Rest Pain and Movement-Evoked Pain as Unique Constructs in Hip and Knee Replacements

OBJECTIVE: There is limited information about the extent to which the association between preoperative and chronic postoperative pain is mediated via pain‐on‐movement or pain‐at‐rest. We explored these associations in patients undergoing total hip replacement (THR) and total knee replacement (TKR). METHODS: A total of 322 and 316 patients receiving THR and TKR, respectively, were recruited into a single‐center UK cohort (Arthroplasty Pain Experience) study. Preoperative, acute postoperative, and 12‐month pain severity was measured using self‐reported pain instruments. The association between preoperative/acute pain and chronic postoperative pain was investigated using structural equation modeling (SEM). RESULTS: Patients with high levels of preoperative pain were more likely to report chronic pain after THR (β = 0.195, P = 0.02) and TKR (β = 0.749, P < 0.0001). Acute postoperative pain‐on‐movement was not associated with chronic pain after TKR or THR after adjusting for preoperative pain; however, acute pain‐at‐rest was associated with chronic pain after THR (β = 0.20, P < 0.0002) but not TKR after adjusting for preoperative pain. Analysis of pain‐at‐rest and pain‐on‐movement highlighted differences between THR and TKR patients. Chronic pain‐at‐rest after THR was weakly associated with pain‐at‐rest during the preoperative (β = 0.11, P = 0.068) and acute postoperative period (β = 0.21, P < 0.0001). In contrast, chronic pain‐on‐movement after TKR was strongly associated with the severity of pain‐on‐movement during the preoperative period (β = 0.51, P = 0.001). CONCLUSION: SEM illustrated the different patterns of association between measures of pain over time in patients undergoing THR and TKR for osteoarthritis. These findings highlight the importance of future work that explores the mechanisms underlying pain‐on‐movement and pain‐at‐rest

Application of biomimetic HPLC to estimate lipophilicity, protein and phospholipid binding of potential peptide therapeutics

Peptide therapeutics are new modalities offering several challenges to drug discovery. They are generally less stable and permeable in vivo. The characterization of their lipophilicity cannot be carried out using the traditional in silico or wet octanol/water partition coefficients. The prediction of their in vivo distribution and permeability is also challenging. In this paper, it is demonstrated that the biomimetic properties such as lipophilicity, protein and phospholipid binding can be easily assessed by HPLC using chemically bonded protein and immobilized artificial membrane (IAM) stationary phases. The obtained properties for a set of potential therapeutic peptides with 3 to 33 amino acids have been analysed and it was found that similar characteristics of the properties could be observed as for small molecule drugs. The albumin binding showed correlation with their measured lipophilicity on the C-18 stationary phase with acidic peptides showing stronger than expected albumin binding. The (IAM) chromatography revealed peptide membrane affinity, which was stronger for positively charged peptides (containing arginine) and showed correlation to the alpha-1-acid glycoprotein (AGP) binding, which was also stronger for positively charged compounds. The in vivo volume of distribution and drug efficiency of the peptides have been estimated using the models developed for small molecules. One of the candidate linear peptides has been assessed in various cellular and in vivo assays and the results have confirmed the estimated cell partition and brain to plasma ratio. It can be demonstrated, that up to 21 amino acids, the peaks of the peptides obtained on the protein phase were symmetrical and narrow. The interaction of larger peptides with the protein stationary phases resulted in wide peaks showing multiple equilibrium processes with slow kinetics during chromatography. The larger peptides showed narrow and symmetrical peaks on the IAM column enabling the quantification of peptide - cell membrane interactions

A new daily observational record from Grytviken, South Georgia: exploring 20th century extremes in the South Atlantic

Although recent work has highlighted a host of significant late 20th century environmental changes across the mid to high latitudes of the Southern Hemisphere, the sparse nature of observational records limits our ability to place these changes in the context of long-term (multi-decadal and centennial) variability. Historical records from sub-Antarctic islands offer considerable potential for developing highly resolved records of change. In 1905, a whaling and meteorological station was established at Grytviken on sub-Antarctic South Georgia in the South Atlantic (54°S, 36°W) providing near-continuous daily observations through to present day. Here we report a new, daily observational record of temperature and precipitation from Grytviken, which we compare to regional datasets and historical reanalysis (Twentieth Century Reanalysis; 20CR version 2c). We find a shift towards increasingly warmer daytime extremes commencing from the mid-20th century and accompanied by warmer night-time temperatures, with an average rate of temperature rise of 0.13°C per decade over the period 1907-2016 (p<0.0001). Analysis of these data, and reanalysis products, suggest a change of particular synoptic conditions across the mid to high-latitudes since the mid-20th century, characterised by stronger westerly airflow and associated warm föhn winds across South Georgia. This rapid rate of warming and associated declining habitat suitability has substantial negative implications for biodiversity levels and survival of key marine biota in the region

Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement:The APEX randomised controlled trials

Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: −0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR

PTF10fqs: A Luminous Red Nova in the Spiral Galaxy Messier 99

The Palomar Transient Factory (PTF) is systematically charting the optical transient and variable sky. A primary science driver of PTF is building a complete inventory of transients in the local Universe (distance less than 200 Mpc). Here, we report the discovery of PTF10fqs, a transient in the luminosity "gap" between novae and supernovae. Located on a spiral arm of Messier 99, PTF 10fqs has a peak luminosity of Mr = -12.3, red color (g-r = 1.0) and is slowly evolving (decayed by 1 mag in 68 days). It has a spectrum dominated by intermediate-width H (930 km/s) and narrow calcium emission lines. The explosion signature (the light curve and spectra) is overall similar to thatof M85OT2006-1, SN2008S, and NGC300OT. The origin of these events is shrouded in mystery and controversy (and in some cases, in dust). PTF10fqs shows some evidence of a broad feature (around 8600A) that may suggest very large velocities (10,000 km/s) in this explosion. Ongoing surveys can be expected to find a few such events per year. Sensitive spectroscopy, infrared monitoring and statistics (e.g. disk versus bulge) will eventually make it possible for astronomers to unravel the nature of these mysterious explosions.Comment: 12 pages, 12 figures, Replaced with published versio

Report from the second cytomegalovirus and immunosenescence workshop.

The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p &amp;lt; 0.001). Lesion volume (Spearman’s rho rs= 0.38, p &amp;lt; 0.001) and g-ratio (rs= 0.24 p &amp;lt; 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p &amp;lt; 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

The effect of local anaesthetic wound infiltration on chronic pain after lower limb joint replacement: A protocol for a double-blind randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA.</p> <p>Methods</p> <p>300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals.</p> <p>Discussion</p> <p>Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN96095682">ISRCTN96095682</a></p