Search

Objective: To evaluate the role of 99mTc-labelled glucosamine [99mTc-ECDG] as a clinical biomarker for the early detection of interstitial lung disease (ILD) in systemic sclerosis (SSc). Methods: In this prospective pilot study, glucosamine scanning (GS) was performed in 15 SSc patients, with and without ILD. Collected data included patient disease characteristics, autoantibody profile, GS results, high-resolution computerised tomography [HRCT], pulmonary function tests [PFT], and transthoracic echocardiogram [TTE]. Glucosamine results were correlated with patient clinical profile, HRCT, and PFT's findings. Results: Lung uptake of 99mTc-ECDG was high in 4 patients, moderate in 3, mild in 5, and normal in 3 with SSc, respectively. Of the patients with high and moderate uptake there was a 100% correlation between 99mTc-ECDG uptake and HRCT showing ILD. Of the 5 patients with mild 99mTc-ECDG uptake, 4 patients had aspiration pneumonia, and 1 had early ILD using HRCT. Of the 3 patients with normal 99mTc-ECDG, 2 had normal HRCTs; the third had severe pulmonary arterial hypertension with minimal HRCT changes of ILD. High and moderate 99mTc-ECDG lung uptake predicted abnormal PFT's in 100% of cases. In 3 patients, there was less extensive disease depicted on the 99mTc-ECDG scans than on the HRCT. These patients demonstrated a more favourable outcome than would have been expected from the HRCT scans alone. Mild 99mTc-ECDG lung uptake correlated with abnormal PFT's in 60% of cases. The pattern of 99mTc-ECDG uptake was excellent (100%) at distinguishing metabolically active ILD from aspiration pneumonia. Diffuse uptake was noted in the former and patchy uptake in the latter disease entity. Conclusion: Increased 99mTc-ECDG uptake in scleroderma lung correlated positively with both structural and functional changes. 99mTc-ECDG is a useful adjunct helping elucidate inflammation secondary to aspiration pneumonia and/or other causes of abnormal PFT's. [ABSTRACT FROM AUTHOR]

Objective: Describe research methods used in priority-setting exercises for musculoskeletal conditions and synthesise the priorities identified., Design: Scoping review., Setting and Population: Studies that elicited the research priorities of patients/consumers, clinicians, researchers, policy-makers and/or funders for any musculoskeletal condition were included., Methods and Analysis: We searched MEDLINE and EMBASE from inception to November 2017 and the James Lind Alliance top 10 priorities, Cochrane Priority Setting Methods Group, and Cochrane Musculoskeletal and Back Groups review priority lists. The reported methods and research topics/questions identified were extracted, and a descriptive synthesis conducted., Results: Forty-nine articles fulfilled our inclusion criteria. Methodologies and stakeholders varied widely (26 included a mix of clinicians, consumers and others, 16 included only clinicians, 6 included only consumers or patients and in 1 participants were unclear). Only two (4%) reported any explicit inclusion criteria for priorities. We identified 294 broad research priorities from 37 articles and 246 specific research questions from 17 articles, although only four (24%) of the latter listed questions in an actionable format. Research priorities for osteoarthritis were identified most often (n=7), followed by rheumatoid arthritis (n=4), osteoporosis (n=4) and back pain (n=4). Nearly half of both broad and specific research priorities were focused on treatment interventions (n=116 and 111, respectively), while few were economic (n=8, 2.7% broad and n=1, 0.4% specific), implementation (n=6, 2% broad and n=4, 1.6% specific) or health services and systems research (n=15, 5.1% broad and n=9, 3.7% specific) priorities., Conclusions: While many research priority-setting studies in the musculoskeletal field have been performed, methodological limitations and lack of actionable research questions limit their usefulness. Future studies should ensure they conform to good priority-setting practice to ensure that the generated priorities are of maximum value., Prospero Registration Number: CRD42017059250., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Pacific Islands Fisheries Science Center deploys the Modular Optical Underwater Survey System (MOUSS) to estimate the species-specific, size-structured abundance of commercially-important fish species in Hawaii and the Pacific Islands. The MOUSS is an autonomous stereo-video camera system designed for the in situ visual sampling of fish assemblages. This system is rated to 500 m and its low-light, stereo-video cameras enable identification, counting, and sizing of individuals at a range of 0.5-10 m. The modular nature of MOUSS allows for the efficient and cost-effective use of various imaging sensors, power systems, and deployment platforms. The MOUSS is in use for surveys in Hawaii, the Gulf of Mexico, and Southern California. In Hawaiian waters, the system can effectively identify individuals to a depth of 250 m using only ambient light. In this paper, we describe the MOUSS's application in fisheries research, including the design, calibration, analysis techniques, and deployment mechanism., Competing Interests: The authors declare no conflict of interest.

Objective: Previously published literature assessing the reporting of outcome measures used in joint replacement randomized controlled trials (RCT) has revealed disappointing results. It remains unknown whether international initiatives have led to any improvement in the quality of reporting and/or a reduction in the heterogeneity of outcome measures used. Our objective was to systematically assess and compare primary outcome measures and the risk of bias in joint replacement RCT published in 2008 and 2013., Methods: We searched MEDLINE, EMBASE, and CENTRAL for RCT investigating adult patients undergoing joint replacement surgery. Two authors independently identified eligible trials, extracted data, and assessed risk of bias using the Cochrane tool., Results: Seventy RCT (30 in 2008, 40 in 2013) met the eligibility criteria. There was no significant difference in the number of trials judged to be at low overall risk of bias (n = 6, 20%) in 2008 compared with 2013 [6 (15%); chi-square = 0.302, p = 0.75]. Significantly more trials published in 2008 did not specify a primary outcome measure (n = 25, 83%) compared with 18 trials (45%) in 2013 (chi-square = 10.6316, p = 0.001). When specified, there was significant heterogeneity in the measures used to assess primary outcomes., Conclusion: While less than a quarter of trials published in both 2008 and 2013 were judged to be at low overall risk of bias, significantly more trials published in 2013 specified a primary outcome. Although this might represent a temporal trend toward improvement, the overall frequency of primary outcome reporting and the wide heterogeneity in primary outcomes reported remain suboptimal.

Background: It is not known, whether outcome reporting in trials of total joint arthroplasty in the recent years is adequate or not. Our objective was to assess whether outcomes reported in total joint replacement (TJR) trials fulfil the Outcome Measures in Rheumatology (OMERACT) Filter 2.0., Methods: We systematically reviewed all TJR trials in adults, published in English in 2008 or 2013. Searches were conducted in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Two authors independently applied the inclusion criteria for the studies, and any disagreement was resolved with a third review author. All outcome measures were abstracted using a pre-piloted standardised data extraction form and assessed for whether they mapped to one of the three OMERACT Filter 2.0 core areas: pathophysiological, life impact, and death., Results: From 1635 trials identified, we included 70 trials (30 in 2008 and 40 in 2013) meeting the eligibility criteria. Twenty-two (31%) trials reported the three essential OMERACT core areas. Among the 27 hip replacement surgery trials and 39 knee replacement surgery trials included, 11 hip (41%) and nine knee (23%) trials reported all three essential OMERACT core areas. The most common outcome domains/measures were pain (20/27, 74%) and function (23/27, 85%) in hip trials and pain (26/39, 67%) and function (27/39, 69%) in knee trials. Results were similar for shoulder and hand joint replacement trials., Conclusions: We identified significant gaps in the measurement of OMERACT core outcome areas in TJR trials, despite the majority reporting outcome domains of pain and function. An international consensus of key stakeholders is needed to develop a core domain set for reporting of TJR trials., Systematic Review Registration: PROSPERO CRD42014009216.

Objective: To develop a plan for harmonizing outcomes for people undergoing total joint replacement (TJR), to achieve consensus regarding TJR outcome research., Methods: The TJR working group met during the 2014 Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary. Multiple conference calls preceded the face-to-face meeting. Brief presentations were made during a 1.5-h meeting, which included an overview of published systematic reviews of TJR trials and the results of a recent systematic review of TJR clinical trial outcome domains and measures. This was followed by discussion of potential core set areas/domains for TJR clinical trials (as per OMERACT Filter 2.0) as well as the challenges associated with the measurement of these domains., Results: Working group participants discussed which TJR clinical trial outcome domains/areas map to the inner versus outer core for core domain set. Several challenges were identified with TJR outcomes including how to best measure function after TJR, elucidating the source of the pre- and post-TJR joint pain being measured, joint-specific versus generic quality of life instruments and the importance of patient satisfaction and revision surgery as outcomes. A preliminary core domain set for TJR clinical trials was proposed and included pain, function, patient satisfaction, revision, adverse events, and death. This core domain set will be further vetted with a broader audience., Conclusion: An international effort with active collaboration with the orthopedic community to standardize key outcome domains and measures is under way with the TJR working group. This effort will be further developed with new collaborations.

Aim: To develop Australian and New Zealand evidence-based recommendations for pain management by pharmacotherapy in adult patients with optimally treated inflammatory arthritis (IA)., Methods: Four hundred and fifty-three rheumatologists from 17 countries including 46 rheumatologists from Australia and New Zealand participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, rheumatologists from 15 national scientific committees selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 EULAR/ACR abstracts. Relevant studies were retrieved for data extraction and risk of bias assessment. Rheumatologists from Australia and New Zealand used the evidence to develop a set of national recommendations. These recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. The Oxford Levels of Evidence and Grade of Recommendation were applied to each recommendation., Results: The systematic reviews identified 49 242 references, from which 167 studies which met the pre-specified inclusion criteria. Combining this evidence with expert opinion led to the development of 10 final Australian and New Zealand recommendations. The recommendations relate to pain measurement, and the use of analgesic medications in patients with and without co-morbidities and during pregnancy and lactation. The recommendations reflect the clinical practice of the majority of the participating rheumatologists (mean level of agreement 7.24-9.65)., Conclusions: Ten Australian and New Zealand evidence-based recommendations regarding the management of pain by pharmacotherapy in adults with optimally treated IA were developed. They are supported by a large panel of rheumatologists, thus enhancing their utility in everyday clinical practice., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Musculoskeletal conditions are the leading contributors to disability burden globally and account for 27.4% of total disability burden in Australia. Timely research that addresses important questions relevant to consumers, clinicians and policymakers is critical for reducing the burden associated with these conditions. Clinical trials are particularly important for providing information about whether interventions are effective and safe. They are also needed to test strategies for reducing the sizeable delays in translating evidence into practice. A review of the current scope of musculoskeletal clinical trials in Australia found that National Health and Medical Research Council funding is disproportionally low compared with the burden of these conditions (averaging 5.8 new trials per year through the project grant scheme over the past 5 years, representing 0.8% of all project grants and funding, and 5% of NHMRC clinical trial funding). In the past 2 years, 128 Australian-initiated trials were registered in a trial registry, while about one in 20 randomised trials published in 37 leading general medical and musculoskeletal-specific journals was initiated in Australia. None were implementation trials. Relative to the burden of musculoskeletal conditions in Australia, investment in clinical trials is not ideal. While Australian musculoskeletal trialists are productive and internationally competitive, we may not be addressing the most critical issues. There is an urgent need for Australian researchers, clinicians, policymakers and consumers to work collaboratively to prioritise the most important questions, secure appropriate research funding, and undertake well designed trials to ensure we deliver best evidence-informed care and optimal outcomes for people with musculoskeletal conditions.

CLINICAL QUESTION Do the benefits of opioid analgesics outweigh the risks in patients with persistent pain due to rheumatoid arthritis? BOTTOM LINE Weak opioids (such as codeine, dextropropoxyphene, and tramadol) may be effective in the short-term management of rheumatoid arthritis pain, but adverse effects are common and may outweigh the benefits; alternative analgesics should be considered first.

Objectives: To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA)., Methods: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any antidepressants (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. A risk of bias assessment was performed using methods recommended by the Cochrane Collaboration., Results: Eight trials (652 participants) in patients with rheumatoid arthritis (RA) and 1 trial in patients with ankylosing spondylitis (100 participants) were included in this review. The majority of studies were published in the late 1980s in patients with active disease receiving minimal disease-modifying antirheumatic drug therapy. All trials evaluated tricyclic antidepressants (TCA) and 2 studies included a selective serotonin uptake inhibitor. Seven of the 9 trials had high risk of bias, 2 were unclear, and metaanalysis was not performed due to trial heterogeneity. RA trials with short-term outcome (< 1 week) found no significant benefit of amitriptyline 25 mg in combination with dextropropoxyphene (DXP) 65 mg over placebo, and inferiority of amitriptyline + DXP versus DXP 130 mg [mean difference (MD) 10.0, 95% CI 0.4 to 19.6]. There was conflicting evidence regarding medium (1-6 wks) or longer-term (> 6 wks) benefits on pain. One trial in depressed patients with RA showed no significant difference between amitriptyline and paroxetine given for 8 weeks (65% vs 56% much or very much improved; RR 1.2, 95% CI 0.9 to 1.5). One trial found that amitriptyline was no better than placebo in reducing pain in patients with active AS over 2 weeks (MD -0.2, 95% CI -1.2 to 0.8). From 5 trials, withdrawals due to adverse events were not significantly different from placebo. However, there were significantly more minor adverse events in patients receiving TCA compared with those receiving a placebo (RR 2.3, 95% CI 1.2 to 4.4). These included somnolence, dizziness, dry mouth, and nausea., Conclusion: Based upon 9 trials of high or unclear risk of bias, it is not possible to draw firm conclusions about the efficacy of TCA as analgesics for patients with IA. The use of these agents may be associated with adverse events that are generally mild and do not lead to cessation of treatment. High-quality trials are needed in this area.

Objective: To determine the efficacy and safety of opioid analgesics in inflammatory arthritis (IA)., Methods: We searched Medline, Embase, and Central to May 2010. Randomized controlled trials in adults with IA that compared opioids (administered via any route) to another intervention or placebo were included. Studies in the immediate postoperative setting were excluded. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events (AE). Categorical data were pooled using RevMan5 and reported as relative risks (RR) or odds ratios (OR) with 95% confidence intervals (95% CI)., Results: Eleven studies were included, all in patients with RA. The risk of bias of all studies was high. No study was longer than 6 weeks in duration and 4 studies used single doses of study drugs. Seven studies were between 1 and 6 weeks in duration and assessed 6 different oral opioids. Only 1 study investigated a strong opioid. Data could be pooled from 4 studies comparing weak opioids to placebo: there was no difference in withdrawals due to inadequate analgesia (RR 0.82, 95% CI 0.34, 2.01), but patient-reported global impression of change was superior with opioids (RR 1.44, 95% CI 1.03, 2.03). Opioids were more likely than placebo to cause AE (OR 3.90, 95% CI 2.31, 6.56). There was no difference between opioids and placebo in net efficacy after adjustment for AE., Conclusion: Based on 11 heterogeneous studies of short duration and high risk of bias, there is weak evidence that opioids are effective analgesics in RA. AE are common and may offset the benefits. The relative risks and benefits of opioids in IA beyond 6 weeks are unknown.

Objective: To determine the efficacy and safety of neuromodulators for pain management in patients with inflammatory arthritis., Methods: A Cochrane systematic review was performed as part of the 3e Initiative on pain management in inflammatory arthritis. We searched Medline, Embase, and Cochrane Central for studies to November 2010, and American College of Rheumatology/European League Against Rheumatism meeting abstracts published in 2008-2009. Studies were included if they were randomized or quasirandomized controlled trials that compared any neuromodulator (excluding cannabis) to another therapy (active or placebo, including nonpharmacological therapies) for pain in patients with RA, psoriatic arthritis, ankylosing spondylitis, or spondyloarthritis. Primary outcomes of interest were patient-reported pain relief of 30% or greater and withdrawals due to adverse events. Two authors independently extracted data and assessed methodological quality. A risk of bias assessment was performed using the methods recommended by the Cochrane Collaboration., Results: Three trials, all in RA and all at high risk of bias, were included in this review. Two placebo-controlled trials evaluated nefopam (52 participants) and one placebo-controlled trial evaluated topical capsaicin 0.025% (31 participants). Pooled analysis showed a significant reduction in pain levels favoring nefopam over placebo after 2 weeks [weighted mean difference -21.2, 95% CI -35.6 to -6.7; number needed to treat (NNT) 2, 95% CI 1.4 to 9.5]. However, nefopam was associated with significantly more adverse events (RR 4.1, 95% CI 1.6 to 10.7; number needed to harm 9, 95% CI 2 to 367), predominantly nausea and sweating. In one trial, capsaicin reduced pain more than placebo at 1 and 2 weeks (MD -23.8, 95% CI -44.8 to -2.8; NNT 3, 95% CI 2-47, and -34.4, 95% CI -54.7 to -14.14; NNT 2, 95% CI 1.4 to 6, respectively). Of those who received capsaicin, 44% developed burning at the site of application and 2% withdrew as a result., Conclusion: Based on 3 small trials, which were all at high risk of bias, there is weak evidence that nefopam and capsaicin are superior to placebo in reducing pain in patients with RA, but both are associated with a significant side effect profile. There are no available data for other types of IA or for newer agents such as gabapentin or pregabalin.

Objective: To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis (IA)., Methods: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any muscle relaxant (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data., Results: Six trials (126 participants) were included in this review. All trials were deemed to have a high risk of bias. Five crossover trials evaluated benzodiazepine; 4 assessed diazepam (n = 71), and one assessed triazolam (n = 15). The sixth trial, a parallel-group study, evaluated zopiclone (non-benzodiazepine, n = 40). No trial was longer than 2 weeks and 3 single-dose trials assessed outcomes at 24 hours only. Overall, the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo (at 24 hours, 1 week, or 2 weeks) or in addition to nonsteroidal antiiflammatory drugs (at 24 hours) on pain intensity, function, or quality of life. Data from 2 trials of longer than 24-hour duration (diazepam and zopiclone, n = 74) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo [number needed to harm (NNTH) 3, 95% CI 2 to 7]. These were predominantly central nervous system side effects including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11)., Conclusion: Based upon the currently available evidence in patients with IA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or 1 week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks. However, even short-term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

Objective: To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA)., Methods: A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice., Results: A total of 49,242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice., Conclusions: Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.

Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between reef shark abundance and human populations. We analyzed data from 1607 towed-diver surveys (>1 ha transects surveyed by observers towed behind a boat) conducted at 46 reefs in the central-western Pacific Ocean, reefs that included some of the world's most pristine coral reefs. Estimates of shark density from towed-diver surveys were substantially lower (<10%) than published estimates from surveys along small transects (<0.02 ha), which is not consistent with inverted biomass pyramids (predator biomass greater than prey biomass) reported by other researchers for pristine reefs. We examined the relation between the density of reef sharks observed in towed-diver surveys and human population in models that accounted for the influence of oceanic primary productivity, sea surface temperature, reef area, and reef physical complexity. We used these models to estimate the density of sharks in the absence of humans. Densities of gray reef sharks (Carcharhinus amblyrhynchos), whitetip reef sharks (Triaenodon obesus), and the group "all reef sharks" increased substantially as human population decreased and as primary productivity and minimum sea surface temperature (or reef area, which was highly correlated with temperature) increased. Simulated baseline densities of reef sharks under the absence of humans were 1.1-2.4/ha for the main Hawaiian Islands, 1.2-2.4/ha for inhabited islands of American Samoa, and 0.9-2.1/ha for inhabited islands in the Mariana Archipelago, which suggests that density of reef sharks has declined to 3-10% of baseline levels in these areas., (©2012 Society for Conservation Biology No claim to original US government works.)

Background: Pain management is a high priority for patients with rheumatoid arthritis (RA). Despite deficiencies in research data, neuromodulators have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain., Objectives: The aim of this review was to determine the efficacy and safety of neuromodulators in pain management in patients with RA. Neuromodulators included in this review were anticonvulsants (gabapentin, pregabalin, phenytoin, sodium valproate, lamotrigine, carbamazepine, levetiracetam, oxcarbazepine, tiagabine and topiramate), ketamine, bupropion, methylphenidate, nefopam, capsaicin and the cannabinoids., Search Methods: We performed a computer-assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44, 2010) and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 and 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conference abstracts and performed a handsearch of reference lists of articles., Selection Criteria: We included randomised controlled trials which compared any neuromodulator to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA that had at least one clinically relevant outcome measure., Data Collection and Analysis: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of a neuromodulator on pain, depression and function as well as their safety., Main Results: Four trials with high risk of bias were included in this review. Two trials evaluated oral nefopam (52 participants) and one trial each evaluated topical capsaicin (31 participants) and oromucosal cannabis (58 participants).The pooled analyses identified a significant reduction in pain levels favouring nefopam over placebo (weighted mean difference (WMD) -21.16, 95% CI -35.61 to -6.71; number needed to treat (NNT) 2, 95% CI 1.4 to 9.5) after two weeks. There were insufficient data to assess withdrawals due to adverse events. Nefopam was associated with significantly more adverse events (RR 4.11, 95% CI 1.58 to 10.69; NNTH 9, 95% CI 2 to 367), which were predominantly nausea and sweating.In a mixed population trial, qualitative analysis of patients with RA showed a significantly greater reduction in pain favouring topical capsaicin over placebo at one and two weeks (MD -23.80, 95% CI -44.81 to -2.79; NNT 3, 95% CI 2 to 47; MD -34.40, 95% CI -54.66 to -14.14; NNT 2, 95% CI 1.4 to 6 respectively). No separate safety data were available for patients with RA, however 44% of patients developed burning at the site of application and 2% withdrew because of this.One small, low quality trial assessed oromucosal cannabis against placebo and found a small, significant difference favouring cannabis in the verbal rating score 'pain at present' (MD -0.72, 95% CI -1.31 to -0.13) after five weeks. Patients receiving cannabis were significantly more likely to suffer an adverse event (risk ratio (RR) 1.82, 95% CI 1.10 to 3.00; NNTH 3, 95% CI 3 to 13). These were most commonly dizziness (26%), dry mouth (13%) and light headedness (10%)., Authors' Conclusions: There is currently weak evidence that oral nefopam, topical capsaicin and oromucosal cannabis are all superior to placebo in reducing pain in patients with RA. However, each agent is associated with a significant side effect profile. The confidence in our estimates is not strong given the difficulties with blinding, the small numbers of participants evaluated and the lack of adverse event data. In some patients, however, even a small degree of pain relief may be considered worthwhile. Until further research is available, given the relatively mild nature of the adverse events, capsaicin could be considered as an add-on therapy for patients with persistent local pain and inadequate response or intolerance to other treatments. Oral nefopam and oromucosal cannabis have more significant side effect profiles however and the potential harms seem to outweigh any modest benefit achieved.

Background: Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain., Objectives: The aim of this review was to determine the efficacy and safety of muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium)., Search Methods: We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles., Selection Criteria: We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome., Data Collection and Analysis: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of muscle relaxants on pain, depression, sleep and function, as well as their safety., Main Results: Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). , Authors' Conclusions: Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

Large-bodied reef fishes represent an economically and ecologically important segment of the coral reef fish assemblage. Many of these individuals supply the bulk of the reproductive output for their population and have a disproportionate effect on their environment (e.g. as apex predators or bioeroding herbivores). Large-bodied reef fishes also tend to be at greatest risk of overfishing, and their loss can result in a myriad of either cascading (direct) or indirect trophic and other effects. While many studies have investigated habitat characteristics affecting populations of small-bodied reef fishes, few have explored the relationship between large-bodied species and their environment. Here, we describe the distribution of the large-bodied reef fishes in the Mariana Archipelago with an emphasis on the environmental factors associated with their distribution. Of the factors considered in this study, a negative association with human population density showed the highest relative influence on the distribution of large-bodied reef fishes; however, depth, water temperature, and distance to deep water also were important. These findings provide new information on the ecology of large-bodied reef fishes can inform discussions concerning essential fish habitat and ecosystem-based management for these species and highlight important knowledge gaps worthy of additional research.

Background: Pain management is a high priority for patients with rheumatoid arthritis (RA). Antidepressants are sometimes used as adjuvant agents to enhance pain relief, help with sleep and reduce depression. Such antidepressants include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin noradrenaline reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). However, the prescription of antidepressants in this population remains controversial because of conflicting scientific evidence., Objectives: The aim of this review was to determine the efficacy and safety of antidepressants in pain management in patients with RA., Search Methods: We performed a computer assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter); MEDLINE (1950 to November Week 1, 2010); EMBASE (2010 Week 44); and PsycINFO (1806 to November Week 2, 2010). We also searched the 2008-2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of articles., Selection Criteria: We included randomised controlled trials (RCTs) which compared an antidepressant therapy to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA who had at least one clinically relevant outcome measure. Outcomes of interest were pain, adverse effects, function, sleep, depression and quality of life., Data Collection and Analysis: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. We conducted meta-analyses to examine the efficacy of antidepressants on pain, depression and function, as well as their safety., Main Results: We included eight RCTs (652 participants) in this review. All trials evaluated TCAs and two trials evaluated a SSRI as a comparator. Seven of the eight trials had high risk of bias. There was insufficient data for a number needed to treat for an additional beneficial outcome (NNTB) to be calculated for the primary outcome measure of pain. The qualitative analyses found no evidence of an effect of antidepressants on pain intensity or depression in the short-term (less than one week), and conflicting evidence of a medium- (one to six weeks) or long-term (more than six weeks) benefit. There were significantly more minor adverse events in patients receiving TCAs compared with those receiving a placebo (risk ratio (RR) 2.27, 95% confidence interval (CI) 1.17 to 4.42), but there was no significant increase in withdrawals due to an adverse event (RR 1.09, 95% CI 0.49 to 2.42)., Authors' Conclusions: There is currently insufficient evidence to support the routine prescription of antidepressants as analgesics in patients with RA as no reliable conclusions about their efficacy can be drawn from eight placebo RCTs. The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment. More high quality trials are needed in this area.

Background: Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled., Objectives: To assess the efficacy and safety of opioid analgesics for treating pain in patients with RA., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE for studies to May 2010. We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles., Selection Criteria: Studies were included if they were randomized or quasi-randomized controlled trials (RCTs or CCTs) which compared opioid therapy to another therapy (active or placebo) for pain in patients with RA. Outcomes of interest were pain, adverse effects, function and quality of life., Data Collection and Analysis: Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment., Main Results: Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions., Authors' Conclusions: There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids.

The systemic vasculitides are multisystem disorders characterised by the inflammation of blood vessels and tissue necrosis. Classified by the size of the vessels affected, the large vessel vasculitides include giant cell arteritis (GCA) and Takayasu's arteritis (TA). These are anatomically, epidemiologically and clinically distinct conditions. They are often associated with considerable morbidity and mortality. The classification of vasculitis has been an area of controversy for many years and current classification criteria remain suboptimal. Although intensive efforts are under way to improve them, a further understanding of the aetiology and pathogenesis of these diseases is required to develop more sensitive and specific diagnostic tests. These efforts, however, have been hampered by the low prevalence of these diseases. The establishment of national and international registries is encouraged to enhance valuable data collection. These are anatomically, epidemiologically and clinically distinct conditions. This article summarises the current classification systems for systemic vasculitis and their limitations. We also review the presently known epidemiology, risk factors and morbidity and mortality associated with GCA and TA., (2010. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to determine the neurophysiological effects of leflunomide on peripheral nerves in rheumatoid arthritis., Methods: We conducted a prospective cohort trial of 32 patients with rheumatoid arthritis with 16 patients receiving leflunomide treatment and 16 receiving other disease-modifying anti-rheumatic drug therapies. Clinical, laboratory and neurophysiological measurements were used to determine the presence of a peripheral neuropathy in these patients at study entry and then after a further 3 and 6 months., Results: Fifty-four per cent of the leflunomide group and 8% of the control group had an increase in their neuropathy symptom score 6 months into the study (P = 0.01). No correlation was found between the electrophysiological findings and the clinical symptoms. There was no significant difference between the two groups in upper and lower limb sensory and motor amplitudes and conduction velocities recorded at 3 and 6 months. One patient developed both clinical and neurophysiological evidence of a peripheral neuropathy 5 months into the study that improved after cessation of leflunomide therapy and cholestyramine washout., Conclusion: After 6 months of exposure we found that leflunomide was associated with an apparent increase in the clinical symptoms of peripheral neuropathy in patients with rheumatoid arthritis. These symptoms did not correlate with neurophysiological studies.

Cattle are considered to be a reservoir host of Escherichia coli O157:H7 and contaminated foods of bovine origin are important vehicles of human infection. In this study, the susceptibility of calves to experimental E. coli O157:H7 infection following low oral exposures was determined. Two of 17 calves exposed to very low (< 300 c.f.u.) doses, and 3 of 4 calves exposed to low (< 10,000 c.f.u.) doses, subsequently excreted the challenge strains in their faeces. All calves (n = 12) sharing isolation rooms with calves that excreted the challenge strain in their faeces similarly began faecal excretion of the same strains within 21 days or less. The identity between the challenge strains and the strains excreted in calf faeces was confirmed by restriction digestion electrophoretic patterns using pulsed field gel electrophoresis. Calves shed E. coli O157:H7 in their faeces after very low dose exposures at concentrations ranging from < 30 to > 10(7) c.f.u./g, and for durations similar to the values previously reported for calves challenged by larger doses. The susceptibility of calves to infection following very low exposures or direct contact with infected calves has important implications for programmes for pre-harvest control of this agent.

Background: Interleukin 8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. We hypothesize that IL-8 plays an important role in the cellular proliferation and angiogenesis seen in head and neck squamous cell carcinoma (HNSCC) and set out to identify its receptors, IL-8RA and IL-8RB., Methods: Immunohistochemical analysis was performed on specimens from 38 HNSCC patients with stage I to IV disease and control tissues., Results: All of cancer specimens demonstrated positive staining for IL-8RA. The IL-8RA staining of microvessel endothelial cells was seen in 51%. The IL-8RB pattern was similar to the IL-8RA pattern in that 97% of cancer sections demonstrated positive cancer cell staining, and 74% of the specimens demonstrated positive staining for microvessel endothelial cells., Conclusion: Our studies demonstrate that IL-8 receptors are expressed by cancer cells and microvessel endothelial cells in HNSCC, suggesting that IL-8 may act in an autocrine/paracrine fashion to stimulate cellular proliferation and angiogenesis.