THE RELATIONSHIP OF TIBIAL BONE PERFUSION TO PAIN IN KNEE OSTEOARTHRITIS.

Objective To confirm altered perfusion within tibial bone marrow lesions (BMLs) and improve our understanding on the relationship between BMLs and pain in knee osteoarthritis (OA). Methods Participants with moderate to severe knee OA were recruited and pain was assessed using the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were identified and graded on magnetic resonance imaging (MRI) proton density-weighted (PDW) fat suppressed images. A pharmacokinetic model was used to analyze perfusion parameters on dynamic contrast enhanced (DCE) MRI which represent transfer rates in and out of the BMLs. The relation between perfusion and pain was evaluated using multivariable linear regression after adjustment for BML grade, age, gender and body mass index (BMI). Results There were 37 participants (mean age 64.9 years, range 46–86) with radiographic Kellgren and Lawrence grades of 3 and 4 in the study knee; 75.6% had BMLs that were classified grades 1 and 2. The mean WOMAC pain score was 10.3 (0–20 scale). There was a significant correlation between BML Kel (rate of contrast elimination) and BML grade (P = 0.001 univariate, P = 0.002 multivariate analyses), although we did not demonstrate any significant multivariate association between BML perfusion and pain. We also found an inverse relationship between pain at sleep and BML grade (P < 0.05). Conclusions The absence of any significant association between bone perfusion and pain implies that the relationship of tibial BMLs to pain in OA is still incompletely understood. BMLs are just one component of the whole knee joint and are formed from various causes, all of which interact and collectively contribute to the genesis of pain in OA

THE RELATIONSHIP OF TIBIAL BONE PERFUSION TO PAIN IN KNEE OSTEOARTHRITIS.

Objective To confirm altered perfusion within tibial bone marrow lesions (BMLs) and improve our understanding on the relationship between BMLs and pain in knee osteoarthritis (OA). Methods Participants with moderate to severe knee OA were recruited and pain was assessed using the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were identified and graded on magnetic resonance imaging (MRI) proton density-weighted (PDW) fat suppressed images. A pharmacokinetic model was used to analyze perfusion parameters on dynamic contrast enhanced (DCE) MRI which represent transfer rates in and out of the BMLs. The relation between perfusion and pain was evaluated using multivariable linear regression after adjustment for BML grade, age, gender and body mass index (BMI). Results There were 37 participants (mean age 64.9 years, range 46–86) with radiographic Kellgren and Lawrence grades of 3 and 4 in the study knee; 75.6% had BMLs that were classified grades 1 and 2. The mean WOMAC pain score was 10.3 (0–20 scale). There was a significant correlation between BML Kel (rate of contrast elimination) and BML grade (P = 0.001 univariate, P = 0.002 multivariate analyses), although we did not demonstrate any significant multivariate association between BML perfusion and pain. We also found an inverse relationship between pain at sleep and BML grade (P < 0.05). Conclusions The absence of any significant association between bone perfusion and pain implies that the relationship of tibial BMLs to pain in OA is still incompletely understood. BMLs are just one component of the whole knee joint and are formed from various causes, all of which interact and collectively contribute to the genesis of pain in OA

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international group working together to develop a core outcome set (COS) for clinical trials in eczema (synonymous with atopic eczema and atopic dermatitis). HOME is coordinated from the Centre of Evidence Based Dermatology, University of Nottingham, U.K. Participation in HOME is open to anyone with an interest in outcomes for eczema. A COS is the agreed upon minimum set of instruments that should be included in all clinical trials for a particular condition. Use of a COS does not preclude using other instruments; other domains and instruments can also be included to meet the specific requirements of individual trials. COS initiatives are active across many fields of medicine and should enable better synthesis of trial data and reduce selective outcome reporting bias. The HOME initiative follows the best current guidance on developing a COS. Four core domains have been identified: clinician-reported signs; patient-reported symptoms; quality of life; and long-term control. The core outcome measurement instruments for clinician-reported signs and patient-reported symptoms have been established: the Eczema Area and Severity Index (EASI) for measuring clinician reported signs was agreed on at the HOME III meeting, and the Patient-Oriented Eczema Measure (POEM) was chosen to measure patient-reported symptoms at the HOME IV meeting. This is a report from the fifth consensus meeting of the HOME initiative (HOME V), which was held on 12–14 June 2017 in Nantes, France. The local organizers were Sebastien Barbarot and Jean-Francois Stalder of Nantes University Hospital, France

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms

Use of routine hospital morbidity data together with weight and height of patients to predict in-hospital complications following total joint replacement

Extent: 8p. The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1472-6963/12/380BackgroundRoutinely collected data such as hospital morbidity data (HMD) are increasingly used in studying clinical outcomes among patients undergoing total joint replacement (TJR). These data are readily available and cover large populations. However, since these data were not originally collected for the purpose of health research, a rigorous assessment of their quality is required. We assessed the accuracy of the diagnosis of obesity in HMD and evaluated whether the augmentation of HMD with actual weight and height of patients could improve their ability to predict major in-hospital complications following total joint replacement in men.MethodsThe electronic records of 857 participants in the Health In Men Study (HIMS) who had had TJR were linked with Western Australia HMD. HMD-recorded diagnosis of obesity was validated using the actual weight and height obtained from HIMS. In-hospital major complications were modelled using multivariable logistic regressions that either included the actual weight and height or HMD-recorded obesity. Model discrimination was calculated using area under ROC curve.ResultsThe HMD failed to detect 70% of the obese patients. Only 64 patients (7.5%) were recorded in HMD as obese although 216 (25%) were obese [BMI: ≥30kg/m2] (sensitivity: 0.2, positive predictive value: 0.7). Overall, 174 patients (20%) developed an in-hospital major complication which was significantly higher in the overweight and obese comparing with patients with normal weight. HMD-recorded obesity was not independently associated with major complications, whereas a dose-response relationship between weight and these complications was observed (P=0.004). Using the actual weight and height of the participants instead of HMD-recorded diagnosis of obesity improved model discrimination by 9%, with areas under ROC curve of: 0.69, 95% CI: 0.64-0.73 for the model with HMD-recorded obesity compared with 0.75, 95% CI: 0.70-0.79 for the model with actual weight and height, PConclusionBody weight is an important risk factor for in-hospital complications in patients undergoing TJR. HMD systems do not include weight and height as variables whose recording is mandatory. Augmenting HMD with patients' weight and height may improve prediction of major complications following TJR. Our study suggests making these variables mandatory in any hospital morbidity data system.George Mnatzaganian, Philip Ryan, Paul E Norman, David C Davidson and Janet E Hille

Smoking and primary total hip or knee replacement due to osteoarthritis in 54,288 elderly men and women

BACKGROUND The reported association of smoking with risk of undergoing a total joint replacement (TJR) due to osteoarthritis (OA) is not consistent. We evaluated the independent association between smoking and primary TJR in a large cohort. METHODS The electronic records of 54,288 men and women, who were initially recruited for the Second Australian National Blood Pressure study, were linked to the Australian Orthopaedic Association National Joint Replacement Registry to detect total hip replacement (THR) or total knee replacement (TKR) due to osteoarthritis. Competing risk regressions that accounted for the competing risk of death estimated the subhazard ratios for TJR. One-way and probabilistic sensitivity analyses were undertaken to represent uncertainty in the classification of smoking exposure and socioeconomic disadvantage scores. RESULTS An independent inverse association was found between smoking and risk of THR and TKR observed in both men and women. Compared to non-smokers, male and female smokers were respectively 40% and 30% less likely to undergo a TJR. This significant association persisted after controlling for age, co-morbidities, body mass index (BMI), physical exercise, and socioeconomic disadvantage. The overweight and obese were significantly more likely to undergo TJR compared to those with normal weight. A dose–response relationship between BMI and TJR was observed (P < 0.001). Socioeconomic status was not independently associated with risk of either THR or TKR. CONCLUSION The strengths of the inverse association between smoking and TJR, the temporal relationship of the association, together with the consistency in the findings warrant further investigation about the role of smoking in the pathogenesis of osteoarthritis causing TJR.George Mnatzaganian, Philip Ryan, Christopher M Reid, David C Davidson and Janet E Hille

Periprosthetic osteolysis after total hip replacement: molecular pathology and clinical management

Periprosthetic osteolysis is a serious complication of total hip replacement (THR) in the medium to long term. Although often asymptomatic, osteolysis can lead to prosthesis loosening and periprosthetic fracture. These complications cause significant morbidity and require complex revision surgery. Here, we review advances in our understanding of the cell and tissue response to particles produced by wear of the articular and non-articular surfaces of prostheses. We discuss the molecular and cellular regulators of osteoclast formation and bone resorptive activity, a better understanding of which may lead to pharmacological treatments for periprosthetic osteolysis. We describe the development of imaging techniques for the detection and measurement of osteolysis around THR prostheses, which enable improved clinical management of patients, provide a means of evaluating outcomes of non-surgical treatments for periprosthetic osteolysis, and assist in pre-operative planning for revision surgery. Finally, there have been advances in the materials used for bearing surfaces to minimise wear, and we review the literature regarding the performance of these new materials to date.Donald W. Howie, Susan D. Neale, David R. Haynes, Oksana T. Holubowycz, Margaret A. McGee, Lucian B. Solomon, Stuart A. Callary, Gerald J. Atkins, David M. Findla

Fast estimation of plant growth dynamics using deep neural networks

BackgroundIn recent years, there has been an increase of interest in plant behaviour as represented by growth-driven responses. These are generally classified into nastic (internally driven) and tropic (environmentally driven) movements. Nastic movements include circumnutations, a circular movement of plant organs commonly associated with search and exploration, while tropisms refer to the directed growth of plant organs toward or away from environmental stimuli, such as light and gravity. Tracking these movements is therefore fundamental for the study of plant behaviour. Convolutional neural networks, as used for human and animal pose estimation, offer an interesting avenue for plant tracking. Here we adopted the Social LEAP Estimates Animal Poses (SLEAP) framework for plant tracking. We evaluated it on time-lapse videos of cases spanning a variety of parameters, such as: (i) organ types and imaging angles (e.g., top-view crown leaves vs. side-view shoots and roots), (ii) lighting conditions (full spectrum vs. IR), (iii) plant morphologies and scales (100 μm-scale Arabidopsis seedlings vs. cm-scale sunflowers and beans), and (iv) movement types (circumnutations, tropisms and twining).ResultsOverall, we found SLEAP to be accurate in tracking side views of shoots and roots, requiring only a low number of user-labelled frames for training. Top views of plant crowns made up of multiple leaves were found to be more challenging, due to the changing 2D morphology of leaves, and the occlusions of overlapping leaves. This required a larger number of labelled frames, and the choice of labelling “skeleton” had great impact on prediction accuracy, i.e., a more complex skeleton with fewer individuals (tracking individual plants) provided better results than a simpler skeleton with more individuals (tracking individual leaves).ConclusionsIn all, these results suggest SLEAP is a robust and versatile tool for high-throughput automated tracking of plants, presenting a new avenue for research focusing on plant dynamics.publishe