity of RWS, and apply EBM and RWS into acupuncture clinical research. Meanwhile acupuncture clinical manipulation standardization should be further promoted, which is benefit to develop clinical study, improve clinical efficacy and promote the popularization of acupuncture and moxibustion.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Cardiac computed tomography--evidence, limitations and clinical application.

    PubMed

    Hamilton-Craig, Christian R; Friedman, Daniel; Achenbach, Stephan

    2012-02-01

    Coronary CT angiography and coronary calcium scoring offer a new approach to the diagnosis of coronary artery disease (CAD). They hold significant promise in improving patient outcomes, through identification of atherosclerosis and improved risk assessment. Coronary calcium scoring has proven predictive value concerning the occurrence of future cardiovascular events and outperforms current risk evaluation methods such as the Framingham Risk Score. Coronary CT angiography allows visualisation of the coronary artery lumen, detection of stenoses as well as visualisation of both calcified and non-calcified plaque. The accuracy of coronary CT angiography to detect obstructive coronary artery disease has been established by numerous trials. In particular the negative predictive value of the test approaches 100% in low and intermediate risk groups. Outcomes data demonstrate significant prognostic ability of coronary CT angiography. Modern techniques allow substantial reduction of dose values and radiation exposure of coronary CT angiography has significantly fallen. Coronary CT angiography can be reliably performed with doses similar to the level of annual background radiation, and less than one-third of a Tc Sestamibi scan. Coronary CT angiography has been approved for Medicare reimbursement for specific indications when performed by accredited providers. High quality examinations, experience and careful patient selection and preparation are required to ensure optimal results of coronary CT angiography, and to guide clinical decisions. PMID:22024629

  14. 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

  15. 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

  16. Cardiovascular diseases and other evidence for primary care clinical practice.

    PubMed

    Bowman, Marjorie A; Neale, Anne Victoria

    2012-01-01

    This issue includes several articles about various cardiovascular illnesses.(1-4) and another on a disease with increased risk for heart disease: hereditary hemochromatosis.(5) Yet another explores some myth busting about mortality and diabetes.(6) Two articles provide data with the support of patient and/or family organizations (Parent Heart Watch(1) and the Iron Disorders Institute(5)). Another 2 articles address maternal-child health, one considers treatment of hyperbilirubinemia,(7) and one describes an innovative team structure for pre-, post-, and intrapartum care.(8) We also provide preliminary data on azithromycin for chronic obstructive pulmonary disease. Pop quiz: What is the common contaminant with cocaine that causes serious side effects? What are these side effects? And another: What nonliver disease should be considered for children with elevated transaminase levels? (See the brief reports for answers.) Two reviews provide up-to-the minute practical facts for vaccinations and treatment-resistant hypertension that can be immediately incorporated into clinical practice. We also have an update on physician perspectives after 2 years of electronic medical record use and another with insights about the satisfaction of family physicians who are working in health centers in the first few years out of their residency. PMID:22773706

  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. 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

  19. [Problems and strategies in developing Chinese medicine evidence-based clinical practice guidelines].

    PubMed

    Wang, Bo; Zhan, Si-yan; Liu, Bao-yan

    2011-11-01

    Some problems are confronted in the development of Chinese medicine (CM) evidence-based clinical practice guidelines in the aspects of individualized treatment, quality of research, reporting bias, safety assessment, and so on. After comprehensive retrieving of current methods for developing evidence-based clinical practice guidelines in the field of complementary and alternative medicine, and an optimal combining with widely accepted standardized methods in evidence-based clinical practice guidelines for allopathic medicine, we put forward strategies for these aforesaid problems. In terms of individualized treatment, practical randomized control trials could be considered for inclusion. In terms of quality of research, the method to formulate guideline recommendations was proposed in case of insufficient evidence. In terms of reporting bias, commonly used databases in complementary and alternative medicine were listed. In terms of safety evaluation, GRADE system was suggested to adopt.

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

    PubMed Central

    Gray, Shelly L.; Hanlon, Joseph T.

    2016-01-01

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

  1. 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) ...

  2. 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.

  3. 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.

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

    PubMed

    Oja, Kenneth J

    2011-03-01

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

  5. 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

  6. Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging.

    PubMed Central

    Pallotti, F.; Chen, X.; Bonilla, E.; Schon, E. A.

    1996-01-01

    It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations in two small regions of the human mitochondrial genome. We observed low levels of somatic mutations above background in both regions, but there was no correlation between the amount of mutation detected and the age of the subject. These results contrasted with our finding of an age-related increase in the amount of the mtDNA "common deletion" in these very samples. Thus, it appears that both somatic mtDNA point mutations and mtDNA deletions can arise at low frequency in normal individuals but that, unlike deletions, there is no preferential amplification or accumulation of specific point mutations in skeletal muscle over the course of the normal human life span. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8751860

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

    PubMed

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

    2014-09-01

    Bioaccumulation of microcystins (MC) in zooplankton has been shown in several studies, mainly in field samples. A few studies, however, have demonstrated MC bioaccumulation in laboratory experiments. Although ingestion of cell-bound MC is considered the main route of MC accumulation, another important source is the MC from the dissolved fraction (DMC). This study reports the accumulation of DMC from aqueous extracts of natural bloom samples in three cladoceran species: Moina micrura, Daphnia laevis and Daphnia similis. Animals were exposed for 96 h to aqueous extracts of lyophilized matter from two bloom samples from Colombian reservoirs in different concentrations (25-1000 mg DW L(-1)). Analysis by HPLC-MS detected MC-LR in these samples at concentrations of 434-538 μg g(-1). For the analysis of MC in animal tissues the samples were homogenized and sonicated in methanol:water (75%) and analyzed by ELISA. Results showed that the animals uptake of MC increased with increasing exposure concentrations of aqueous extracts, with M. micrura and D. laevis clones presenting the highest MC concentrations in their tissues (up to 1170-1260 μg g(-1)) while D. similis the lowest (184 μg g(-1)). This study shows, for the first time, that MC uptake from dissolved fraction by zooplankton is possible, not only from the ingestion of seston or cell-bound MC as previously demonstrated. PMID:24880137

  8. 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

  9. 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

  10. 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

  11. The nature of medical evidence and its inherent uncertainty for the clinical consultation: qualitative study

    PubMed Central

    Griffiths, Frances; Green, Eileen; Tsouroufli, Maria

    2005-01-01

    Objective To describe how clinicians deal with the uncertainty inherent in medical evidence in clinical consultations. Design Qualitative study. Setting Clinical consultations related to hormone replacement therapy, bone densitometry, and breast screening in seven general practices and three secondary care clinics in the UK NHS. Participants Women aged 45-64. Results 45 of the 109 relevant consultations included sufficient discussion for analysis. The consultations could be categorised into three groups: focus on certainty for now and this test, with slippage into general reassurance; a coherent account of the medical evidence for risks and benefits, but blurring of the uncertainty inherent in the evidence and giving an impression of certainty; and acknowledging the inherent uncertainty of the medical evidence and negotiating a provisional decision. Conclusion Strategies health professionals use to cope with the uncertainty inherent in medical evidence in clinical consultations include the use of provisional decisions that allow for changing priorities and circumstances over time, to avoid slippage into general reassurance from a particular test result, and to avoid the creation of a myth of certainty. PMID:15684026

  12. [Insist on the nature of evidence-based medicine for the development of glaucoma clinical trial].

    PubMed

    Ge, Jian

    2015-02-01

    Evidence-based medicine (EBM) has markedly promoted the development of ophthalmology.Glaucoma clinical trials have been developed rapidly. Clinical trial papers have been tremendously increasing in the decade, but unhealthy tendency deviating from the nature of EBM---"conscientious, explicit and judicious" has come into notice by the medical society. It is the time to develop patient based medicine, combining with experience-based, experiment-based, ethics-based, economy-based medicine. Only face up to the fundamental problems can we avoid misleading clinicians and provide better health care of affordable, accessible, accountable medical service for patients. This is the intrinsic value of evidence-based medicine.

  13. Clinical trials, case studies, and oral care R&D: inclusivity, consistency, and other atypical evidence.

    PubMed

    Gerlach, Robert W

    2010-03-01

    Evidence-based assessment plays an obvious, growing, and critical role in directly informing clinical decisions in dentistry. The inputs are complex from diverse sources, and outcomes can appreciably influence the research and development process. Emerging trends may indicate the need for assessment of even more complex data. As exemplified by whitening strips development, inclusive, consistent, and atypical evidence may be considered for informed decision making. In addition to the direct applications, such assessment may indirectly support decision making by professional associations, government authorities, and other health care organizations that influence clinical practice behaviors.

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

    PubMed Central

    Sprague, Sheila; Smith, Chris; Bhandari, Mohit

    2015-01-01

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

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

    PubMed

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

    2012-12-01

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

  16. 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

  17. 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.

  18. 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

  19. Evidence-based medicine and clinical fluorodeoxyglucose PET/MRI in oncology.

    PubMed

    Miles, Kenneth; McQueen, Liam; Ngai, Stanley; Law, Phillip

    2015-11-17

    Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) is a hybrid of two technologies each with its own evidence for clinical effectiveness. This article amalgamates evidence for clinical effectiveness of fluorodeoxyglucose (FDG) PET/CT and MRI as separate modalities with current evidence for hybrid PET/MRI and considers whether such an approach might provide a stronger case for the clinical use of PET/MRI at an earlier stage.Because links between diagnostic accuracy and health outcomes have already been established for FDG-PET/CT in the investigation of suspected residual or recurrent malignancies, evidence showing improved diagnostic performance and therapeutic impact from the use of PET/MRI as an alternative would imply clinical effectiveness of this modality for this application. A meta-analysis of studies comparing FDG-PET/CT to MRI in patients with suspected residual disease or recurrence of tumours indicates complementary roles for these modalities. PET demonstrates greater sensitivity for recurrence within lymph nodes whereas MRI is more effective that PET/CT in the detection of skeletal and hepatic recurrence. A review of studies assessing therapeutic impact of PET/MRI suggests a greater likelihood for change in clinical management when PET/MRI is used for assessment of suspected residual or recurrent disease rather than tumour staging.Supplementing the evidence-base for FDG-PET/MRI with studies that compare the components of this hybrid technology deployed separately indicates that FDG-PET/MRI is likely to be clinical effective for the investigation of patients with a range of suspected residual or recurrent cancers. This indication should therefore be prioritised for further health technology assessment.

  20. 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

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

    PubMed

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

    2011-10-01

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

  2. 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.

  3. An extraordinary accumulation of (-)-pinoresinol in cell-free extracts of Forsythia intermedia: evidence for enantiospecific reduction of (+)-pinoresinol.

    PubMed

    Katayama, T; Davin, L B; Lewis, N G

    1992-11-01

    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 catalyse 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 > 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 synthesis [correction of 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. Direct effects of DPP-4 inhibition on the vasculature. Reconciling basic evidence with lack of clinical evidence.

    PubMed

    Fadini, Gian Paolo; Albiero, Mattia; Avogaro, Angelo

    2015-10-01

    Diabetes is burdened by macrovascular and microvascular complications that collectively reduce life expectancy. As the ultimate goal of diabetes treatment is to prevent excess morbidity and mortality associated with its complications, the interest on cardiovascular effects of glucose lowering medications is high. Dipeptidyl peptidase-4 inhibitors (DPP-4i) lower blood glucose by protecting the incretin hormone glucagon-like peptide-1 (GLP-1) from enzymatic degradation, thereby restoring meal-stimulated insulin release. DPP-4 has several non-incretin substrates, including cytokines, chemokines, and neurohormones, which can exert favourable, but also unpredictable, vascular effects, once they are stabilized by DPP-4i. Choi et al. now provide additional evidence that DPP-4i counteracts vascular smooth muscle cell proliferation and migration, resulting in an attenuation of neointimal hyperplasia. Though several other in vitro, preclinical, and preliminary clinical studies on surrogate end-points suggest that DPP-4i can exert similar direct vasculoprotective actions, results of placebo-controlled phase IV trials have so far shown no reduction cardiovascular endpoints by DPP-4i. In this commentary, we put DPP-4 pleiotropy and complexity into context, trying to reconcile why results from basic science have not yet translated into clinical evidence of cardiovascular protection.

  5. Evidence-based practice: how to perform and use systematic reviews for clinical decision-making.

    PubMed

    Kranke, Peter

    2010-09-01

    One approach to clinical decision-making requires the integration of the best available research evidence with individual clinical expertise and patient values, and is known as evidence-based medicine (EBM). In clinical decision-making with the current best evidence, systematic reviews have an important role. This review article covers the basic principles of systematic reviews and meta-analyses, and their role in the process of evidence-based decision-making. The problems associated with traditional narrative reviews are discussed, as well as the way systematic reviews limit bias associated with the assembly, critical appraisal and synthesis of studies addressing specific clinical questions. The relevant steps in writing a systematic review from the formulation of an initial research question to sensitivity analyses in conjunction with the combined analysis of the pooled data are described. Important issues that need to be considered when appraising a systematic review or meta-analysis are outlined. Some of the terms that are used in the reporting of systematic reviews and meta-analyses, such as relative risk, confidence interval, Forest plot or L'Abbé plot, will be introduced and explained. PMID:20523217

  6. 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…

  7. 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)

  8. 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…

  9. 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).…

  10. Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review).

    PubMed

    Grazia, Giulia; Penna, Ilaria; Perotti, Valentina; Anichini, Andrea; Tassi, Elena

    2014-09-01

    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.

  11. Paying more wisely: effects of payment reforms on evidence-based clinical decision-making.

    PubMed

    Lake, Timothy K; Rich, Eugene C; Valenzano, Christal Stone; Maxfield, Myles M

    2013-05-01

    This article reviews the recent research, policy and conceptual literature on the effects of payment policy reforms on evidence-based clinical decision-making by physicians at the point-of-care. Payment reforms include recalibration of existing fee structures in fee-for-service, pay-for-quality, episode-based bundled payment and global payments. The advantages and disadvantages of these reforms are considered in terms of their effects on the use of evidence in clinical decisions made by physicians and their patients related to the diagnosis, testing, treatment and management of disease. The article concludes with a recommended pathway forward for improving current payment incentives to better support evidence-based decision-making.

  12. 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.

  13. Teaching evidence-based clinical practice to neurology and neurosurgery residents.

    PubMed

    Burneo, J G; Jenkins, M E

    2007-06-01

    The primary objective of education in evidence-based clinical practice (EBCP) is to provide a resident or student with the requisite skills to satisfactorily solve real everyday clinical problems throughout their careers and to translate those solutions into better care for patients. At the University of Western Ontario in London, Canada, there is a well-developed and highly successful evidence-based neurology curriculum primarily aimed at residents. This article summarizes the current context of EBCP postgraduate training in the neurological sciences and a detailed description of its purpose, learning outcomes, required resources, content, teaching strategies, and assessment tools. In this program, we teach the principles of EBCP through the review of pertinent neurological clinical questions. The summary of each topic is recorded on our website in the form of critically appraised topics (CATs) in electronically accessible CAT banks. PMID:17418941

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

    PubMed

    Ross, Joseph S

    2016-09-20

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

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

    PubMed

    Ross, Joseph S

    2016-01-01

    The International Committee of Medical Journal Editors (ICMJE) recently announced a bold step forward to require data generated by interventional clinical trials that are published in its member journals to be responsibly shared with external investigators. The movement toward a clinical research culture that supports data sharing has important implications for the design, conduct, and reporting of systematic reviews and meta-analyses. While data sharing is likely to enhance the science of evidence synthesis, facilitating the identification and inclusion of all relevant research, it will also pose key challenges, such as requiring broader search strategies and more thorough scrutiny of identified research. Furthermore, the adoption of data sharing initiatives by the clinical research community should challenge the community of researchers involved in evidence synthesis to follow suit, including the widespread adoption of systematic review registration, results reporting, and data sharing, to promote transparency and enhance the integrity of the research process. PMID:27649796

  16. 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

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

    PubMed

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

    2009-12-01

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

  18. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan.

    PubMed

    Speakman, John R; Selman, Colin

    2011-04-01

    Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories.

  19. 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

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

    PubMed

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

    2014-03-15

    This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." PMID:24634466

  1. Approved Clinical Instructors' Perspectives on Implementation Strategies in Evidence-Based Practice for Athletic Training Students

    PubMed Central

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

    2011-01-01

    Context: Understanding implementation strategies of Approved Clinical Instructors (ACIs) who use evidence-based practice (EBP) in clinical instruction will help promote the use of EBP in clinical practice. Objective: To examine the perspectives and experiences of ACIs using EBP concepts in undergraduate athletic training education programs to determine the importance of using these concepts in clinical practice, clinical EBP implementation strategies for students, and challenges of implementing EBP into clinical practice while mentoring and teaching their students. Design: Qualitative study. Setting: Telephone interviews. Patients or Other Participants: Sixteen ACIs (11 men, 5 women; experience as a certified athletic trainer = 10 ± 4.7 years, experience as an ACI = 6.8 ± 3.9 years) were interviewed. Data Collection and Analysis: We interviewed each participant by telephone. Interview transcripts were analyzed and coded for common themes and subthemes regarding implementation strategies. Established themes were triangulated through peer review and member checking to verify the data. Results: The ACIs identified EBP implementation as important for validation of the profession, changing paradigm shift, improving patient care, and improving student educational experiences. They promoted 3 methods of implementing EBP concepts with their students: self-discovery, promoting critical thinking, and sharing information. They assisted students with the steps of EBP and often faced challenges in implementation of the first 3 steps of EBP: defining a clinical question, literature searching, and literature appraisal. Finally, ACIs indicated that modeling the behavior of making clinical decisions based on evidence was the best way to encourage students to continue using EBP. Conclusions: Athletic training education program directors should encourage and recommend specific techniques for EBP implementation in the clinical setting. The ACIs believed that role modeling is a

  2. 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.

  3. 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.

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

    PubMed

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

    2015-04-01

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

  5. 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

  6. Rules of evidence for clinical trials: the science of finding the truth?

    PubMed

    Cutter, Gary; Aban, Inmaculada

    2008-01-01

    Clinical research must address the vagaries of human variation in disease presentation, course, and response. The therapeutic relationship between the physician and patient, along with their role expectations and outcome expectations, also clouds the conduct and evaluation of clinical research. Today's milieu of hyper-vigilance in ethics has an impact on subject selection, subject continuance, and ultimately generalizability of results. With multiple stakeholders looking more and more to so-called evidence-based medicine, the quality of trials and their evaluations is growing in importance. This paper is organized along the lines of how we receive the news-a series of short sound bites on cautions important in clinical trials. Educated readers, consumers of trial information, and practitioners, as well as subjects participating in clinical trials, require thoughtful participation. This is often lacking in our sound-bite approach to science and results.

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

    PubMed Central

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

    2016-01-01

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

  8. 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

  9. 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.

  10. 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

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

    PubMed

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

    2009-11-01

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

  12. 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.

  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. Doppler echocardiographic evidence of pulmonary hypertension in dogs: a retrospective clinical investigation.

    PubMed

    Paradies, P; Spagnolo, P P; Amato, M E; Pulpito, D; Sasanelli, M

    2014-03-01

    Pulmonary hypertension (PH) decreases resistance to fatigue and life expectancy. The aim of this study was to correlate some indirect Doppler indices of PH with tricuspid and pulmonary regurgitation criteria and to relate PH on different indices with the severity of clinical signs. Furthermore the pathogenetic mechanisms associated to PH development were discussed. Dogs with Doppler echocardiographic evidence of PH diagnosed by assessment of pulmonary and tricuspid regurgitant jet velocity were selected, their clinical records were reviewed and a clinical score was computed. Seventeen cases of PH were identified. The degree of PH was assessed based on systolic or diastolic pulmonary pressure and the indirect Doppler indices (AT/ET and Tei Index) were calculated; data were statistically evaluated. Indirect Doppler indices were calculated also in a control group of seven healthy dogs. The most common clinical signs were coughing, dyspnea and syncope; the most common condition associated to PH development was the left-sided valvular heart disease. A significant positive correlation was found between Tei Index and both the systolic pressure and the severity of PH while no correlations were found between PH on different indices and clinical score and/or severity of clinical signs. Results of this study suggest that Tei-index could be an useful support not only to reveal PH but also to give information on the severity of PH. The clinical picture in dogs with PH is apparently unpredictable and not strictly correlated with the severity of PH.

  16. 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

  17. Clinical evidence for rapid transmission of Lyme disease following a tickbite.

    PubMed

    Hynote, Eleanor D; Mervine, Phyllis C; Stricker, Raphael B

    2012-02-01

    Lyme disease transmission to humans by Ixodes ticks is thought to require at least 36-48 h of tick attachment. We describe 3 cases in which transmission of Borrelia burgdorferi, the spirochetal agent of Lyme disease, appears to have occurred in less than 24 h based on the degree of tick engorgement, clinical signs of acute infection, and immunologic evidence of acute Lyme disease. Health care providers and individuals exposed to ticks should be aware that transmission of Lyme disease may occur more rapidly than animal models suggest. A diagnosis of Lyme disease should not be ruled out based on a short tick attachment time in a subject with clinical evidence of B. burgdorferi infection.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. The evaluation of an evidence-based clinical answer format for pediatricians

    PubMed Central

    2012-01-01

    Background Clinicians are increasingly using electronic sources of evidence to support clinical decision-making; however, there are multiple demands on clinician time, and summarised and synthesised evidence is needed. Clinical Answers (CA) have been developed to address this need; the CA is a synthesised evidence-based summary that supports point-of-care clinical decision-making. The aim of this paper is to report on a survey used to test and improve the CA format. Methods An online survey was sent to pediatricians via e-mail and posted on a child health clinical standards website. Quantitative data analysis consisted primarily of descriptive statistics; qualitative data analysis consisted of content analysis. Results Eighty-three pediatricians responded to the survey. Most respondents found the CA useful or very useful (93%) and agreed or strongly agreed that the layout was effective and allowed them to quickly locate critical information (82%). Quantitative and qualitative data suggested that respondents thought there should be less detail in the linked figures and tables (p = 0.0002), but overall respondents seemed to think there was an appropriate level of detail in most sections of the CA. Conclusions Based on the quantitative and qualitative survey responses, major and minor modifications to the CA format were implemented, such as removing forest plots, adding links in each addendum to bring the user back to the front page, and adding an 'Implications for practice' section to the CA. Findings suggest that CAs will be a useful tool for pediatricians; thus, the research team has now begun creating CAs to assist busy clinicians in their day-to-day clinical practice by providing high-quality information for decision-making at the point-of-care. PMID:22433873

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

    PubMed

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

    2013-01-01

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

  4. 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%.

  5. [Does evidence-based surgery harm autonomy in clinical decision making?].

    PubMed

    Loss, J; Nagel, E

    2005-02-01

    Evidence-based clinical guidelines in surgery are frequently confronted with scepticism by the medical staff, especially because a confinement of free decision making in therapy is expected. Considering that medicine is not merely natural science, but can as well be comprehended as social science or art, evidence-based medicine (EbM) may lead to an oversimplified and rigid standardization in medical care ("cook book medicine"). In addition, scientific progress might be prevented by inflexible guidelines. However, it is important for surgeons to engage in the development of evidence-based guidelines in order to put forward their interests, because it is the lack of medical guidelines that might threaten free decision making in surgery - by not confronting economical pressure with decisive minimal standards in medical care. Therapeutical freedom is a substantial principle in medicine, but it should be considered that according to occidental tradition, "freedom" is necessarily involving reason and conscientiousness.

  6. 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

  7. 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

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

    PubMed Central

    da Silva, Luiz Vicente Ribeiro Ferreira; Ferreira, Flavia de Aguiar; Reis, Francisco José Caldeira; de Britto, Murilo Carlos Amorim; Levy, Carlos Emilio; Clark, Otavio; Ribeiro, José Dirceu

    2013-01-01

    Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO–an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group. PMID:24068273

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

    PubMed

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

    2011-10-01

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

  10. 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

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

    PubMed

    Hansen, Helena

    2013-12-01

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

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

    PubMed

    Dubois, Robert W; Dean, Bonnie B

    2006-08-01

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

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

    PubMed

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

    2014-03-01

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

  14. Platelet-rich plasma therapy: a systematic literature review and evidence for clinical use.

    PubMed

    Redler, Lauren H; Thompson, Scott A; Hsu, Stephanie H; Ahmad, Christopher S; Levine, William N

    2011-02-01

    Platelet-rich plasma (PRP) is an autologous blood-derived product with an increased concentration of platelets in plasma, which are used to deliver supraphysiological levels of growth factors. Platelet-rich plasma has been used in many fields, including oral, maxillofacial, and plastic surgery. Its use in sports medicine has been increasing after recent evidence and media publicity suggest that it may augment the treatment of muscle strains, as well as tendon and ligament healing. Basic science and animal studies show promising results, but high-level clinical trials have yet to prove its efficacy. With increasing media coverage on the use of PRP in athletes, it is paramount that orthopedic surgeons and sports medicine physicians understand the various methods of preparation and administration, potential clinical applications, and available clinical results to best counsel patients on its advantages and disadvantages. PMID:21378486

  15. 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

  16. Development of evidence-based clinical practice guidelines (CPGs): comparing approaches

    PubMed Central

    Turner, Tari; Misso, Marie; Harris, Claire; Green, Sally

    2008-01-01

    Background While the potential of clinical practice guidelines (CPGs) to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it. Methods CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'. Results Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO). There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting recommendations, consultation with

  17. 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

  18. 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

  19. 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

  20. 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

  1. [Evidence-based medicine. 1. The transfer of research results to clinical practice. The Italian Group for Evidence-Based Medicine-GIMBE].

    PubMed

    Cartabellotta, A

    1998-03-01

    Evidence-based Medicine, born officially in November 1992, during last five years is grown everywhere, showing its power to influence virtually all aspects of health care: clinical practice, medical education, patient information and health policy. Because of the raising interest also in Italy for the new paradigm of clinical practice, "Recently Progress in Medicina" launches a series of articles with the aim of giving to physicians tools and skills for searching, critically appraising and implementing in their own decisions the best results of clinical research. For a better explanation of practical aspects of Evidence-based Medicine, the first article discusses about several obstacles existing in transferring correctly and timely the results of research into clinical practice, and about the potential role of Evidence-based Medicine in the evolution of the medical art and the health systems of the third millennium.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  3. 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

  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

    2006-03-17

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

  6. 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.

  7. 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.

  8. 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

  9. Evidence, research, and clinical practice: a patient-centered framework for progress in wound care.

    PubMed

    van Rijswijk, Lia; Gray, Mikel

    2011-09-01

    Traditional criteria used in selecting wound care interventions are being slowly replaced with an evidence-based practice approach. The value of such an approach for providing optimal care has been established, but the definition of evidence- based care and the process used to generate evidence continue to evolve. For example, the role of studies developed to demonstrate efficacy, randomized controlled trials (RCT), the value of effectiveness studies designed to evaluate outcomes in real world practice, and the use of disease-oriented (interim) study outcomes for wound care research such as reduces wound fluid or improves granulation tissue formation have been topics of international conversations and consensus documents. In addition, the use in some clinical studies and most systematic study reviews of ingredient- or characteristic-based categories to group products that may not share a common operational definition of how they function has led to a high variability in outcomes, resulting in inconclusive or low-level evidence. These concerns and debates, along with their influence on practice, may cast doubt on the value of evidence-based practice guidelines for some clinicians, slowing their rate of implementation and extending the discussion about definitions of evidence-based care and the relative merits of various research designs. At the same time, amid growing concerns about medical device safety, clinicians must answer three questions about an intervention and its related products or devices in order to provide safe and effective care: 1) Can it work? 2) Does it work? 3) Is it worth it? Reviewing current knowledge about wound care, wound treatment modalities, and the basic principles of research within the existing framework of questions to be answered suggests a clear path toward obtaining much-needed evidence. In wound care, using clearly defined process- es to study patient-centered outcomes (eg, quality of life, complete healing) and

  10. Evidence, research, and clinical practice: a patient-centered framework for progress in wound care.

    PubMed

    van Rijswijk, Lia; Gray, Mikel

    2012-01-01

    Traditional criteria used in selecting wound care interventions are being slowly replaced with an evidence-based practice approach. The value of such an approach for providing optimal care has been established, but the definition of evidence-based care and the process used to generate evidence continue to evolve. For example, the role of studies developed to demonstrate efficacy, randomized controlled trials, the value of effectiveness studies designed to evaluate outcomes in real world practice, and the use of disease-oriented (interim) study outcomes for wound care research, such as reduces wound fluid or improves granulation tissue formation, have been topics of international conversations and consensus documents. In addition, the use in some clinical studies and most systematic study reviews of ingredient or characteristic-based categories to group products that may not share a common operational definition of how they function has led to a high variability in outcomes, resulting in inconclusive or low-level evidence. These concerns and debates, along with their influence on practice, may cast doubt on the value of evidence-based practice guidelines for some clinicians, slowing their rate of implementation, and extending the discussion about definitions of evidence-based care and the relative merits of various research designs. At the same time, amid growing concerns about medical device safety, clinicians must answer 3 questions about an intervention and its related products or devices in order to provide safe and effective care: (1) Can it work? (2) Does it work? (3) Is it worth it? Reviewing current knowledge about wound care, wound treatment modalities, and the basic principles of research within the existing framework of questions to be answered suggests a clear path toward obtaining much-needed evidence. In wound care, using clearly defined processes to study patient-centered outcomes (eg, quality of life, complete healing) and only product groupings that

  11. 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

  12. Treatment of urinary tract infection in persons with spinal cord injury: guidelines, evidence, and clinical practice

    PubMed Central

    Pannek, Juergen

    2011-01-01

    Objectives To investigate current clinical practice in the treatment of urinary tract infections (UTIs) in persons with spinal cord injury (SCI) in SCI centers where German is spoken and to compare it with current guidelines and evidence-based standards evaluated by a literature review. Methods A standardized questionnaire was mailed to 16 SCI rehabilitation centers. The results were compared with a literature review Results Of the 16 centers, 13 responded. Indications for UTI treatment, medications, and treatment duration differed substantially among the individual centers and from the existing guidelines. Antibiotic treatment is regarded as the method of choice. Compared with the existing literature, patients in two center were undertreated, whereas they were overtreated in seven centers. Conclusion Even in specialized centers, treatment of UTI in patients with SCI is based more on personal experience of the treating physicians than on published evidence. This may at least partly be due to the paucity of evidence-based data. The observed tendency toward overtreatment with antibiotics carries substantial future risks, as this strategy may well lead to the induction of multiresistant bacterial strains. Therefore, developing guidelines would be an important step toward a unification of the different treatment strategies, thus reducing unnecessary antibiotic treatment. Furthermore, evidence-based studies evaluating the success of antibiotic treatment as well as the usefulness of alternative strategies are urgently needed. PMID:21528621

  13. 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

  14. 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

  15. 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

  16. 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

  17. Clinical decision support and acute low back pain: evidence-based order sets.

    PubMed

    Forseen, Scott E; Corey, Amanda S

    2012-10-01

    Low back pain is one of the most common reasons for visits to physicians in the ambulatory care setting. Estimated medical expenditures related to low back pain have increased disproportionately relative to the more modest increase in the prevalence of self-reported low back pain in the past decade. The increase in spine care expenditures has not been associated with improved patient outcomes. Evidence-based order templates presented in this article are designed to assist practitioners through the process of managing patients with acute low back pain. A logical method of choosing, developing, and implementing clinical decision support interventions is presented that is based on the best available scientific evidence. These templates may be reasonably expected to improve patient care, decrease inappropriate imaging utilization, reduce the inappropriate use of steroids and narcotics, and potentially decrease the number of inappropriate invasive procedures. PMID:23025864

  18. Evidence Base of Clinical Studies on Tai Chi: A Bibliometric Analysis

    PubMed Central

    Yang, Guo-Yan; Zhang, Yan; Li, Meng-Ling; Zhu, Yu-Ting; Luo, Jing; Cheng, Yan-Jun; Li, Wen-Yuan; Wayne, Peter M.; Liu, Jian-Ping

    2015-01-01

    Background The safety and health benefits of Tai Chi mind-body exercise has been documented in a large number of clinical studies focused on specific diseases and health conditions. The objective of this systematic review is to more comprehensively summarize the evidence base of clinical studies of Tai Chi for healthcare. Methods and Findings We searched for all types of clinical studies on Tai chi in PubMed, the Cochrane Library and four major Chinese electronic databases from their inception to July 2013. Data were analyzed using SPSS17.0 software. A total of 507 studies published between 1958 and 2013 were identified, including 43 (8.3%) systematic reviews of clinical studies, 255 (50.3%) randomized clinical trials, 90 (17.8%) non-randomized controlled clinical studies, 115 (22.7%) case series and 4 (0.8%) case reports. The top 10 diseases/conditions was hypertension, diabetes, osteoarthritis, osteoporosis or osteopenia, breast cancer, heart failure, chronic obstructive pulmonary disease, coronary heart disease, schizophrenia, and depression. Many healthy participants practiced Tai Chi for the purpose of health promotion or preservation. Yang style Tai Chi was the most popular, and Tai Chi was frequently practiced two to three 1-hour sessions per week for 12 weeks. Tai Chi was used alone in more than half of the studies (58.6%), while in other studies Tai Chi was applied in combination with other therapies including medications, health education and other physical therapies. The majority of studies (94.1%) reported positive effects of Tai Chi, 5.1% studies reported uncertain effects and 0.8% studies reported negative effects. No serious adverse events related to Tai Chi were reported. Conclusions The quantity and evidence base of clinical studies on Tai Chi is substantial. However, there is a wide variation in Tai Chi intervention studied and the reporting of Tai Chi intervention needs to be improved. Further well-designed and reported studies are recommended to

  19. [Development and Quality Evaluation of Evidence-based Clinical Practice Guidelines of Chinese Medicine].

    PubMed

    Jiang, Yue-rong; Chen, Ke-ji

    2016-01-01

    More attentions have been paid to the development of evidence-based clinical practice guidelines (ECPGs) of Chinese medicine (CM). International guideline evaluation instruments such as Appraisal of Guidelines for Research and Evaluation (AGREE I) has been gradually applied in ECPGs quality evaluation of CM. Nowadays, there are some certain methodological defects in partial ECPGs of Chinese medicine, with relatively low applicability and slowly update. It is suggested to establish technical specifications of CM-ECPGs in accordance with the characteristics of CM and international general specification, strengthen the quality evaluation of CM-ECPGs, attach great importance to the regularly update as well as popularization and application of CM-ECPGs.

  20. 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

  1. Use of biologics in SLE: a review of the evidence from a clinical perspective.

    PubMed

    Aytan, Jayoti; Bukhari, Marwan A S

    2016-05-01

    With the explosion in biologics use in rheumatology, newer and smarter ways of using these drugs in different diseases have been advocated. SLE has to date been at the back of the biologics algorithms. Recently, the US Food and Drug Administration and European Medicines Evaluation Agency licensed belimumab for use in SLE, the first drug in >30 years. A clinical review of the evidence that underlies the use of belimumab and other biologics in SLE reveals possible reasons why the results are not as spectacular as they are in other diseases.

  2. 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

  3. Study on the methodology of developing evidence-based clinical practice guidelines of Chinese medicine.

    PubMed

    Chen, Zheng-guang; Luo, Hui; Xu, Shan; Yang, Yan; Wang, Shou-chuan

    2015-11-01

    At present, evidence-based clinical practice guideline (EBCPG) is the main mode of developing clinical practice guidelines (CPGs) in the world, but in China, most of CPGs of Chinese medicine (CM) are still guidelines based on expert consensus. The objective of this study is to construct initially the methodology of developing EBCPGs of CM and to promote the development of standardization of CM. Based on the development of "Guideline for Diagnosis and Treatment of Common Pediatric Diseases in CM", the methodology of developing EBCPG of CM was explored by analyzing the pertinent literature and considering the characteristics of CM. In this study, the key problem was to put forward the suggestion and strategies. However, due to the methodology study of developing EBCPG of CM is still in the initial stage, there are still some problems which need further study.

  4. 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.

  5. Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence.

    PubMed

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

    2014-11-01

    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: (i) MHC class I expression upregulation; (ii) recruitment and proliferation of effector cells; (iii) upregulation of the lytic activity of cytotoxic effectors; and (iv) 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.

  6. '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

  7. 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

  8. 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

  9. Pragmatic evidence and textual arrangements: a case study of French clinical cancer guidelines.

    PubMed

    Knaapen, Loes; Cazeneuve, Hervé; Cambrosio, Alberto; Castel, Patrick; Fervers, Beatrice

    2010-08-01

    Both critics and supporters of evidence-based medicine view clinical practice guidelines as an important component of this self-defined "new paradigm" whose goal is to rationalize medicine by grounding clinical decision-making in a careful assessment of the medical literature. We present an analysis of the debates within a guideline development group (GDG) that led to the drafting, revision and publication of a French cancer guideline. Our ethnographic approach focuses on the various aspects of the dispositif (or apparatus) that defines the nature and roles of participants, procedures, topics and resources within the GDG. Debates between GDG members are framed (but not dictated) by procedural and methodological rules as well as by the reflexive critical contributions of the GDG members themselves, who justify their (tentative) recommendations by relating to its (possible or intended) audiences. Guideline production work cannot be reduced to an exchange of arguments and to consensus-seeking between pre-defined professional interests. It is about the production of a text in the material sense of the term, i.e. as a set of sentences, paragraphs, statements and formulations that GDG members constantly readjust and rearrange until closure is achieved. As such, guidelines partake in the emergence and stabilization of a new configuration of biomedical knowledge and practices grounded in the establishment of mutually constitutive links between two processes: on the one hand, the re-formatting of clinical trials into a device for producing carefully monitored evidence statements targeting specific populations and clinical indications and, on the other hand, the increasingly pervasive role of regulatory processes. PMID:20646809

  10. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy.

    PubMed

    Strigari, Lidia; Konijnenberg, Mark; Chiesa, Carlo; Bardies, Manuel; Du, Yong; Gleisner, Katarina Sjögreen; Lassmann, Michael; Flux, Glenn

    2014-10-01

    Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in the treatment of an increasing number of cancers. As with other treatment modalities, there is related toxicity to a number of organs at risk. Despite the large number of clinical trials over the past several decades, considerable uncertainties still remain regarding the optimization of this therapeutic approach and one of the vital issues to be answered is whether an absorbed radiation dose-response exists that could be used to guide personalized treatment. There are only limited and sporadic data investigating MRT dosimetry. The determination of dose-effect relationships for MRT has yet to be the explicit aim of a clinical trial. The aim of this article was to collate and discuss the available evidence for an absorbed radiation dose-effect relationships in MRT through a review of published data. Based on a PubMed search, 92 papers were found. Out of 79 studies investigating dosimetry, an absorbed dose-effect correlation was found in 48. The application of radiobiological modelling to clinical data is of increasing importance and the limited published data on absorbed dose-effect relationships based on these models are also reviewed. Based on National Cancer Institute guideline definition, the studies had a moderate or low rate of clinical relevance due to the limited number of studies investigating overall survival and absorbed dose. Nevertheless, the evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.

  11. 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.

  12. 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

  13. 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

  14. Surface passivation by human albumin of plasmapheresis circuits reduces platelet accumulation and thrombus formation. Experimental and clinical studies.

    PubMed

    Mulvihill, J N; Faradji, A; Oberling, F; Cazenave, J P

    1990-02-01

    The contact of flowing blood with an artificial surface leads to adsorption of plasma proteins, followed by platelet adhesion and aggregation and thrombus formation. This phenomenon is enhanced by turbulent flow at joints, bifurcations, and constrictions. In therapeutic plasmapheresis using an IBM blood cell separator, blockage of the extracorporeal circulation system by platelet-fibrin thrombi imposed a halt in treatment for manual clearance of the circuit for 66 in 149 cases (44%). Thus it was decided to passivate the surface of the extracorporeal circuit by filling the tubing with 4% human serum albumin 15-20 min before the treatment session and then displacing the albumin solution with the patient's blood without creating an air-liquid interface. After introduction of this technique, a blockage was observed for only 11 in 239 cases (5%). In vitro measurements of platelet accumulation on the internal surface of the circulation system were carried out using washed human platelets labeled with 111In-oxine in the presence of a 40% hematocrit. Preadsorption of the surface with albumin reduced platelet deposition to 4-5% that observed for an equivalent pretreatment with physiological saline. PMID:2329112

  15. 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

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

    PubMed

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

    2014-10-01

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

  17. 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

  18. 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

  19. 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.

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. [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

  3. 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.

  4. 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

  5. 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…

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

    PubMed Central

    Ud-Din, Sara; Bayat, Ardeshir

    2014-01-01

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

  7. 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

  8. 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

  9. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. 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…

  13. 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…

  14. Treatment of African children with severe malaria - towards evidence-informed clinical practice using GRADE

    PubMed Central

    2011-01-01

    Background Severe malaria is a major contributor of deaths in African children up to five years of age. One valuable tool to support health workers in the management of diseases is clinical practice guidelines (CPGs) developed using robust methods. A critical assessment of the World Health Organization (WHO) and Kenyan paediatric malaria treatment guidelines with quinine was undertaken, with a focus on the quality of the evidence and transparency of the shift from evidence to recommendations. Methods Systematic reviews of the literature were conducted using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to appraise included studies. The findings were used to evaluate the WHO and Kenyan recommendations for the management of severe childhood malaria. Results The WHO 2010 malaria guidance on severe malaria in children, which informed the Kenyan guidelines, only evaluated the evidence on one topic on paediatric care using the GRADE tool. Using the GRADE tool, this work explicitly demonstrated that despite the established use of quinine in the management of paediatric cases of severe malaria for decades, low or very low quality evidence of important outcomes, but not critical outcomes such as mortality, have informed national and international guidance on the paediatric quinine dosing, route of administration and adverse effects. Conclusions Despite the foreseeable shift to artesunate as the primary drug for treatment of severe childhood malaria, the findings reported here reflect that the particulars of quinine therapeutics for the management of severe malaria in African children have historically been a neglected research priority. This work supports the application of the GRADE tool to make transparent recommendations and to inform advocacy efforts for a greater research focus in priority areas in paediatric care in Africa and other low-income settings. PMID:21777441

  15. 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

  16. 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

  17. 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…

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  19. 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

  20. 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

  1. 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

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

    PubMed Central

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

    2016-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Connecting Personality Structure and Dynamics: Towards a More Evidence-Based and Clinically Useful Diagnostic Scheme.

    PubMed

    Hopwood, Christopher J; Zimmermann, Johannes; Pincus, Aaron L; Krueger, Robert F

    2015-08-01

    The purpose of this special issue of the Journal of Personality Disorders is to promote the integration of personality structure and dynamics towards more evidence-based and clinically useful conceptualizations of personality pathology. In this article, we describe a contemporary model of personality structure that is useful for distinguishing patients from one another and the connections between this structure and within-person dynamics that occur across different levels of an individual personality, across situations, and within situations. In so doing, we connect the personality trait tradition that has tended to emphasize stable individual differences with traditions that have tended to focus on the more dynamic aspects of interpersonal behavior and emotional experience. We then introduce the empirical articles in this special issue within this integrative context, in order to demonstrate the value in connecting personality structure to dynamics for research and practice.

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

    PubMed Central

    2012-01-01

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

  12. [The evidence base of clinical practice guidelines, health technology assessments and patient information as a basis for clinical decision-making].

    PubMed

    Antes, Gerd

    2004-05-01

    Valid assessments of benefit and harm of health care interventions are derived from unbiased patient-based clinical trials. Bias sources may affect different study types in different ways, leading to varying validity of study results. The efficient transfer of relevant study results into medical practice is the main objective of evidence-based medicine. To archive this, systematic reviews summarising the study results with respect to a focussed question have proved a powerful tool. They can be used for decision making by individuals as well as evidence source for clinical practice guidelines, health technology assessment and patient information.

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

    PubMed

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

    2007-04-01

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

  14. 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.

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

    PubMed

    Bennell, Kim L; Hinman, Rana S

    2011-01-01

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

  16. Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.

    PubMed

    Kondo-Iida, E; Saito, K; Tanaka, H; Tsuji, S; Ishihara, T; Osawa, M; Fukuyama, Y; Toda, T

    1997-04-01

    Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with brain malformation. The gene responsible for FCMD was mapped to chromosome 9q31, a region in which convincing evidence of strong linkage disequilibrium between FCMD and mfd220 (D9S306) was recently found. FCMD is also characterized clinically by a peak motor function which, at best, allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the capacity to walk unassisted. Whether such ambulant cases belong to the FCMD spectrum or to a different disease entity has been a topic of considerable debate. We performed linkage analysis for ten families with ambulant cases using DNA markers flanking the FCMD locus. The mfd220 locus yielded a significant lod score of 3.09 for ambulant FCMD. We also found evidence for linkage disequilibrium between ambulant FCMD and mfd220. We further conducted haplotype analysis in FCMD siblings with different phenotypes, one of whom was ambulant while the other was not. The results indicate that the FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, we conclude that, genetically, ambulant cases are, in fact, part of the FCMD spectrum.

  17. Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity.

    PubMed

    Rocca, Walter A; Grossardt, Brandon R; Shuster, Lynne T

    2011-03-16

    The neuroprotective effects of estrogen have been demonstrated consistently in cellular and animal studies but the evidence in women remains conflicted. We explored the window of opportunity hypothesis in relation to cognitive aging and dementia. In particular, we reviewed existing literature, reanalyzed some of our data, and combined results graphically. Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age at the time of treatment, type of menopause (natural versus medically or surgically induced), or stage of menopause. The comparison of women who underwent bilateral oophorectomy with referent women provided evidence for a sizeable neuroprotective effect of estrogen before age 50 years. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, recent clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. The current conflicting data can be explained by the window of opportunity hypothesis suggesting that the neuroprotective effects of estrogen depend on age at the time of administration, type of menopause, and stage of menopause. Therefore, women who underwent bilateral oophorectomy before the onset of menopause or women who experienced premature or early natural menopause should be considered for hormonal treatment until approximately age 51 years.

  18. 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

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

    PubMed Central

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

    2015-01-01

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

  20. Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

    PubMed

    Mazzanti, Gabriela; Di Giacomo, Silvia

    2016-09-17

    A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized.

  1. 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.

  2. High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies.

    PubMed

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

    2014-01-01

    High-density lipoprotein (HDL) particles transport (among other molecules) cholesterol (HDL-C). In epidemiological studies, plasma HDL-C levels have an inverse relationship to the risk of atherosclerotic cardiovascular disease. It has been assumed that this reflects the protective functions of HDL, which include their ability to promote cholesterol efflux. Yet, several recent pharmacological and genetic studies have failed to demonstrate that increased plasma levels of HDL-C resulted in decreased cardiovascular disease risk, giving rise to a controversy regarding whether plasma levels of HDL-C reflect HDL function, or that HDL is even as protective as assumed. The evidence from preclinical and (limited) clinical studies shows 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. Although more research will be needed regarding basic mechanisms and to establish that these changes translate clinically to reduced cardiovascular disease events, that HDL can regress plaques suggests that the recent trial failures do not eliminate HDL from consideration as an atheroprotective agent but rather emphasizes the important distinction between HDL function and plasma levels of HDL-C.

  3. Clinical and lay preferences for the explicit prioritisation of elective waiting lists: survey evidence from Wales.

    PubMed

    Edwards, Rhiannon Tudor; Boland, Angela; Wilkinson, Clare; Cohen, David; Williams, John

    2003-03-01

    Waiting lists are a persistent feature of public health care systems. The United Kingdom National Health Service (NHS) is considering priority scoring systems as a means of ensuring that patients are treated according to clinical need rather than maximum waiting time targets. Our objective was to elicit the preferences of those involved in the finance, delivery and receipt of elective health care regarding the clinical and social factors that should and should not determine waiting time. We conducted a postal survey of 750 general practitioners, 500 consultants, 29 health authority commissioners and 1000 members of the general public across Wales. We found both professional and lay support for a more explicit system of rationing access to elective health care by waiting list. The majority of each of the survey groups believe that level of pain, rate of deterioration of disease, level of distress and level of disability should play the most influential role in determining waiting times. They agree that age, ability to pay, cost of treatment, evidence of cost-effectiveness, existence of dependants, and self-inflicted ill health should have little or no influence on patient priority. In conclusion, were the NHS to widen its use of waiting list priority scoring systems, our study suggests that there may be some degree of consensus as to the criteria to be used.

  4. Whole grain intake in relation to body weight: from epidemiological evidence to clinical trials.

    PubMed

    Giacco, R; Della Pepa, G; Luongo, D; Riccardi, G

    2011-12-01

    This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring "per se" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. PMID:22036468

  5. 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

  6. Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

    PubMed

    Mazzanti, Gabriela; Di Giacomo, Silvia

    2016-01-01

    A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized. PMID:27649135

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

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

    PubMed

    Laitinen, Kirsi; Gylling, Helena

    2012-10-22

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

  20. 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

  1. Do Evidence-Based Youth Psychotherapies Outperform Usual Clinical Care? A Multilevel Meta-Analysis

    PubMed Central

    Weisz, John R.; Kuppens, Sofie; Eckshtain, Dikla; Ugueto, Ana M.; Hawley, Kristin M.; Jensen-Doss, Amanda

    2013-01-01

    Context Research across four decades has produced numerous empirically-tested evidence-based psychotherapies (EBPs) for youth psychopathology, developed to improve upon usual clinical interventions. Advocates argue that these should replace usual care; but do the EBPs produce better outcomes than usual care? Objective This question was addressed in a meta-analysis of 52 randomized trials directly comparing EBPs to usual care. Analyses assessed the overall effect of EBPs vs. usual care, and candidate moderators; multilevel analysis was used to address the dependency among effect sizes that is common but typically unaddressed in psychotherapy syntheses. Data Sources The PubMed, PsychINFO, and Dissertation Abstracts International databases were searched for studies from January 1, 1960 – December 31, 2010. Study Selection 507 randomized youth psychotherapy trials were identified. Of these, the 52 studies that compared EBPs to usual care were included in the meta-analysis. Data Extraction Sixteen variables (participant, treatment, and study characteristics) were extracted from each study, and effect sizes were calculated for all EBP versus usual care comparisons. Data Synthesis EBPs outperformed usual care. Mean effect size was 0.29; the probability was 58% that a randomly selected youth receiving an EBP would be better off after treatment than a randomly selected youth receiving usual care. Three variables moderated treatment benefit: Effect sizes decreased for studies conducted outside North America, for studies in which all participants were impaired enough to qualify for diagnoses, and for outcomes reported by people other than the youths and parents in therapy. For certain key groups (e.g., studies using clinically referred samples and diagnosed samples), significant EBP effects were not demonstrated. Conclusions EBPs outperformed usual care, but the EBP advantage was modest and moderated by youth, location, and assessment characteristics. There is room for

  2. 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.

  3. 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

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

    PubMed

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

    2014-01-01

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

  5. 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. 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

  7. 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.

  8. Daclatasvir for the Treatment of Chronic Hepatitis C: A Critique of the Clinical and Economic Evidence.

    PubMed

    Llewellyn, Alexis; Faria, Rita; Woods, Beth; Simmonds, Mark; Lomas, James; Woolacott, Nerys; Griffin, Susan

    2016-10-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of daclatasvir (Bristol-Myers Squibb) to submit clinical and cost-effectiveness evidence for daclatasvir in combination with other medicinal products within its licensed indication for the treatment of chronic hepatitis C, as part of the Institute's single technology appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents the ERG's critical review of the evidence presented in the company submission in the context of a description of the company submission, and the resulting NICE guidance. The main clinical effectiveness data for daclatasvir in combination with sofosbuvir (daclatasvir + sofosbuvir) were derived from two uncontrolled open-label trials. Among patients with genotype 1 infection, 98-100 % of patients had a sustained virologic response at week 12 (SVR12), overall. Among genotype 3 patients, between 85 and 100 % had SVR12 across patient populations and regimens. The main evidence for daclatasvir + pegylated interferon-α and ribavirin (PR) came from one randomised controlled trial comparing daclatasvir + PR with PR in patients with genotype 4. This found an SVR12 rate of 82 % in previously untreated patients. Serious adverse event rates associated with daclatasvir were low. The lack of comparative trial evidence for daclatasvir + sofosbuvir and many of the comparators defined in the NICE scope meant that established methods for comparing interventions either directly via head-to-head trial comparisons or via adjusted indirect comparisons were not feasible. Comparisons of SVR rates were therefore largely based on unadjusted estimates drawn from individual trial arms and subgroups of individual trial arms. The ERG concluded that, despite limited evidence, daclatasvir in combination with other treatments

  9. 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

  10. 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.

  11. 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

  12. 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

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

    PubMed

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

    2016-07-01

    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

  14. Evidence-based clinical practice guidelines on the use of sentinel lymph node biopsy in melanoma.

    PubMed

    Sondak, Vernon K; Wong, Sandra L; Gershenwald, Jeffrey E; Thompson, John F

    2013-01-01

    Sentinel lymph node biopsy (SLNB) was introduced in 1992 to allow histopathologic evaluation of the "sentinel" node, that is, the first node along the lymphatic drainage pathway from the primary melanoma. This procedure has less risk of complications than a complete lymphadenectomy, and if the sentinel node is uninvolved by tumor the likelihood a complete lymphadenectomy would find metastatic disease in that nodal basin is very low. SLNB is now widely used worldwide in the staging of melanoma as well as breast and Merkel cell carcinomas. SLNB provides safe, reliable staging for patients with clinically node-negative melanomas 1 mm or greater in thickness, with an acceptably low rate of failure in the sentinel node-negative basin. Evidence-based guidelines jointly produced by ASCO and the Society of Surgical Oncology (SSO) recommend SLNB for patients with intermediate-thickness melanomas and also state that SLNB may be recommended for patients with thick melanomas. Major remaining areas of uncertainty include the indications for SLNB in patients with thin melanomas, pediatric patients, and patients with atypical melanocytic neoplasms; the optimal radiotracers and dyes for lymphatic mapping; and the necessity of complete lymphadenectomy in all sentinel node-positive patients.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2008-01-01

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

  1. 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

  2. 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

  3. 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.

  4. 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…

  5. [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

  6. Graduate Medical Education Training in Clinical Epidemiology, Critical Appraisal, and Evidence-Based Medicine: A Critical Review of Curricula.

    ERIC Educational Resources Information Center

    Green, Michael L.

    1999-01-01

    A study systematically reviewed published literature on graduate medical-education curricula in clinical epidemiology, critical appraisal, and evidence-based medicine (EBM). The 18 reports found in the search provide useful guidelines for medical educators but many suffer from incomplete descriptions and inadequate curriculum evaluations.…

  7. [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.

  8. The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

    PubMed

    Flashner, Yehuda; Fisher, Morly; Tidhar, Avital; Mechaly, Adva; Gur, David; Halperin, Gideon; Zahavy, Eran; Mamroud, Emanuelle; Cohen, Sara

    2010-07-01

    Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease. In a mouse model of pneumonic plague, LcrV can be determined in the bronchoalveolar lavage fluid somewhat later than F1, but before dissemination of Y. pestis to the blood. Thus, determination of soluble LcrV is suggested as a potential useful tool for monitoring disease progression in both bubonic and pneumonic plague. Moreover, it may be of particular advantage in cases of infections with F1 nonproducing strains.

  9. 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.

  10. The importance of physical activity in osteoporosis. From the molecular pathways to the clinical evidence.

    PubMed

    Castrogiovanni, Paola; Trovato, Francesca Maria; Szychlinska, Marta Anna; Nsir, Houda; Imbesi, Rosa; Musumeci, Giuseppe

    2016-11-01

    Osteoporosis is a very common bone disorder characterized by low bone mass and signs of deterioration, responsible for bone fragility typical in this pathology. The risk factors for the onset of osteoporosis are many and different from each other. Some of them cannot be modified, such as age, hereditary diseases and endocrine diseases. Others are modifiable, so that prevention is an advisable tool to reduce the incidence of osteoporosis. Among preventive tools, physical activity is certainly a valid instrument of prevention, in fact physical activity contributes to a healthy energy balance and increases muscle mass and bone mass. In the present narrative review, we wanted to pay attention to the possible influence of physical activity on the pathophysiological molecular pathways of osteoporosis and to the use of different exercise training in treatment of osteoporosis. From the literature analyzed, in relation to the effects of physical activity on bone metabolism, it is shown that exercise acts on molecular pathways of bone remodeling involving all cellular types of bone tissue. In relation to clinical trials adopted in patients with osteoporosis, it is evident that a multi-component training, including aerobic activity and other types of training (resistance and/or strength exercises), is the best kind of exercise in improving bone mass and bone metabolism in older adults and especially osteopoenic and osteoporotic women. With regard to whole-body-vibration training, it seems to be a valid alternative to current methods due to its greater adaptability to patients. In conclusion, physical activity, whatever the adopted training, always has beneficial effects on patients suffering from osteoporosis, and not only on bone homeostasis but on the whole skeletal muscle system.

  11. Cardiovascular autonomic dysfunction in primary ovarian insufficiency: clinical and experimental evidence

    PubMed Central

    Goldmeier, Silvia; De Angelis, Kátia; Rabello Casali, Karina; Vilodre, César; Consolim-Colombo, Fernanda; Belló Klein, Adriane; Plentz, Rodrigo; Spritzer, PoliMara; Irigoyen, Maria-Cláudia

    2014-01-01

    Objective: Women with primary ovarian insufficiency (POI) present an increased risk for cardiovascular disease. In this study we tested the hypothesis that POI in women under hormone therapy (HT) are associated with vascular vasodilatation attenuation and cardiovascular autonomic dysfunction and these impairments are related to changes in systemic antioxidant enzymes. Furthermore, the possibility that ovarian hormone deprivation can induce such changes and that HT cannot reverse all of those impairments was examined in an experimental model of POI. Methods: Fifteen control and 17 patients with primary ovarian insufficiency receiving HT were included in the study. To test the systemic and cardiac consequences of ovarian hormone deprivation, ovariectomy was induced in young female rats that were submitted or not to HT. Spectral analysis of RR interval and blood pressure signals were performed and oxidative stress parameters were determined. Results: POI women under HT have increased mean arterial pressure (94±10 vs. 86±5 mmHg) despite normal endothelial and autonomic modulation of vasculature. Additionally, they presented impaired baroreflex sensitivity (3.9±1.38 vs. 7.15±3.62 ms/mmHg) and reduced heart rate variability (2310±1173 vs. 3754±1921 ms2). Similar results obtained in ovariectomized female rats were accompanied by an increased lipoperoxidation (7433±1010 vs. 6180±289 cps/mg protein) and decreased antioxidant enzymes in cardiac tissue. As it was observed in women, the HT in animals did not restore hemodynamic and autonomic dysfunctions. Conclusion: These data provide clinical and experimental evidence that long term HT may not restore all cardiovascular risk factors associated with ovarian hormone deprivation. PMID:24349626

  12. 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.

  13. New evidence-based adaptive clinical trial methods for optimally integrating predictive biomarkers into oncology clinical development programs

    PubMed Central

    Beckman, Robert A.; Chen, Cong

    2013-01-01

    Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict. PMID:23489587

  14. Heat accumulator

    SciTech Connect

    Bracht, A.

    1981-09-29

    A heat accumulator comprises a thermally-insulated reservoir full of paraffin wax mixture or other flowable or meltable heat storage mass, heat-exchangers immersed in the mass, a heat-trap connected to one of the heat-exchangers, and a heat user connected to the other heat-exchanger. Pumps circulate fluids through the heat-trap and the heat-using means and the respective heat-exchangers, and a stirrer agitates and circulates the mass, and the pumps and the stirrer and electric motors driving these devices are all immersed in the mass.

  15. 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

  16. 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.

  17. 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

  18. Ethnography, fidelity, and the evidence that anthropology adds: supplementing the fidelity process in a clinical trial of supported employment.

    PubMed

    Smith-Morris, Carolyn; Lopez, Gilberto; Ottomanelli, Lisa; Goetz, Lance; Dixon-Lawson, Kimberly

    2014-06-01

    This discussion considers the role and findings of ethnographic research within a clinical trial of supported employment for veterans with spinal cord injury. Contributing to qualitative evaluation research and to debates over anthropological evidence vis-à-vis clinical trials, we demonstrate how enactors of a randomized controlled trial can simultaneously attend to both the trial's evidentiary and procedural requirements and to the lived experiences and needs of patients and clinicians. Three major findings are described: (1) contextual information essential to fidelity efforts within the trial; (2) the role of human interrelationships and idiosyncratic networks in the trial's success; and (3) a mapping of the power and authority structures relevant to the staff's ability to perform the protocol. We emphasize strengths of anthropological ethnography in clinical trials that include the provision of complementary, qualitative data, the capture of otherwise unmeasured parts of the trial, and the realization of important information for the translation of the clinical findings into new settings.

  19. 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

  20. 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

  1. Neurochemical evidence that the metabolites accumulating in 3-methylcrotonyl-CoA carboxylase deficiency induce oxidative damage in cerebral cortex of young rats.

    PubMed

    Zanatta, Ângela; Moura, Alana Pimentel; Tonin, Anelise Miotti; Knebel, Lisiane Aurélio; Grings, Mateus; Lobato, Vannessa Araújo; Ribeiro, César Augusto João; Dutra-Filho, Carlos Severo; Leipnitz, Guilhian; Wajner, Moacir

    2013-01-01

    Isolated 3-methylcrotonyl-CoA carboxylase deficiency (3MCCD) is an autosomal recessive disorder of leucine metabolism biochemically characterized by accumulation of 3-methylcrotonylglycine (3MCG), 3-methylcrotonic acid (3MCA) and 3-hydroxyisovaleric acid. A considerable number of affected individuals present neurological symptoms with or without precedent crises of metabolic decompensation and brain abnormalities whose pathogenesis is poorly known. We investigated the in vitro effects of 3MCG and 3MCA on important parameters of oxidative stress in cerebral cortex of young rats. 3MCG and 3MCA significantly increased TBA-RS and carbonyl formation, indicating that these compounds provoke lipid and protein oxidation, respectively. In contrast, nitric oxide production was not affected by 3MCG and 3MCA. Furthermore, 3MCG- and 3MCA-induced elevation of TBA-RS values was fully prevented by melatonin, trolox and reduced glutathione, but not by the nitric oxide inhibitor N(ω)-nitro-L-arginine methyl ester or the combination of catalase plus superoxide dismutase, indicating that reactive oxygen species were involved in the oxidative damage caused by these compounds. We also found that the activity of the antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase and glutathione reductase were not altered in vitro by 3MCG and 3MCA. It is therefore presumed that alterations of the cellular redox homeostasis caused by the major metabolites accumulating in 3MCCD may potentially be involved in the pathophysiology of the neurological dysfunction and structural brain alterations found in patients affected by this disorder.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

  4. 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

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

    PubMed

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

    2015-04-01

    Clinical decision support systems (CDSSs) assist clinicians with patient diagnosis and treatment. However, inadequate attention has been paid to the process of selecting and buying systems. The diversity of CDSSs, coupled with research obstacles, marketplace limitations, and legal impediments, has thwarted comparative outcome studies and reduced the availability of reliable information and advice for purchasers. We review these limitations and recommend several comparative studies, which were conducted in phases; studies conducted in phases and focused on limited outcomes of safety, efficacy, and implementation in varied clinical settings. Additionally, we recommend the increased availability of guidance tools to assist purchasers with evidence-based purchases. Transparency is necessary in purchasers' reporting of system defects and vendors' disclosure of marketing conflicts of interest to support methodologically sound studies. Taken together, these measures can foster the evolution of evidence-based tools that, in turn, will enable and empower system purchasers to make wise choices and improve the care of patients. PMID:25665704

  6. 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

  7. Using evidence-based algorithms to improve clinical decision making: the case of a first-time anterior shoulder dislocation.

    PubMed

    Federer, Andrew E; Taylor, Dean C; Mather, Richard C

    2013-09-01

    Decision making in health care has evolved substantially over the last century. Up until the late 1970s, medical decision making was predominantly intuitive and anecdotal. It was based on trial and error and involved high levels of problem solving. The 1980s gave way to empirical medicine, which was evidence based probabilistic, and involved pattern recognition and less problem solving. Although this represented a major advance in the quality of medical decision making, limitations existed. The advantages of the gold standard of the randomized controlled clinical trial (RCT) are well-known and this technique is irreplaceable in its ability to answer critical clinical questions. However, the RCT does have drawbacks. RCTs are expensive and can only capture a snapshot in time. As treatments change and new technologies emerge, new expensive clinical trials must be undertaken to reevaluate them. Furthermore, in order to best evaluate a single intervention, other factors must be controlled. In addition, the study population may not match that of another organization or provider. Although evidence-based medicine has provided powerful data for clinicians, effectively and efficiently tailoring it to the individual has not yet evolved. We are now in a period of transition from this evidence-based era to one dominated by the personalization and customization of care. It will be fueled by policy decisions to shift financial responsibility to the patient, creating a powerful and sophisticated consumer, unlike any patient we have known before. The challenge will be to apply medical evidence and personal preferences to medical decisions and deliver it efficiently in the increasingly busy clinical setting. In this article, we provide a robust review of the concepts of customized care and some of techniques to deliver it. We will illustrate this through a personalized decision model for the treatment decision after a first-time anterior shoulder dislocation.

  8. Using evidence-based algorithms to improve clinical decision making: the case of a first-time anterior shoulder dislocation.

    PubMed

    Federer, Andrew E; Taylor, Dean C; Mather, Richard C

    2013-09-01

    Decision making in health care has evolved substantially over the last century. Up until the late 1970s, medical decision making was predominantly intuitive and anecdotal. It was based on trial and error and involved high levels of problem solving. The 1980s gave way to empirical medicine, which was evidence based probabilistic, and involved pattern recognition and less problem solving. Although this represented a major advance in the quality of medical decision making, limitations existed. The advantages of the gold standard of the randomized controlled clinical trial (RCT) are well-known and this technique is irreplaceable in its ability to answer critical clinical questions. However, the RCT does have drawbacks. RCTs are expensive and can only capture a snapshot in time. As treatments change and new technologies emerge, new expensive clinical trials must be undertaken to reevaluate them. Furthermore, in order to best evaluate a single intervention, other factors must be controlled. In addition, the study population may not match that of another organization or provider. Although evidence-based medicine has provided powerful data for clinicians, effectively and efficiently tailoring it to the individual has not yet evolved. We are now in a period of transition from this evidence-based era to one dominated by the personalization and customization of care. It will be fueled by policy decisions to shift financial responsibility to the patient, creating a powerful and sophisticated consumer, unlike any patient we have known before. The challenge will be to apply medical evidence and personal preferences to medical decisions and deliver it efficiently in the increasingly busy clinical setting. In this article, we provide a robust review of the concepts of customized care and some of techniques to deliver it. We will illustrate this through a personalized decision model for the treatment decision after a first-time anterior shoulder dislocation. PMID:23924748

  9. 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…

  10. Holding and restraining children for clinical procedures within an acute care setting: an ethical consideration of the evidence.

    PubMed

    Bray, Lucy; Snodin, Jill; Carter, Bernie

    2015-06-01

    This critical reflection on the ethical concerns of current practice is underpinned by a systematic synthesis of current evidence focusing on why and how children are held or restrained for clinical procedures within acute care and the experiences of those present when a child is held against their wishes. Empirical evidence from a range of clinical settings internationally demonstrates that frequently children are held for procedures to be completed; younger children and those requiring procedures perceived as urgent are more likely to be held. Parents and health professionals express how holding children for procedures can cause feelings of moral distress expressed as uncertainty, guilt and upset and that this act breaches the trusting and protective relationship established with children. Despite this, children's rights and alternatives to holding are not always respected or explored. Children's experiences and perceptions are absent from current literature. Children and young people have a moral right to have their voice and protests heard and respected and for these to inform judgements of their best interests and the actions of health professionals. Without robust evidence, debate and recognition that children are frequently held against their wishes in clinical practice for procedures which may not be urgent, children's rights will continue to be compromised. PMID:25053126

  11. 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

  12. Clinical evidence of growth hormone, glutamine and a modified diet for short bowel syndrome: meta-analysis of clinical trials.

    PubMed

    Zhou, Yong; Wu, Xiao-Ting; Yang, Gang; Zhuang, Wen; Wei, Mao-ling

    2005-01-01

    This study assessed the safety and efficacy of growth hormone (GH) and glutamine (GLN) combined with a modified (high-carbohydrate-low-fat, HCLF) diet in patients with short bowel syndrome. A meta-analysis of all the relevant clinical trials was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in May 2004. Language was restricted to Chinese and English. Literature references were checked at the same time. Clinical trials were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. Thirteen trials involving 258 patients were included. The combined results showed that GH, GLN and HCLF diet had positive treatment effect on body weight (weighted mean difference [WMD] = 2.44, 95%CI [1.62, 3.27], P<0.00001), stool output (WMD = -376.49, 95%CI [-600.35, -152.63], P=0.001), lean body mass (WMD = 2.16, 95%CI [0.91, 3.41], P=0.0007), absorption of carbohydrates (WMD = 6.21, 95%CI [5.27, 7.15], P< 0.00001), absorption of nitrogen (WMD = 10.83, 95%CI [5.22, 16.44], P=0.0002), absorption of D-xylose (WMD = 0.37, 95%CI [0.29, 0.44], P<0.00001), and off TPN (total parenteral nutrition) (odds ratios [OR] = 64.63, 95%CI [15.51, 269.22], P<0.00001). But there were no improvements in fat mass (WMD = -1.50, 95%CI [-3.48, 0.48], P=0.14), absorption of energy (WMD = 7.48, 95%CI [-7.22, 22.17], P=0.32), and absorption of fat (WMD = 7.16, 95%CI [-2.95, 17.28], P=0.17). Most patients had side effects that are known to occur during treatment with high doses (0.14 mg/kg/day) of GH. No serious adverse effects occurred during active treatment with low doses (< or =0.1 mg/kg/day) of GH. Treatment with a combination of low-dose GH, GLN and HCLF diet is effective

  13. Addiction treatment provider attitudes on staff capacity and evidence-based clinical training: results from a national study.

    PubMed

    Lundgren, Lena; Amodeo, Maryann; Krull, Ivy; Chassler, Deborah; Weidenfeld, Rachel; de Saxe Zerden, Lisa; Gowler, Rebekah; Lederer, Jaime; Cohen, Alexander; Beltrame, Clelia

    2011-01-01

    This national study of addiction-treatment organizations' implementation of evidence-based practices examines: (1) organizational/leadership factors associated with director (n = 212) attitudes regarding staff resistance to organizational change, and (2) organizational/staff factors associated with staff (n = 312) attitudes regarding evidence-based clinical training. Linear regression analyses, controlling for type of treatment unit, leadership/staff characteristics and organizational readiness to change, identified that directors who perceived their organization needed more guidance and had less staff cohesion and autonomy rated staff resistance to organizational change significantly higher. Staff with higher levels of education and greater agreement that their organization supported change had greater preference for evidence-based trainings. Federal addiction treatment policy should both promote education and training of treatment staff and organizational development of treatment CBOs. 

  14. 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.

  15. Addiction treatment provider attitudes on staff capacity and evidence-based clinical training: results from a national study.

    PubMed

    Lundgren, Lena; Amodeo, Maryann; Krull, Ivy; Chassler, Deborah; Weidenfeld, Rachel; de Saxe Zerden, Lisa; Gowler, Rebekah; Lederer, Jaime; Cohen, Alexander; Beltrame, Clelia

    2011-01-01

    This national study of addiction-treatment organizations' implementation of evidence-based practices examines: (1) organizational/leadership factors associated with director (n = 212) attitudes regarding staff resistance to organizational change, and (2) organizational/staff factors associated with staff (n = 312) attitudes regarding evidence-based clinical training. Linear regression analyses, controlling for type of treatment unit, leadership/staff characteristics and organizational readiness to change, identified that directors who perceived their organization needed more guidance and had less staff cohesion and autonomy rated staff resistance to organizational change significantly higher. Staff with higher levels of education and greater agreement that their organization supported change had greater preference for evidence-based trainings. Federal addiction treatment policy should both promote education and training of treatment staff and organizational development of treatment CBOs.  PMID:21477056

  16. A critical evaluation of the clinical evidence for pomegranate preparations in the prevention and treatment of cardiovascular diseases.

    PubMed

    Vlachojannis, Christian; Erne, Paul; Schoenenberger, Andreas W; Chrubasik-Hausmann, Sigrun

    2015-04-01

    This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit.

  17. A cluster randomized controlled trial to evaluate the effectiveness of the clinically integrated RHL evidence -based medicine course

    PubMed Central

    2010-01-01

    Background and objectives Evidence-based health care requires clinicians to engage with use of evidence in decision-making at the workplace. A learner-centred, problem-based course that integrates e-learning in the clinical setting has been developed for application in obstetrics and gynaecology units. The course content uses the WHO reproductive health library (RHL) as the resource for systematic reviews. This project aims to evaluate a clinically integrated teaching programme for incorporation of evidence provided through the WHO RHL. The hypothesis is that the RHL-EBM (clinically integrated e-learning) course will improve participants' knowledge, skills and attitudes, as well as institutional practice and educational environment, as compared to the use of standard postgraduate educational resources for EBM teaching that are not clinically integrated. Methods The study will be a multicentre, cluster randomized controlled trial, carried out in seven countries (Argentina, Brazil, Democratic Republic of Congo, India, Philippines, South Africa, Thailand), involving 50-60 obstetrics and gynaecology teaching units. The trial will be carried out on postgraduate trainees in the first two years of their training. In the intervention group, trainees will receive the RHL-EBM course. The course consists of five modules, each comprising self-directed e-learning components and clinically related activities, assignments and assessments, coordinated between the facilitator and the postgraduate trainee. The course will take about 12 weeks, with assessments taking place pre-course and 4 weeks post-course. In the control group, trainees will receive electronic, self-directed EBM-teaching materials. All data collection will be online. The primary outcome measures are gain in EBM knowledge, change in attitudes towards EBM and competencies in EBM measured by multiple choice questions (MCQs) and a skills-assessing questionniare administered eletronically. These questions have been

  18. Teaching evidence-based medicine to undergraduate medical students: a course integrating ethics, audit, management and clinical epidemiology.

    PubMed

    Rhodes, Martin; Ashcroft, Richard; Atun, Rifat A; Freeman, George K; Jamrozik, Konrad

    2006-06-01

    A six-week full time course for third-year undergraduate medical students at Imperial College uniquely links evidence-based medicine (EBM) with ethics and the management of change in health services. It is mounted jointly by the Medical and Business Schools and features an experiential approach. Small teams of students use a problem-based strategy to address practical issues identified from a range of clinical placements in primary and secondary care settings. The majority of these junior clinical students achieve important objectives for learning about teamwork, critical appraisal, applied ethics and health care organisations. Their work often influences the care received by patients in the host clinical units. We discuss the strengths of the course in relation to other accounts of programmes in EBM. We give examples of recurring experiences from successive cohorts and discuss assessment issues and how our multi-phasic evaluation informs evolution of the course and the potential for future developments.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  20. 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

  1. 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

  2. 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.

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

    PubMed

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

    1990-05-25

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

  4. Creating and using real-world evidence to answer questions about clinical effectiveness.

    PubMed

    de Lusignan, Simon; Crawford, Laura; Munro, Neil

    2015-01-01

    New forms of evidence are needed to complement evidence generated from randomised controlled trials (RCTs). Real-World Evidence (RWE) is a potential new form of evidence, but remains undefined. This paper sets to fill that gap by defining RWE as the output from a rigorous research process which: (1) includes a clear a priori statement of a hypothesis to be tested or research question to be answered; (2) defines the data sources that will be used and critically appraises their strengths and weaknesses; and (3) applies appropriate methods, including advanced analytics. These elements should be set out in advance of the study commencing, ideally in a published protocol.The strengths of RWE studies are that they are more inclusive than RCTs and can enable an evidence base to be developed around real-world effectiveness and to start to address the complications of managing other real-world problems such as multimorbidity. Computerised medical record systems and big data provide a rich source of data for RWE studies. However, guidance is needed to help assess the rigour of RWE studies so that the strength of recommendations based on their output can be determined. Additionally, RWE advanced analytics methods need better categorisation and validation.We predict that the core role of RCTs will shift towards assessing safety and achieving regulatory compliance. RWE studies, notwithstanding their limitations, may become established as the best vehicle to assess efficacy.

  5. Familial acromegaly: a specific clinical entity--further evidence from the genetic study of a three-generation family.

    PubMed

    Benlian, P; Giraud, S; Lahlou, N; Roger, M; Blin, C; Holler, C; Lenoir, G; Sallandre, J; Calender, A; Turpin, G

    1995-10-01

    Familial acromegaly is a very rare inherited disorder, characterized by the clustering within a single family of several related cases with somatotroph adenomas and acromegaly. The causes of these dominantly inherited pituitary tumours remain unknown. Although these families have a clinical presentation distinct from that of multiple endocrine neoplasia type 1 (MEN-1), the question of this syndrome as being linked to the MEN-1 locus has remained open. Our aim was to study a three-generation family with cases of acromegaly in a mother and her son, to explore better the clinical presentation of the disease, its pattern of inheritance and to test the hypothesis of a genetic linkage to the MEN-1 locus using closely linked polymorphic genetic markers. The refined analysis of 15 unaffected relatives revealed miscellaneous non-specific endocrine dysfunctions and the presence of multiple lipomata, as noted previously in some cases. Moreover, the notion of acromegalo-gigantism in the maternal grandmother and an incomplete penetrance appeared even more typical, suggesting that familial acromegaly is a specific clinical entity. Finally, under the hypotheses assumed for segregation analysis, no clinical, biological or genetic evidence of linkage to the MEN-1 locus could be retained in this family. However, these conclusions were limited because of incomplete penetrance and uncertain definition of the carrier status. Therefore, we conclude that further identification of the genetic predisposition to familial acromegaly might be obtained from the combined molecular genetic analysis of several families presenting with the same clinical features. PMID:7581969

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Retailing research: increasing the role of evidence in clinical services for childbirth.

    PubMed

    Lomas, J

    1993-01-01

    A current review of the structures and assumptions of research transfer for clinical care reveals some progress from "passive diffusion" to "active dissemination" models, but little or no progress has been made toward targeting local influences on practitioner behavior for "coordinated implementation" of clinically relevant research into childbirth (or other) medical practices. The implementation of scientifically valid research syntheses, such as Effective Care in Pregnancy and Childbirth (ECPC), is therefore constrained by a poorly developed marketplace for retailing research information to practitioners. A survey in Canada of the four most significant potential retailing groups demonstrated that whereas clinical and community groups were adopting the necessary knowledge and attitudes, public policy makers and administrators trailed well behind them. To increase the probability of thorough retailing of ECPC, a three-phase plan could be instituted that would identify product champions within potential retailing groups, develop implementation activities for each retailing group, and convene annual conferences. PMID:8413070

  11. 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…

  12. 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…

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Diversity of the ectoines biosynthesis genes in the salt tolerant Streptomyces and evidence for inductive effect of ectoines on their accumulation.

    PubMed

    Sadeghi, Akram; Soltani, Bahram M; Nekouei, Mojtaba Khayam; Jouzani, Gholamreza Salehi; Mirzaei, Hossein Hadavand; Sadeghizadeh, Majid

    2014-01-01

    Streptomyces commonly produce ectoines as compatible solutes to prevent osmotic stresses. Fine structure of the genes producing ectoine (ectC) and hydroxyectoine (ectD) enzymes in Streptomyces rimosus C-2012 as a slightly halophilic bacterium is reported in this study. Deduced amino acid sequences of ectC and ectD genes from strain C-2012 and some other related species were compared and 72-90% and 13-81% identities were detected for ectC and ectD, respectively. High similarity of ectC between closely or distantly related Streptomyces to the strain C-2012 may indicate horizontal transfer of this gene. However, phylogenetic relationships of ectD were correlated with phylogenetic affiliation of the strains. It suggests that the ability of Streptomyces to produce hydroxyectoine has been the result of a vertical transfer event. HPLC analysis showed that strain C-2012 was able to produce ectoine and hydroxyectoine both in the presence and absence of external salinity (up to 0.45 M NaCl). Accordingly, reverse transcription quantitative PCR (RT-qPCR) showed that ectABCD operon in this strain is positively affected by salt. Also, inductive effect of the salt was increased when it was applied with 1 mM of ectoines. Transcription level of ectC was increased 2.7- and 2.9-fold in the medium supplied with salt and ectoine and salt and hydroxyectoine, respectively. The effect of salinity with or without ectoines was more on ectD transcription level than that of ectC. In S. rimosus under salt stress, ectoine and hydroxyectoine biosynthesis primarily depends on the stimulation of ectABCD operon transcription. However, drastic accumulation of ectoine and hydroxyectoine without increase in ectC and ectD transcripts was observed in the medium supplied with salt and ectoines and that suggest there might be additional posttranscriptional level of control. Increases in ratio of some intracellular free amino acids in salt stressed to unstressed conditions were observed in cells grown with

  1. Competency in health care management: a training model in epidemiologic methods for assessing and improving the quality of clinical practice through evidence-based decision making.

    PubMed

    Hudak, R P; Jacoby, I; Meyer, G S; Potter, A L; Hooper, T I; Krakauer, H

    1997-01-01

    This article describes a training model that focuses on health care management by applying epidemiologic methods to assess and improve the quality of clinical practice. The model's uniqueness is its focus on integrating clinical evidence-based decision making with fundamental principles of resource management to achieve attainable, cost-effective, high-quality health outcomes. The target students are current and prospective clinical and administrative executives who must optimize decision making at the clinical and managerial levels of health care organizations.

  2. 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…

  3. 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…

  4. Evidence-Based Assessment for Children and Adolescents: Issues in Measurement Development and Clinical Application

    ERIC Educational Resources Information Center

    Kazdin, Alan E.

    2005-01-01

    Advances in measurement of child and adolescent social, emotional, and behavioral functioning and clinical disorders have been remarkable and remarkably reviewed in the prior articles. This commentary identifies common themes that emerge from the articles, discusses the proliferation of measures, and raises considerations regarding how one might…

  5. 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.

  6. 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…

  7. 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…

  8. 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…

  9. 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

  10. Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia?

    PubMed Central

    LAWRIE, STEPHEN M.; OLABI, BAYANNE; HALL, JEREMY; McINTOSH, ANDREW M.

    2011-01-01

    A diagnosis of schizophrenia, as in most of psychiatric practice, is made largely by eliciting symptoms with reference to subjective, albeit operationalized, criteria. This diagnosis then provides some rationale for management. Objective diagnostic and therapeutic tests are much more desirable, provided they are reliably measured and interpreted. Definite advances have been made in our understanding of schizophrenia in recent decades, but there has been little consideration of how this information could be used in clinical practice. We review here the potential utility of the strongest and best replicated risk factors for and manifestations of schizophrenia within clinical, epidemiological, cognitive, blood biomarker and neuroimaging domains. We place particular emphasis on the sensitivity, specificity and predictive power of pathophysiological indices for making a diagnosis, establishing an early diagnosis or predicting treatment response in schizophrenia. We conclude that a number of measures currently available have the potential to increase the rigour of clinical assessments in schizophrenia. We propose that the time has come to more fully evaluate these and other well replicated abnormalities as objective potential diagnostic and prognostic guides, and to steer future clinical, therapeutic and nosological research in this direction. PMID:21379347

  11. 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…

  12. 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…

  13. 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…

  14. 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

  15. Evidence supporting primary prevention of cardiovascular diseases with statins: Gaps between updated clinical results and actual practice.

    PubMed

    Bruckert, Eric; Ferrières, Jean

    2014-03-01

    The use of pharmacological lipid-lowering intervention in individuals with hypercholesterolaemia and known cardiovascular disease or diabetes/chronic kidney disease is well established. Current European Society of Cardiology guidelines recommend immediate initiation of drugs in adjunct to lifestyle intervention in these patients at high or very high cardiovascular risk. In these clinical settings, statins are generally chosen as the first-choice drug intervention, in consideration of the robust evidence showing a reduction in all-cause mortality and major adverse cardiac events (MACE). In contrast, primary prevention with statins, even in the subset of patients at high-risk of cardiovascular events, is not well implemented. This might be related to a lack of public awareness regarding the actual risk associated with prolonged exposure to high concentrations of low-density lipoprotein cholesterol (LDL-C) and uncertainties in the clinical evidence coming from the earliest trials in this patient subset. However, recent observational studies suggest that lowering LDL-C earlier in life and for a longer duration can substantially decrease the burden of cardiovascular disease and mortality. Moreover, results from recent well-conducted large meta-analyses of randomized clinical trials showed that primary prevention with statins reduced all-cause mortality by 14% and MACE by > 20% - findings similar to those observed for the use of statins in secondary prevention. Recently published American Heart Association/American College of Cardiology guidelines on the treatment of blood cholesterol emphasize that primary prevention using high-dose statins in individuals with LDL-C ≥ 190 mg/dL induces a benefit in atherosclerotic cardiovascular risk reduction that clearly exceeds the potential for adverse effects. We aim in this review to discuss the new data that advocate the use of statins in primary prevention earlier and more frequently, putting the efficacy evidence into

  16. 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. PMID:27713275

  17. Genetic susceptibility to retinopathy of prematurity: the evidence from clinical and experimental animal studies.

    PubMed

    Holmström, Gerd; van Wijngaarden, Peter; Coster, Douglas J; Williams, Keryn A

    2007-12-01

    Despite advances in management and treatment, retinopathy of prematurity remains a major cause of childhood blindness. Evidence for a genetic basis for susceptibility to retinopathy of prematurity is examined, including the influences of sex, ethnicity, and ocular pigmentation. The role of polymorphisms is explored in the genes for vascular endothelial growth factor and insulin-like growth factor-1, and of mutations in the Norrie disease gene. Insights into the genetic basis of retinopathy of prematurity provided by the animal model of oxygen induced retinopathy are examined. Evidence for a genetic component for susceptibility to retinopathy of prematurity is strong, although the molecular identity of the gene or genes involved remains uncertain. PMID:18024814

  18. 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.

  19. Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence.

    PubMed

    Foley, P A; Quirk, C; Sullivan, J R; Dolianitis, C; Hack, S P; Thirunavukkarasu, K; Cooper, A J

    2010-10-01

    Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short-term, their use is often limited by concerns over long-term toxicity, including end-organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long-term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.

  20. 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

  1. Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation.

    PubMed

    Blaze, Jennifer; Roth, Tania L

    2015-07-01

    While it is well-known that stress during development and adulthood can confer long-term neurobiological and behavioral consequences, investigators have only recently begun to assess underlying epigenetic modifications. In this review, we highlight clinical research and work from animal models that provide evidence of the impact of stressful experiences either during the perinatal period or adulthood on DNA methylation and behavior. Additionally, we explore the more controversial concept of transgenerational inheritance, including that associated with preconception stress experienced by the mother or father. Finally, we discuss challenges associated with the idea of transgenerational epigenetics and for the field of epigenetics in general.

  2. 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

  3. 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

  4. 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

  5. A pilot project using evidence-based clinical pathways and payment reform in China's rural hospitals shows early success.

    PubMed

    Cheng, Tsung-Mei

    2013-05-01

    Reforming China's public hospitals to curb widespread overtreatment and improve the quality and affordability of care has been the most challenging aspect of that nation's ambitious health reform, which began in 2009. This article describes a pilot project under way in several of China's provinces that combines payment reform with the implementation of evidence-based clinical pathways at a few hospitals serving rural areas. Results to date include reduced length-of-stay and prescription drug use and higher patient and provider satisfaction. These early results suggest that the pilot may be achieving its goals, which may have far-reaching and positive implications for China's ongoing reform.

  6. 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).

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Policies and Procedures That Facilitate Implementation of Evidence-Based Clinical Guidelines in U.S. Dental Schools.

    PubMed

    Polk, Deborah E; Nolan, Beth A D; Shah, Nilesh H; Weyant, Robert J

    2016-01-01

    The aim of this study was to determine the degree to which dental schools in the United States have policies and procedures in place that facilitate the implementation of evidence-based clinical guidelines. The authors sent surveys to all 65 U.S. dental schools in 2014; responses were obtained from 38 (58%). The results showed that, of the nine policies and procedures examined, only two were fully implemented by 50% or more of the responding schools: guidelines supported through clinical faculty education or available chairside (50%), and students informed of guidelines in both the classroom and clinic (65.8%). Although 92% of the respondents reported having an electronic health record, 80% of those were not using it to track compliance with guidelines. Five schools reported implementing more policies than the rest of the schools. The study found that the approach to implementing guidelines at most of the responding schools did not follow best practices although five schools had an exemplary set of policies and procedures to support guideline implementation. These results suggest that most dental schools are currently not implementing guidelines effectively and efficiently, but that the goal of schools' having a comprehensive implementation program for clinical guidelines is achievable since some are doing so. Future studies should determine whether interventions to improve implementation in dental schools are needed. PMID:26729681

  12. 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.

  13. The potential use of GABA agonists in psychiatric disorders: evidence from studies with progabide in animal models and clinical trials.

    PubMed

    Lloyd, K G; Morselli, P L; Depoortere, H; Fournier, V; Zivkovic, B; Scatton, B; Broekkamp, C; Worms, P; Bartholini, G

    1983-06-01

    Progabide, a new antiepileptic GABA agonist of moderate affinity for GABA receptors, has been studied in a number of psychiatric disorders and the results compared with the action of this drug in animal models. In an animal model for anxiety (the aversive response to periaqueductal grey stimulation in the rat) progabide had a similar action to that of diazepam. However in clinical trials to date the effect of the GABA agonist was inferior to that of benzodiazepines. As progabide diminishes both the nigrostriatal dopamine neuron activity and the effects of striatal dopamine receptor activation, a trial in schizophrenic patients was undertaken. Progabide was devoid of any evident antipsychotic action. However a certain improvement in responsiveness to the environment and in social interactions was noticed in hebephrenic and schizoaffective syndromes. This lack of antipsychotic effect of progabide may be a reflection of the weak activity of GABA agonists on limbic dopamine neurons. In these various clinical trials a definite improvement of affect and mood was noted in those patients receiving progabide. In clinical trials in depressed patients progabide produces a significant reduction in depressive symptoms, an action similar to that of imipramine both for the global clinical rating and the HRSD. This antidepressant activity is reflected by the action of progabide in behavioural models of depression such as olfactory bulbectomy, learned helplessness and the sleep-wake cycle.

  14. Tailoring mTOR-based therapy: molecular evidence and clinical challenges

    PubMed Central

    Santulli, Gaetano; Totary-Jain, Hana

    2013-01-01

    The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism. The mTOR pathway is dysregulated in a number of human pathologies including cancer, diabetes, obesity, autoimmune disorders, neurological disease and aging. Ongoing clinical trials testing mTOR-targeted treatments number in the hundreds and underscore its therapeutic potential. To date mTOR inhibitors are clinically approved to prevent organ rejection, to inhibit restenosis after angioplasty, and to treat several advanced cancers. In this review we discuss the continuously evolving field of mTOR pharmacogenomics, as well as highlight the emerging efforts in identifying diagnostic and prognostic markers, including miRNAs, in order to assess successful therapeutic responses. PMID:24024901

  15. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach.

    PubMed

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-09-24

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  16. Vonoprazan-based therapy for Helicobacter pylori eradication: experience and clinical evidence

    PubMed Central

    Akazawa, Yuko; Fukuda, Daisuke; Fukuda, Yutaka

    2016-01-01

    Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H. pylori eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors. PMID:27803739

  17. Evidence-based guidelines for pediatric clinical trials: focus on StaR Child Health.

    PubMed

    Sampson, Mario R; Benjamin, Daniel K; Cohen-Wolkowiez, Michael

    2012-09-01

    Clinical trials in children are challenging and filled with important ethical considerations that differ from adults. Given difficulties associated with pediatric clinical trials, off-label prescribing is a common practice in pediatrics, which can lead to adverse safety events and efficacy failures. To overcome these consequences, in the past 15 years, legislation in the USA and Europe has provided incentives to industry and increased government funding to conduct pediatric trials. Pediatric trial networks have also been formed to decrease the knowledge gap. However, challenges to performing pediatric trials and lack of standardization and guidelines regarding studies in children still exist. Standards for Research (StaR) in Child Health, begun in 2009, aims to improve the design, conduct and reporting of pediatric trials. This organization uses a consensus guideline approach involving academic, government and industry stakeholders to identify and disseminate best practices for pediatric trials. Six out of 11 planned standards are currently published.

  18. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    PubMed Central

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers.

  19. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    PubMed Central

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  20. Carney v Newton: expert evidence about the standard of clinical notes.

    PubMed

    Faunce, Thomas; Hammer, Ingrid; Jefferys, Susannah

    2007-12-01

    In Carney v Newton [2006] TASSC 4 the Tasmanian Supreme Court heard a claim that the defendant breached his duty of care by failing to properly diagnose and treat a node positive carcinoma in the plaintiff's breast tissue. At trial, argument turned on the actual dialogue that took place during the initial consultation, with significant reliance on the clinical notes of the defendant. The court gave considerable weight to "expert" witnesses in ascertaining the acceptability of the defendant's conduct concerning the maintenance and interpretation of his clinical notes. This raises important questions in relation to proof of quality of medical records as part of the current professional standard of care, as modified by recent legislation in most jurisdictions.

  1. 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

  2. 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

  3. Evidence of the Internationalization of Clinical Endoscopy Based on Journal Metrics

    PubMed Central

    2015-01-01

    Background/Aims This study aims to verify the internationalization of Clinical Endoscopy based on journal metrics after the change to English-only in 2011. The results of this study serve as a starting point for developing strategies to develop Clinical Endoscopy into a top-tier international journal. Methods The following journal metrics were analyzed from the journal's homepage or the Web of Science: the number of citable articles, number of countries of affiliation of the contributors, the number of articles supported by research grants, total citations, impact factor, citing journals, countries of citing authors, and the Hirsch index. Results The number of citable articles in 2011, 2012, 2013, and 2014 was 22, 81, 120, and 95, respectively. The authors were from 11 countries. Twenty-one out of 55 original articles were supported by research grants. The total citations in 2012, 2013, and 2014 were 2, 85, and 213, respectively. The impact factor was 0.670 in 2013 and 0.940 in 2014. The number of countries citing authors were from was 61. The Hirsch index was 6. Conclusions The above results demonstrate that Clinical Endoscopy became an international journal, contributing to the propagation of valuable research results through an open access publishing model. PMID:26240806

  4. Healthcare-seeking behaviour in rural Ethiopia: evidence from clinical vignettes

    PubMed Central

    Mebratie, Anagaw D; Van de Poel, Ellen; Yilma, Zelalem; Abebaw, Degnet; Alemu, Getnet; Bedi, Arjun S

    2014-01-01

    Objectives To investigate the determinants of healthcare-seeking behaviour using five context-relevant clinical vignettes. The analysis deals with three issues: whether and where to seek modern care and when to seek care. Setting This study is set in 96 villages located in four main regions of Ethiopia. The participants of this study are 1632 rural households comprising 9455 individuals. Primary and secondary outcome measures Probability of seeking modern care for symptoms related to acute respiratory infections/pneumonia, diarrhoea, malaria, tetanus and tuberculosis. Conditional on choosing modern healthcare, where to seek care (health post, health centre, clinic and hospital). Conditional on choosing modern healthcare, when to seek care (seek care immediately, the next day, after 2 days, between 3 days to 1 week, a week or more). Results We find almost universal preference for modern care. Foregone care ranges from 0.6% for diarrhoea to 2.5% for tetanus. There is a systematic relationship between socioeconomic status and choice of providers mainly for adult-related conditions with households in higher consumption quintiles more likely to seek care in health centres, private/Non-Government Organization (NGO) clinics as opposed to health posts. Delays in care-seeking behaviour are apparent mainly for adult-related conditions and among poorer households. Conclusions The analysis suggests that the lack of healthcare utilisation is not driven by the inability to recognise health problems or due to a low perceived need for modern care. PMID:24525391

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

    PubMed Central

    Pasieka, Aoibhe M.; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  6. Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

    PubMed Central

    2016-01-01

    Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose. PMID:27721835

  7. 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

  8. 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

  9. Clinical metric and medication persistency effects: evidence from a Medicaid care management program.

    PubMed

    Berg, Gregory D; Leary, Fredric; Medina, Wendie; Donnelly, Shawn; Warnick, Kathleen

    2015-02-01

    The objective was to estimate clinical metric and medication persistency impacts of a care management program. The data sources were Medicaid administrative claims for a sample population of 32,334 noninstitutionalized Medicaid-only aged, blind, or disabled patients with diagnosed conditions of asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes, or heart failure between 2005 and 2009. Multivariate regression analysis was used to test the hypothesis that exposure to a care management intervention increased the likelihood of having the appropriate medication or procedures performed, as well as increased medication persistency. Statistically significant clinical metric improvements occurred in each of the 5 conditions studied. Increased medication persistency was found for beta-blocker medication for members with coronary artery disease, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic medications for members with heart failure, bronchodilator and corticosteroid medications for members with chronic obstructive pulmonary disease, and aspirin/antiplatelet medications for members with diabetes. This study demonstrates that a care management program increases the likelihood of having an appropriate medication dispensed and/or an appropriate clinical test performed, as well as increased likelihood of medication persistency, in people with chronic conditions.

  10. Bullous keratopathy as a progressive disease: evidence from clinical and laboratory imaging studies.

    PubMed

    Morishige, Naoyuki; Sonoda, Koh-Hei

    2013-11-01

    Bullous keratopathy is categorized as a corneal endothelial disease. However, pathological changes, including subepithelial fibrosis and the accumulation of extracellular matrix, have been detected in the corneal stroma of individuals with this condition. In vivo confocal microscopy allows the visualization of human corneal cellular structures and has provided information regarding how eyes are affected by various diseases. However, the determination of disease pathogenesis on the basis of in vivo confocal microscopic observations is problematic. We evaluated the structural alterations in the corneal stroma of eyes affected by bullous keratopathy using second harmonic generation microscopy and laser confocal immunofluorescence microscopy of whole-mount preparations. Using these approaches, we detected the transdifferentiation of keratocytes into fibroblasts and myofibroblasts at the anterior and posterior stroma and the presence of subepithelial fibrosis at the anterior stroma and disorganized collagen lamellae at the posterior stroma of the bullous keratopathy cornea. These changes were only detected in specimens from eyes with stromal edema lasting at least 12 months. Similar time-dependent changes were apparent by using in vivo confocal microscopy in the corneal stroma of patients with bullous keratopathy after performing a Descemet stripping automated endothelial keratoplasty surgery and were associated with an unfavorable outcome with regard to postoperative visual acuity. Our observations suggest that pathological changes in the corneal stroma of patients with bullous keratopathy are progressive and affect postoperative visual acuity after a Descemet stripping automated endothelial keratoplasty surgery is performed. PMID:24104939

  11. Screening for Maternal Thyroid Dysfunction in Pregnancy: A Review of the Clinical Evidence and Current Guidelines

    PubMed Central

    Chang, Donny L. F.; Pearce, Elizabeth N.

    2013-01-01

    Observational studies have demonstrated that maternal thyroid dysfunction and thyroid autoimmunity in pregnancy may be associated with adverse obstetric and fetal outcomes. Treatment of overt maternal hyperthyroidism and overt hypothyroidism clearly improves outcomes. To date there is limited evidence that levothyroxine treatment of pregnant women with subclinical hypothyroidism, isolated hypothyroxinemia, or thyroid autoimmunity is beneficial. Therefore, there is ongoing debate regarding the need for universal screening for thyroid dysfunction during pregnancy. Current guidelines differ; some recommend an aggressive case-finding approach, whereas others advocate testing only symptomatic women or those with a personal history of thyroid disease or other associated medical conditions. PMID:23762776

  12. 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

  13. 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

  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. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

    PubMed Central

    Dürsteler, Kenneth M; Berger, Eva-Maria; Strasser, Johannes; Caflisch, Carlo; Mutschler, Jochen; Herdener, Marcus; Vogel, Marc

    2015-01-01

    Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by

  16. 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.

  17. 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.

  18. 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

  19. Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence

    PubMed Central

    Du, Yixing; Xu, Xiaohan; Chu, Ming; Guo, Yan

    2016-01-01

    Air pollution is now becoming an independent risk factor for cardiovascular morbidity and mortality. Numerous epidemiological, biomedical and clinical studies indicate that ambient particulate matter (PM) in air pollution is strongly associated with increased cardiovascular disease such as myocardial infarction (MI), cardiac arrhythmias, ischemic stroke, vascular dysfunction, hypertension and atherosclerosis. The molecular mechanisms for PM-caused cardiovascular disease include directly toxicity to cardiovascular system or indirectly injury by inducing systemic inflammation and oxidative stress in peripheral circulation. Here, we review the linking between PM exposure and the occurrence of cardiovascular disease and discussed the possible underlying mechanisms for the observed PM induced increases in cardiovascular morbidity and mortality. PMID:26904258

  20. Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results

    PubMed Central

    Diel, I J; Mundy, G R

    2000-01-01

    Several animal models, as well as a number of cell culture experiments, indicate a prophylactic effect of bisphosphonates in respect of subsequent bone metastasis. Moreover, in preliminary clinical trials involving patients with advanced breast cancer and local or remote metastases, biophosphonates produced a reduction in new skeletal metastases. This overview summarizes and discusses the results of the latest investigations. It opens with a section on the pathophysiology of bone metastasis, which is followed by a report on animal models and first studies of bisphosphonate treatment as a new approach in systemic adjuvant therapy. © 2000 Cancer Research Campaign PMID:10780514

  1. Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats.

    PubMed

    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 (10(3), 10(5), 10(8) 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 10(3) 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 10(5) and 10(8) 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

  2. Ibrutinib in Waldenström macroglobulinemia: latest evidence and clinical experience

    PubMed Central

    Castillo, Jorge J.; Palomba, M. Lia; Advani, Ranjana; Treon, Steven P.

    2016-01-01

    Ibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events. PMID:27493708

  3. Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats.

    PubMed

    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 (10(3), 10(5), 10(8) 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 10(3) 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 10(5) and 10(8) 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

  4. Involvement of consumers in the development of evidence based clinical guidelines: practical experiences from the North of England evidence based guideline development programme

    PubMed Central

    van Wersch, A; Eccles, M

    2001-01-01

    Background—Consumer involvement in clinical guidelines has long been advocated although there are few empirical accounts of attempts to do so. It is therefore not surprising that there is a lack of clarity about how and when to involve consumers and what to expect from them within the process of guideline development. Methods—The North of England evidence based guideline development programme has used four different methods of consumer involvement. Results—When individual patients were included in a guideline development group they contributed infrequently and had problems with the use of technical language. Although they contributed most in discussions of patient education, their contributions were not subsequently acted on. In a "one off" meeting with a group of patients there were again reported problems with medical terminology and the group were most interested in sections on patient education and self management. However, their understanding of the use of scientific evidence in order to contribute to a more cost effective health care remained unclear. In a workshop it was possible to explain the technical elements of guideline development to patients who could then engage with such a process and make relevant suggestions as a consequence. However, this was relatively resource intensive. A patient advocate within a guideline development group felt confidence to speak, was used to having discussions with health professionals, and was familiar with the medical terminology. Conclusions—Consumers should be involved in all stages of guideline development. While this is possible, it is not straightforward. There is no one right way to accomplish this and there is a clear need for further work on how best to achieve it. Key Words: patient involvement; patient education; guideline development groups PMID:11239138

  5. Problems in the reporting of acne clinical trials: a spot check from the 2009 Annual Evidence Update on Acne Vulgaris.

    PubMed

    Ingram, John R; Grindlay, Douglas J C; Williams, Hywel C

    2010-07-12

    In the course of producing the 2009 NHS Evidence--skin disorders Annual Evidence Update on Acne Vulgaris, 25 randomised controlled trials were examined. From these, at least 12 potentially serious problems of trial reporting were identified. Several tr