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

Doctors' understanding of individualisation of drug treatments: a qualitative interview study

addresses: University of Exeter Medical School, Institute of Health Services Research, Exeter, UK.notes: PMCID: PMC3657639To explore doctors' understanding of individualisation of drug treatments, and identify the methods used to achieve individualisation

Individualisation of drug treatments for patients with long-term conditions: a review of concepts.

Journal ArticleOBJECTIVES: Patients and policy makers advocate that drug treatments should be individualised. However, the term is used in a variety of ways. We set out to identify the range of related terminology and concepts in the general field of individualisation, map out the relationships between these concepts and explore how patients' perspectives are considered. DESIGN: We consulted members of an established patient and public involvement group about their experience of medicine taking for long-term conditions and their ideas about individualisation. We then conducted a scoping review of the literature to explore how terms surrounding individualisation of drug treatment are used and defined in the literature, and to explore the extent to which patients' perspectives are represented, with a view to informing future recommendations as to how individualisation can be operationalised. METHODS: We identified relevant literature using a range of search strategies. Two researchers independently extracted definitions of terms using a template. Inductive and deductive methods were used to explore the data. RESULTS: Definitions were categorised according to the following themes: medical management; pharmacogenetics, the patient's perspective; interactions between the healthcare provider and patient and management of long-term conditions. CONCLUSIONS: Within the literature reviewed, the involvement of patients in the ongoing management of drug treatment was largely absent. We propose the use of a new term 'mutually agreed tailoring' (MAT). This describes the ongoing pharmacological management of conditions that incorporates patients' specific needs, experiences and existing strategies for using their medications, and the professionals' clinical judgement. This usually includes patients monitoring their symptoms and, with the support of the professional, making appropriate product, dose or timing adjustments as necessary. Our previous work suggests that many patients and doctors are successfully practising MAT, so we suggest that a formal description may facilitate wider utilisation of strategies that will improve patient outcomes.NIHR - CLAHR

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

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

Population requirement for primary knee replacement surgery: a cross‐sectional study

Objectives. To determine the population requirement for total knee replacement (TKR) in England Methods. Population‐based study using an age/sex‐stratified random sample of 28 080 individuals aged 35 yr and over. Incident disease was estimated from prevalence by statistical modelling. The New Zealand priority criteria for major joint replacement were used for case selection. Results. Patients with knee disease were less likely than those with equally severe hip disease to have been referred to a specialist, to have consulted an orthopaedic surgeon or to be on a waiting list for joint replacement. The estimated annual requirement of TKRs in England, based on New Zealand Scores alone, was 55 800 (95% CI 40 700-70 900), contrasting sharply with an annual provision of 29 300 actually observed. However, in contrast to previously reported hip replacement data, when patient willingness to undergo surgery was considered, this estimate decreased considerably. Conclusions. There appears to be an underprovision of TKR in England. This may be due in part to differences in perception of disease severity and likely response to surgery between patients and general practitioners on one hand, and rheumatologists and orthopaedic surgeons on the othe

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.

addresses: Musculosketal Research Unit, School of Clinical Sciences, University of Bristol, Avon Orthopaedic Centre, Bristol BS10 5NB, UK. [email protected]: PMCID: PMC3318111types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2012 by the BMJ Publishing Group Ltd. This articles was first published in: BMJ, 2012, Vol. 344, pp. e2383 -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