Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain

Background - The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms. Materials and methods - In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0\u2013100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment. Results - Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy. Conclusions - Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects

Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

<p>Abstract</p> <p>Background</p> <p>There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology.</p> <p>Results</p> <p>In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv) isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge.</p> <p>Conclusion</p> <p>A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans.</p> <p>Crown Copyright © 2009</p

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls

<p>Abstract</p> <p>Background</p> <p>Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization.</p> <p>Methods</p> <p>Fourteen female temporomandibular disorders (TMD) subjects with myofascial pain (RDC/TMD Ia or Ib) and arthralgia (RDC/TMD IIIa) were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid-ventral surface of forearm. Pain intensity (0–10) was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2–12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC). A receiver operating characteristic (ROC) curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus.</p> <p>Results</p> <p>Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites.</p> <p>Conclusion</p> <p>The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test.</p

ANALOGUE SAMPLES IN AN EUROPEAN SAMPLE CURATION FACILITY - THE EURO-CARES PROJECT.

The objective of the H2020-funded EURO-CARES project (grant agreement n° 640190) was to create a roadmap for the implementation of a European Extraterrestrial Sample Curation Facility (ESCF) that would be suitable for the curation of samples from all possible return missions likely over the next few decades, i.e. from the Moon, asteroids and Mars. The return of extraterrestrial samples brought to Earth will require specific storage conditions and handling procedures, in particular for those coming from Mars. For practical reasons and sterility concerns it might be necessary for such a facility to have its own collection of analogue samples permitting the testing of storage conditions, and to develop protocols for sample prepartion and analyses. Within the framework of the EURO-CARES project, we havecreated a list of the different types of samples that would be relevant for such a curation facility. The facility will be used for receiving and opening of the returned sample canisters, as well as for handling and preparation of the returned samples. Furthermore, it will provide some analysis of the returned samples, i.e. early sample characterisation, and is expected to provide longterm storage of the returned samples. Each of these basic functions requires special equipment. Equipment, handling protocols and long-term storage conditions will strongly depend on the characteristics of the materials, and on whether returned samples are from the Moon, Mars or an asteroidal body. Therefore the different types and aspects of analogue samples one need to be considered, i.e. the nature of the materials, which analogues are needed for what purpose, what mass is needed, and how should the analogue samples be stored within the facility. We distinguished five different types of anologue samples: analogue (s.s.), witness plate, voucher specimen, reference sample, and standard. Analogues are materials that have one or more physical or chemical properties similar to Earth-returned extraterrestrial samples. Reference samples are well-characterised materials with known physical and chemical properties used for testing. They may not necessarily be the same materials as the analogues defined above. Standards are internationally recognised, homogeneous materials with known physical and chemical properties that are used for calibration. They can also be used as reference samples in certain circumstances. They may be made of natural materials but are often produced artificially. A voucher specimen is a duplicate of materials used at any stage during sample acquisition, storage, transport, treatment etc., e.g. spacecraft materials (including solar panels), lubricants, glues, gloves, saws, drills, and others. In addition, Earth landing site samples (from the touch down site) would be necessary in case of doubtful analysis, even if normally this type of contamination is not expected. Finally, a witness plate is defined as material left in an area where work is being done to detect any biological, particulate, chemical, and/or organic contamination. It is a spatial and temporal document of what happens in the work area. Analogue materials could be solids (including ices), liquids or gases. These could contain biological (extant and/or exinct) and/or organic components. They could be natural materials, e.g. rocks or minerals, or could be manufactured, such as mixtures of different components, which may be biologically and/or organically doped. Analogues with appropriate sample size and nature will be well-suited for testing and training of sample handling procedures, and for transport protocols. The training of science and curation teams also requires reference samples and standards. Long-term storage needs special witness plates and voucher specimes. Developing and testing sample preparation protocols needs all sample types

The IASP classification of chronic pain for ICD-11: chronic cancer-related pain.

Worldwide, the prevalence of cancer is rising and so too is the number of patients who survive their cancer for many years thanks to the therapeutic successes of modern oncology. One of the most frequent and disabling symptoms of cancer is pain. In addition to the pain caused by the cancer, cancer treatment may also lead to chronic pain. Despite its importance, chronic cancer-related pain is not represented in the current International Classification of Diseases (ICD-10). This article describes the new classification of chronic cancer-related pain for ICD-11. Chronic cancer-related pain is defined as chronic pain caused by the primary cancer itself or metastases (chronic cancer pain) or its treatment (chronic postcancer treatment pain). It should be distinguished from pain caused by comorbid disease. Pain management regimens for terminally ill cancer patients have been elaborated by the World Health Organization and other international bodies. An important clinical challenge is the longer term pain management in cancer patients and cancer survivors, where chronic pain from cancer, its treatment, and unrelated causes may be concurrent. This article describes how a new classification of chronic cancer-related pain in ICD-11 is intended to help develop more individualized management plans for these patients and to stimulate research into these pain syndromes

Neuropathic cancer pain: Prevalence, severity, analgesics and impact from the European Palliative Care Research Collaborative–Computerised Symptom Assessment study

Background: Neuropathic pain causes greater pain intensity and worse quality of life than nociceptive pain. There are no published data that confirm this in the cancer population. Aim: We hypothesised that patients with neuropathic cancer pain had more intense pain, experienced greater suffering and were treated with more analgesics than those with nociceptive cancer pain, and a neuropathic pain screening tool, painDETECT, would perform as well in those with cancer pain as is reported in those with non-cancer pain. Design: The data were obtained from an international cross-sectional observational study. Setting/Participants: A total of 1051 patients from inpatients and outpatients, with incurable cancer completed a computerised assessment on symptoms, function and quality of life. In all, 17 centres within eight countries participated. Medical data were recorded by physicians. Pain type was a clinical diagnosis recorded on the Edmonton Classification System for Cancer Pain. Results: Of the patients, 670 had pain: 534 with nociceptive pain, 113 with neuropathic pain and 23 were unclassified. Patients with neuropathic cancer pain were significantly more likely to be receiving oncological treatment, strong opioids and adjuvant analgesia and have a reduced performance status. They reported worse physical, cognitive and social function. Sensitivity and specificity of painDETECT for identifying neuropathic cancer pain was less accurate than when used in non-cancer populations. Conclusions: Neuropathic cancer pain is associated with a negative impact on daily living and greater analgesic requirements than nociceptive cancer pain. Validated assessment methods are needed to enable early identification of neuropathic cancer pain, leading to more appropriate treatment and reduced burden on patients