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Bruix J.,University of Barcelona | Poynard T.,University Pierre and Marie Curie | Colombo M.,University of Milan | Schiff E.,University of Miami | And 14 more authors.
Gastroenterology | Year: 2011

Background & Aims: Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program. Methods: Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n = 311) or no treatment (controls, n = 315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event. Results: There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.8802.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.1302.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P = .016). There were no new safety observations. Conclusions: Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension. © 2011 AGA Institute.


Baron R.,Universitaetsklinikum Schleswig Holstein | Hans G.,University of Antwerp | Dickenson A.H.,University College London
Annals of Neurology | Year: 2013

Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.


Pfau D.B.,University of Heidelberg | Krumova E.K.,Ruhr University Bochum | Treede R.-D.,University of Heidelberg | Baron R.,Universitaetsklinikum Schleswig Holstein | And 8 more authors.
Pain | Year: 2014

Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST - according to the German Research Network on Neuropathic Pain - to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain. © 2014 Published by Elsevier B.V. on behalf of International Association for the Study ofPain. All rights reserved.


Stockburger M.,Charite - Medical University of Berlin | Gomez-Doblas J.J.,Campus Universitario Teatinos | Lamas G.,Columbia University | Alzueta J.,Campus Universitario Teatinos | And 7 more authors.
European Journal of Heart Failure | Year: 2011

AimsPrevious experimental and clinical studies have consistently suggested that right ventricular (RV) apical pacing has important adverse effects. Ventricular pacing (VP), however, is required, and cannot be reduced in many patients with atrioventricular (AV) block. The PREVENT-HF study was an international randomized trial that explored differences in left ventricular (LV) remodelling during RV apical vs. biventricular (BIV) pacing in patients with AV block.Methods and ResultsPatients with an expected VP prevalence <80 were assigned to RV apical or BIV pacing. The primary endpoint was the change in LV end-diastolic volume (EDV) >12 months. Secondary endpoints were LV end-systolic volume (ESV), LV ejection fraction (EF), mitral regurgitation (MR), and a combination of heart failure (HF) events and cardiovascular hospitalizations. Overall, 108 patients were randomized (RV: 58; BIV: 50). Intention to treat and on-treatment analyses revealed no significant differences in any of the outcomes. Analysis of covariance (ANCOVA) difference for treatment according to randomization (in mL): LVEDV -3.92 (-18.71 to 10.85), P 0.6; LVESV -1.38 (-12.07 to 9.31), P 0.80; LVEF 2.47 (-3.00 to 7.94), P 0.37. Analysis of covariance difference for the on-treatment analysis: LVEDV -4.90 (-20.02 to 10.22, PP 0.52; LVESV -6.45 (-17.28 to 4.38), P 0.24, LVEF 2.18 (-3.37 to 7.73), P 0.44. Furthermore, secondary endpoints did not differ significantly.ConclusionThis study did not demonstrate significant LV volume differences >12 months between RV apical and BIV pacing for AV block. Thus, BIV pacing cannot be recommended as a routine treatment for AV block in these patients. However, the results encourage and inform the design of subsequent larger trials with higher power for detecting small volume changes. © 2011 The Author.


Poggel D.A.,Otto Von Guericke University of Magdeburg | Poggel D.A.,University of Gottingen | Mueller I.,Otto Von Guericke University of Magdeburg | Kasten E.,Otto Von Guericke University of Magdeburg | And 3 more authors.
NeuroRehabilitation | Year: 2010

Objective: To determine the relationship of objective and subjective outcome measures of Vision Restoration Training (VRT) for visual field recovery in partially blind patients. This is of interest because the patient's subjective improvement cannot be inferred from objective changes in visual field charts. Design: Nineteen patients with visual system lesions underwent visual field tests (objective measure) before and after six months of VRT. Subjective outcome was determined by pre- and post-training interviews (open narration, questions on activities of daily living, ratings). Interview content was quantified by determining the response frequency for relevant content categories. Drawings of perceived visual field size were used as a subjective topographical measure. Subjective training results were compared to objective visual field size (perimetry). Results: Visual field size increased significantly over the training period. Patients' subjective evaluations depended on the size and location of regained areas, but also on specific evaluation of safe navigation, mobility, reading, and communication. Patients with objective increase of visual field size also reported subjective improvements in daily life. Conclusions: Computer-based training can improve visual field size as well as subjective visual performance. The patients' subjective experience should be included in treatment evaluation to ensure the meaningfulness of training beyond perimetric measures. © 2010 IOS Press and the authors. All rights reserved.

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