Inhibitor regulation of tissue kallikrein activity in the synovial fluid of patients with rheumatoid athritis

Tissue kallikrein (TK) and 1-antitrypsin (AT)/TK complexes can be detected in SF from patients with RA if components of the fluids which interfere with the detection of TK are removed. 2-Macroglobulin (2-M) in SF was demonstrated to contain trapped proteases which were still active in amidase assays. Removal of 2-M from RA SF reduced their amidase activity. However, at least some of the remaining activity was due to TK because it was soya bean trypsin inhibitor resistant and trasylol sensitive and was partly removed by affinity chromatography on anti-TK sepharose. Removal of RF from the fluids reduced the values obtained for TK levels by ELISA. Addition of SF to human urinary kallikrein (HUK) considerably reduced the levels of TK detected suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of components of >300 kDa from SF markedly reduced the TK ELISA inhibitory activity and increased the values for both the TK and l-AT/TK levels in fluids as measured by ELISA. It is considered this novel inhibitor does not bind to the active site of TK but rather binds to the site reactive with anti-TK antibodies

Review of 99 self-report measures for assessing well-being in adults: exploring dimensions of well-being and developments over time

This is the final version. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVE: Investigators within many disciplines are using measures of well-being, but it is not always clear what they are measuring, or which instruments may best meet their objectives. The aims of this review were to: systematically identify well-being instruments, explore the variety of well-being dimensions within instruments and describe how the production of instruments has developed over time. DESIGN: Systematic searches, thematic analysis and narrative synthesis were undertaken. DATA SOURCES: MEDLINE, EMBASE, EconLit, PsycINFO, Cochrane Library and CINAHL from 1993 to 2014 complemented by web searches and expert consultations through 2015. ELIGIBILITY CRITERIA: Instruments were selected for review if they were designed for adults (≥18 years old), generic (ie, non-disease or context specific) and available in an English version. RESULTS: A total of 99 measures of well-being were included, and 196 dimensions of well-being were identified within them. Dimensions clustered around 6 key thematic domains: mental well-being, social well-being, physical well-being, spiritual well-being, activities and functioning, and personal circumstances. Authors were rarely explicit about how existing theories had influenced the design of their tools; however, the 2 most referenced theories were Diener's model of subjective well-being and the WHO definition of health. The period between 1990 and 1999 produced the greatest number of newly developed well-being instruments (n=27). An illustration of the dimensions identified and the instruments that measure them is provided within a thematic framework of well-being. CONCLUSIONS: This review provides researchers with an organised toolkit of instruments, dimensions and an accompanying glossary. The striking variability between instruments supports the need to pay close attention to what is being assessed under the umbrella of 'well-being' measurement.This research was supported by a University of Exeter Medical School PhD Studentship

Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National Joint Registry of England and Wales and hospital episode statistics

Objective To determine whether use of metal-on-metal bearing surfaces is associated with an increased risk of a diagnosis of cancer in the early years after total hip replacement and specifically with an increase in malignant melanoma and haematological, prostate, and renal tract cancers

MOBILE and the provision of total joint replacement

Modern joint replacements have been available for 45 years, but we still do not have clear indications for these interventions, and we do not know how to optimize the outcome for patients who agree to have them done. The MOBILE programme has been investigating these issues in relation to primary total hip and knee joint replacements, using mixed methods research

The Influence of Arthritis in Other Major Joints and the Spine on the One-Year Outcome of Total Hip Replacement:A Prospective, Multicenter Cohort Study (EUROHIP) Measuring the Influence of Musculoskeletal Morbidity

Background Whilst arthritis in other affected joints and back pain is known to lead to worse outcomes following total hip replacement surgery, these risk factors have not previously been operationalized as a musculoskeletal morbidity profile. The aim of this study was to measure the influence of other joints and spine (as grades of musculoskeletal morbidity) on the 1-year outcome of primary total hip replacement. Methods The European Collaborative Database of Cost and Practice Patterns of Total Hip Replacement study consists of 1,327 patients receiving primary THR for osteoarthritis across 20 European orthopedic centers. The primary outcome was the responder rate for THR at 12-months as measured by the relative effect per patient (REPP score), calculated for each patient using the total WOMAC score. The primary predictor of interest was combinations of arthritis of large joints and spine grouped into four musculoskeletal morbidity (MSM) grades: 1 (single-joint), 2 (multi-joints), 3 (single-joint and spine), 4 (multi-joints and spine). Confounders adjusted for were: age, sex, body mass index, living alone, years of hip pain, ASA grade, anxiety/depression, pre-operative WOMAC subscales. Results 845 patients were included for this analysis with complete 12-month follow-up WOMAC scores. The mean age was 65.7 years and 55.2% were female. Increasing MSM grade was associated with worse outcomes of surgery, where the proportion of patients responding to THR were: 254 (92.4%) MSM grade 1, 272 (87.2%) MSM grade 2, 46 (80.7%) MSM grade 3, 142 (74.4%) MSM grade 4. This was confirmed in adjusted logistic regression models: MSM grade 4 vs. 1 relative risk ratio (RRR) 0.82 95% confidence interval (CI) (0.75, 0.90); MSM grade 3 vs. 1 OR 0.87 95%CI (0.77, 0.99); MSM grade 2 vs. 1 OR 0.95 95%CI (0.89, 1.00). Conclusions Other joints and spine measured as musculoskeletal morbidity have a strong influence on the 1-year outcome after THR. The effect size was large in comparison to other risk factors. Even so, the majority of patients in MSM grade 4 can still profit from surgery (>75% response to surgery)

The power of invalidating communication: Receiving invalidating feedback predicts threat-related emotional, physiological, and social responses

© 2016 Guilford Publications, Inc. Previous studies have found that communicating acceptance and understanding (validation) enhances the recipient's psychological and physiological wellbeing compared with receiving nonunderstanding feedback (invalidation). Yet, such studies have not established whether it is validation or absence of invalidation that is beneficial. This study examined the social, physiological, and emotional effects of validating and invalidating feedback in more detail, by employing a control group. Ninety healthy volunteers were randomly allocated to receive validating, invalidating, or no feedback during a series of stressor tasks. Self-report ratings, psychophysiological measurements and social engagement behaviors were recorded. While there were no significant differences between validated and control participants, invalidated participants showed increased physiological and psychological arousal on several measures and reduced social engagement behaviors compared with the other two groups. the relevance of these findings for understanding adverse effects of invalidation during clinical interactions is discussed

Evaluating elbow osteoarthritis within the prehistoric Tiwanaku state using generalized estimating equations (GEE).

OBJECTIVES:Studies of osteoarthritis (OA) in human skeletal remains can come with scalar problems. If OA measurement is noted as present or absent in one joint, like the elbow, results may not identify specific articular pathology data and the sample size may be insufficient to address research questions. If calculated on a per data point basis (i.e., each articular surface within a joint), results may prove too data heavy to comprehensively understand arthritic changes, or one individual with multiple positive scores may skew results and violate the data independence required for statistical tests. The objective of this article is to show that the statistical methodology Generalized Estimating Equations (GEE) can solve scalar issues in bioarchaeological studies. MATERIALS AND METHODS:Using GEE, a population-averaged statistical model, 1,195 adults from the core and one colony of the prehistoric Tiwanaku state (AD 500-1,100) were evaluated bilaterally for OA on the seven articular surfaces of the elbow joint. RESULTS:GEE linked the articular surfaces within each individual specimen, permitting the largest possible unbiased dataset, and showed significant differences between core and colony Tiwanaku peoples in the overall elbow joint, while also pinpointing specific articular surfaces with OA. Data groupings by sex and age at death also demonstrated significant variation. A pattern of elbow rotation noted for core Tiwanaku people may indicate a specific pattern of movement. DISCUSSION:GEE is effective and should be encouraged in bioarchaeological studies as a way to address scalar issues and to retain all pathology information

Clinical predictors of elective total joint replacement in persons with end-stage knee osteoarthritis

Abstract Background Arthritis is a leading cause of disability in the United States. Total knee arthroplasty (TKA) has become the gold standard to manage the pain and disability associated with knee osteoarthritis (OA). Although more than 400 000 primary TKA surgeries are performed each year in the United States, not all individuals with knee OA elect to undergo the procedure. No clear consensus exists on criteria to determine who should undergo TKA. The purpose of this study was to determine which clinical factors will predict the decision to undergo TKA in individuals with end-stage knee OA. Knowledge of these factors will aid in clinical decision making for the timing of TKA. Methods Functional data from one hundred twenty persons with end-stage knee OA were obtained through a database. All of the individuals complained of knee pain during daily activities and had radiographic evidence of OA. Functional and clinical tests, collectively referred to as the Delaware Osteoarthritis Profile, were completed by a physical therapist. This profile consisted of measuring height, weight, quadriceps strength and active knee range of motion, while functional mobility was assessed using the Timed Up and Go (TUG) test and the Stair Climbing Task (SCT). Self-perceived functional ability was measured using the activities of daily living subscale of the Knee Outcome Survey (KOS-ADLS). A logistic regression model was used to identify variables predictive of TKA use. Results Forty subjects (33%) underwent TKA within two years of evaluation. These subjects were significantly older and had significantly slower TUG and SCT times (p 2 = 0.403). Conclusions Younger patients with full knee ROM who have a higher self-perception of function are less likely to undergo TKA. Physicians and clinicians should be aware that potentially modifiable factors, such as knee ROM can be addressed to potentially postpone the need for TKA.</p

(Re)acting Medicine: applying theatre in order to develop a whole-systems approach to understanding the healing response.

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Research in Drama Education: The Journal of Applied Theatre and Performance on 30/09/2014, available online: http://www.tandfonline.com/10.1080/13569783.2014.928007UK health and care provision is in crisis. Dominant practices, ideologies and infrastructure need to change. Our research team is investigating how performance-led research and creative practice is able to positively shape that change. Presently biomedicine holds the power; its reductionist research approach and acute medical model dominate. Neither are well-equipped to engage with increasing non-communicable, long-term, multi-issue, chronic ill-health. We believe that creative practitioners should be using their own well-established approaches to trouble this dominant paradigm to both form and inform the future of healing provision and wellbeing creation. Our transdisciplinary team (drama and medicine) is developing a methodology that is rooted in productive difference; an evolving synergy between two cultural and intellectual traditions with significant divergences in their world-view, perceptions, approaches and training methods. This commonality is underpinned by four assumptions that; (1) human-to-human interactions matter, (2) context matters, (3) the whole person and their community matters and (4) interpretation matters. Initially, we are using this methodology to investigate the fundamental human-to-human interaction of a person seeking healing (a healee) with a healer: we believe that this interaction enables the Healing Response - the intrinsic ability of the human organism to self-heal and regain homeostasis. In this paper we reflect on the project’s early stages