Temporal trends in comorbidity in adult elective hip and knee arthroplasty patients in England : a national population-based cohort study from the National Joint Registry.

AIMS: Our main aim was to describe the trend in the comorbidities of patients undergoing elective total hip arthroplasties (THAs) and knee arthroplasties (KAs) between 1 January 2005 and 31 December 2018 in England. METHODS: We combined data from the National Joint Registry (NJR) on primary elective hip and knee arthroplasties performed between 2005 and 2018 with pre-existing conditions recorded at the time of their primary operation from Hospital Episodes Statistics. We described the temporal trend in the number of comorbidities identified using the Charlson Comorbidity Index, and how this varied by age, sex, American Society of Anesthesiologists (ASA) grade, index of multiple deprivation, and type of KA. RESULTS: We included 696,504 and 833,745 elective primary THAs and KAs respectively, performed for any indication. Between 2005 and 2018, the proportion of elective THA and KA patients with one or more comorbidity at the time of their operation increased substantially (THA: 20% to 38%, KA: 22% to 41%). This was driven by increases in four conditions: chronic obstructive pulmonary disease (COPD) (2018: ~17%), diabetes without complications (2018: THA 10%, KA 14%), myocardial infarction (2018: 4%), and renal disease (2018: ~8%). Notably, renal disease prevalence increased from < 1% in 2005 to ~8% in 2018. CONCLUSION: Between 2005 and 2018 there were significant changes in the number of comorbidities recorded in patients having elective primary THAs and KAs. Renal disease is now one of the most prevalent comorbidities in this patient population. Future research should explore whether this comorbidity trend has increased the burden on other medical specialities to optimize these patients before surgery and to provide additional postoperative care.Cite this article: Bone Joint J 2022;104-B(9):1052-1059.

Review: More effective linkages between science and policy are needed to minimize the negative environmental impacts of livestock production.

Animals form an integral part of our planetary ecosystem but balance is critical to effective ecosystem functioning as demand for livestock products has increased, greater numbers of domesticated livestock have created an imbalance and hence had a negative impact on a number of ecosystem services which means that life as we know it will become unsustainable. Policies and technology advances have helped to manage the impact but more needs to be done. The aim of this paper is to highlight ways in which better knowledge of animal science, and other disciplines, can both harness technology and inform policy to work towards a sustainable balance between livestock and the environment. Effective policies require simple, quantifiable indicators against which to set targets and monitor progress. Indicators are clear for water pollution, but more complex for biodiversity. Hence, more progress has been made with the former. It is not yet possible to measure the impacts of changes in livestock management on greenhouse gas emissions per se at a farm level and progress has been slower, although new technologies are emerging. With respect to land use, the simple indicator of area has been used, but total area is oversimplistic. Our analysis of land suitability and use highlights a relatively overlooked role of livestock in acting as a 'buffer' to use by-products and grains which do not meet the standards for processing by industry during years of inclement weather, which in the past has provided an 'insurance policy' for farmers. Since extreme weather events are increasing in frequency with climate change, this role for livestock may be more important in future. The conclusions of the review with respect to strengthening the links between research and policy are i) to encourage animal scientists to identify the relevant environmental indicators, work with the cutting edge experts developing technologies to measure these cost-effectively and across a range of relevant livestock systems and ii) to work with the feed industry to optimize diets not just in terms of least cost financially but also least 'cost' in terms of global carbon flux and engage in dialogue with the food industry and policy makers on regulations for grain quality.

Information and Decoherence in a Muon-Fluorine Coupled System.

The unitary evolution of a quantum system preserves its coherence, but interactions between the system and its environment result in decoherence, a process in which the quantum information stored in the system becomes degraded. A spin-polarized positively charged muon implanted in a fluoride crystal realizes such a coherent quantum system, and the entanglement of muon and nearest-neighbor fluorine nuclear spins gives rise to an oscillatory time dependence of the muon polarization that can be detected and measured. Here we show that the decohering effect of more distant nuclear spins can be modelled quantitatively, allowing a very detailed description of the decoherence processes coupling the muon-fluorine "system" with its "environment," and allowing us to track the system entropy as the quantum information degrades. These results show how to precisely quantify the spin relaxation of muons implanted into quantum entangled states in fluoride crystals.

Radiographer role extension in Oman - Current practice and future opportunities.

INTRODUCTION: Radiographers in Oman are believed to be engaged with varying levels of role extension however the nature and extent of this currently unknown. The aim of this study was to investigate role extension for radiographers in Oman, and to evaluate radiographers and the radiologists' opinions and attitudes toward role extension. METHODS: A cross sectional study of radiographers and radiologists at 13 major hospitals in Oman was used. A total of 189 radiographers and 77 radiologists were invited to complete a questionnaire seeking information on current and possible future role extension activities. RESULTS: The overall response rate was 80.4% for radiographers and 63.6% for radiologists. Approximately half (53.3%) of the radiographer respondents reported they carry out examinations traditionally performed by radiologists (i.e. role extension); this was primarily in gastrointestinal and barium enema studies. Fewer (21%) reported being involved in image interpretation, most commonly in accident and emergency examinations. Forty percent of radiographers reported involvement in intravenous injections, most commonly for CT and intravenous urography procedures. Both radiographers and radiologists supported the involvement of radiographers in a range of examination types however responses vary within and between hospitals. CONCLUSION: This study concluded that radiography role extension activities are widely implemented at hospitals in Oman and that radiographers have sufficient skills and education for participating in these activities. IMPLICATIONS FOR PRACTICE: The involvement of radiographers in role extension activities is believed to be cost and time effective, improve teamwork and has potential for significant service delivery benefits.

A new approach to comprehensively evaluate the morphological properties of the human femoral head: example of application to osteoarthritic joint.

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 µm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone.

Temporal trends and survivorship of total hip arthroplasty in very young patients: a study using the National Joint Registry data set.

AIMS: The aim of this study was to describe temporal trends and survivorship of total hip arthroplasty (THA) in very young patients, aged ≤ 20 years. PATIENTS AND METHODS: A descriptive observational study was undertaken using data from the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man between April 2003 and March 2017. All patients aged ≤ 20 years at the time of THA were included and the primary outcome was revision surgery. Descriptive statistics were used to summarize the data and Kaplan-Meier estimates calculated for the cumulative implant survival. RESULTS: A total of 769 THAs were performed in 703 patients. The median follow-up was 5.1 years (interquartile range (IQR) 2.6 to 7.8). Eight patients died and 35 THAs were revised. The use of metal-on-metal (MoM) bearings and resurfacing procedures declined after 2008. The most frequently recorded indications for revision were loosening (20%) and infection (20%), although the absolute risk of these events occurring was low (0.9%). Factors associated with lower implant survival were MoM and metal-on-polyethylene (MoP) bearings and resurfacing arthroplasty ( vs ceramic-on-polyethylene (CoP) and ceramic-on-ceramic (CoC) bearings, p = 0.002), and operations performed by surgeons who undertook few THAs in this age group as recorded in the NJR ( vs those with five or more recorded operations, p = 0.030). Kaplan-Meier estimates showed 96% (95% confidence interval (CI) 94% to 98%) survivorship of implants at five years. CONCLUSION: Within the NJR, the overall survival for very young patients undergoing THA exceeded 96% during the first five postoperative years. In the absence of studies that can better account for differences in the characteristics of the patients, surgeons should consider the association between early revision and the type of implant, the number of THAs performed in these patients, and the bearing surface when performing THA in very young patients. Cite this article: Bone Joint J 2018;100-B:1320-9.

Silage review: Animal and human health risks from silage.

Silage may contain several agents that are potentially hazardous to animal health, the safety of milk or other animal food products, or both. This paper reviews published literature about microbial hazards, plant toxins, and chemical hazards. Microbial hazards include Clostridium botulinum, Bacillus cereus, Listeria monocytogenes, Shiga toxin-producing Escherichia coli, Mycobacterium bovis, and various mold species. High concentrations of C. botulinum in silage have been associated with cattle botulism. A high initial concentration of C. botulinum spores in forage in combination with poor silage fermentation conditions can promote the growth of C. botulinum in silage. The elevated pH level that is generally associated with aerobic deterioration of silage is a major factor influencing concentrations of L. monocytogenes, Shiga toxin-producing E. coli, and molds in silage and may also encourage survival and growth of M. bovis, the bacterium that causes bovine tuberculosis. Soil is a major source of B. cereus spores in silage; growth of this bacterium in silage appears to be limited. Hazards from plant toxins include pyrrolizidine, tropane and tropolone alkaloids, phytoestrogens, prussic acid, and mimosine, compounds that exist naturally in certain plant species that may contaminate forages at harvesting. Another group of toxins belonging to this category are ergot alkaloids, which are produced by endophytic fungal species in forages such as tall fescue grass, sorghum, and ryegrass. Varying effects of ensiling on the degradation of these plant toxins have been reported. Chemical hazards include nitrate, nitrite, and toxic oxide gases of nitrogen produced from nitrate and high levels of butyric acid, biogenic amines, and ammonia. Chemical and microbiological hazards are associated with poorly fermented silages, which can be avoided by using proper silage-making practices and creating conditions that promote a rapid and sufficient reduction of the silage pH and prevent aerobic deterioration.

The risk of cardiac failure following metal-on-metal hip arthroplasty.

AIMS: The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM). PATIENTS AND METHODS: A linkage study between the National Joint Registry, Hospital Episodes Statistics and records of the Office for National Statistics on deaths was undertaken. Patients who underwent elective total hip arthroplasty between January 2003 and December 2014 with no past history of cardiac failure were included and stratified as having either a MoM (n = 53 529) or a non-MoM (n = 482 247) arthroplasty. The primary outcome measure was the time to an admission to hospital for cardiac failure or death. Analysis was carried out using data from all patients and from those matched by propensity score. RESULTS: The risk of cardiac failure was lower in the MoM cohort compared with the non-MoM cohort (adjusted hazard ratio (aHR) 0.901; 95% confidence interval (CI) 0.853 to 0.953). The risk of cardiac failure was similar following matching (aHR 0.909; 95% CI 0.838 to 0.987) and the findings were consistent in subgroup analysis. CONCLUSION: The risk of cardiac failure following total hip arthroplasty was not increased in those in whom MoM implants were used, compared with those in whom other types of prostheses were used, in the first seven years after surgery. Cite this article: Bone Joint J 2018;100-B:20-7.

Review: Use of human-edible animal feeds by ruminant livestock.

The drive to increase the output of animal product in some sectors of ruminant livestock production has led to greater use of feeds such as cereal grains and soyabean meal that are potentially human-edible. This trend has caused concern since, by so doing, ruminants compete not only with monogastric livestock but also with the human population for a limited global area of cultivatable land on which to produce grain crops. Reasons for using potentially human-edible feeds in ruminant diets include increased total daily energy intake, greater supply of essential amino acids and improved ruminal balance between fermentable energy and degradable protein. Soyabean meal, produced on land that has been in arable cultivation for many years can fulfil a useful role as a supplier of undegraded dietary protein in diets for high-yielding dairy cows. However, in the context of sustaining the production of high-quality foods from livestock to meet the demands of a growing human population, the use of potentially human-edible feed resources by livestock should be restricted to livestock with the highest daily nutrient requirements; that is, potentially human-edible feed inputs should be constrained to meeting requirements for energy and protein and to rectifying imbalances in nutrient supply from pastures and forage crops such as high concentrations of nitrogen (N). There is therefore a role for human-edible feeds in milk production because forage-only systems are associated with relatively low output per head and also low N use efficiency compared with systems with greater reliance on human-edible feeds. Profitability on farm is driven by control of input costs as well as product value and examples are given of low-cost bovine milk and meat production with little or no reliance on potentially human-edible feeds. In beef production, the forage-only systems currently under detailed real-time life-cycle analysis at the North Wyke Farm Platform, can sustain high levels of animal growth at low feed cost. The potential of all-forage diets should be demonstrated for a wide range of ruminant milk and meat production systems. The challenge for the future development of ruminant systems is to ensure that potentially human-edible feeds, or preferably human-inedible by-products if available locally, are used to complement pastures and forage crops strategically rather than replace them.

An analysis of 30-day mortality after weekend versus weekday elective joint arthroplasty in England and Wales: a cohort study using the National Joint Registry Dataset.

AIMS: To investigate whether elective joint arthroplasty performed at the weekend is associated with a different 30-day mortality versus that performed between Monday and Friday. PATIENTS AND METHODS: We examined the 30-day cumulative mortality rate (Kaplan-Meier) for all elective hip and knee arthroplasties performed in England and Wales between 1st April 2003 and 31st December 2014, comprising 118 096 episodes undertaken at the weekend and 1 233 882 episodes performed on a weekday. We used Cox proportional-hazards regression models to assess for time-dependent variation and adjusted for identified risk factors for mortality. RESULTS: The cumulative 30-day mortality for hip arthroplasty was 0.15% (95% confidence interval (CI) 0.12 to 0.19) for patients operated on at the weekend versus 0.20% (95% CI 0.19 to 0.21) for patients undergoing surgery during the normal working week. For knee arthroplasty, the cumulative 30-day mortality was 0.14% (95% CI 0.11 to 0.17) for weekend-operated patients versus 0.18% (95% CI 0.17 to 0.19) for weekday-operated patients. These differences were independent of any differences in patient age, gender, American Society of Anaesthesiologists grade, surgeon seniority, surgical and anaesthetic practices, and thromboprophylaxis choice in weekend versus weekday-operated patients. CONCLUSION: The 30-day mortality rate after elective joint arthroplasty is low. Surgery performed at the weekend is associated with lower post-operative mortality versus operations performed on a weekday. Cite this article: Bone Joint J 2017;99-B:1618-28.

Rates of hip and knee joint replacement amongst different ethnic groups in England: an analysis of National Joint Registry data.

OBJECTIVE: Despite a health care system that is free at the point of delivery, ethnic minorities may not always get care equitable to that of White patients in England. We examined whether ethnic differences exist in joint replacement rates and surgical practice in England. DESIGN: 373,613 hip and 428,936 knee National Joint Registry (NJR) primary replacement patients had coded ethnicity in Hospital Episode Statistics (HES). Age and gender adjusted observed/expected ratios of hip and knee replacements amongst ethnic groups were compared using indirect standardisation. Associations between ethnic group and type of procedure were explored and effects of demographic, clinical and hospital-related factors examined using multivariable logistic regression. RESULTS: Adjusted standardised observed/expected ratios were substantially lower in Blacks and Asians than Whites for hip replacement (Blacks 0.33 [95% CI, 0.31-0.35], Asians 0.20 [CI, 0.19-0.21]) and knee replacement (Blacks 0.64 [CI, 0.61-0.67], Asians 0.86 % [CI, 0.84-0.88]). Blacks were more likely to receive uncemented hip replacements (Blacks 52%, Whites 37%, Asians 44%; P < 0.001). Black men and women aged <70 years were less likely to receive unicondylar or patellofemoral knee replacements than Whites (men 10% vs 15%, P = 0.001; women 6% vs 14%, P < 0.001). After adjustment for demographic, clinical and hospital-related factors, Blacks were more likely to receive uncemented hip replacement (OR 1.43 [CI, 1.11-1.84]). CONCLUSIONS: In England, hip and knee replacement rates and prosthesis type given differ amongst ethnic groups. Whether these reflect differences in clinical need or differential access to treatment requires urgent investigation.

Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions.

Bone is established as the preferred site of breast cancer metastasis. However, the precise mechanisms responsible for this preference remain unidentified. In order to improve outcome for patients with advanced breast cancer and skeletal involvement, we need to better understand how this process is initiated and regulated. As bone metastasis cannot be easily studied in patients, researchers have to date mainly relied on in vivo xenograft models. A major limitation of these is that they do not contain a human bone microenvironment, increasingly considered to be an important component of metastases. In order to address this shortcoming, we have developed a novel humanised bone model, where 1 × 10(5) luciferase-expressing MDA-MB-231 or T47D human breast tumour cells are seeded on viable human subchaodral bone discs in vitro. These discs contain functional osteoclasts 2-weeks after in vitro culture and positive staining for calcine 1-week after culture demonstrating active bone resorption/formation. In vitro inoculation of MDA-MB-231 or T47D cells colonised human bone cores and remained viable for <4 weeks, however, use of matrigel to enhance adhesion or a moving platform to increase diffusion of nutrients provided no additional advantage. Following colonisation by the tumour cells, bone discs pre-seeded with MDA-MB-231 cells were implanted subcutaneously into NOD SCID mice, and tumour growth monitored using in vivo imaging for up to 6 weeks. Tumour growth progressed in human bone discs in 80 % of the animals mimicking the later stages of human bone metastasis. Immunohistochemical and PCR analysis revealed that growing MDA-MB-231 cells in human bone resulted in these cells acquiring a molecular phenotype previously associated with breast cancer bone metastases. MDA-MB-231 cells grown in human bone discs showed increased expression of IL-1B, HRAS and MMP9 and decreased expression of S100A4, whereas, DKK2 and FN1 were unaltered compared with the same cells grown in mammary fat pads of mice not implanted with human bone discs.

Systemic toxicity related to metal hip prostheses.

INTRODUCTION: One in eight of all total hip replacements requires revision within 10 years, 60% because of wear-related complications. The bearing surfaces may be made of cobalt/chromium, stainless steel, ceramic, or polyethylene. Friction between bearing surfaces and corrosion of non-moving parts can result in increased local and systemic metal concentrations. OBJECTIVES: To identify and systematically review published reports of systemic toxicity attributed to metal released from hip implants and to propose criteria for the assessment of these patients. METHODS: Medline (from 1950) and Embase (from 1980) were searched to 28 February 2014 using the search terms (text/abstract) chrom* or cobalt* and [toxic* or intox* or poison* or adverse effect or complication] and [prosthes* or 'joint replacement' or hip or arthroplast*] and PubMed (all available years) was searched using the search term (("Chromium/adverse effects"[Mesh] OR "Chromium/poisoning"[Mesh] OR "Chromium/toxicity"[Mesh]) OR ("Cobalt/adverse effects"[Mesh] OR "Cobalt/poisoning"[Mesh] OR "Cobalt/toxicity"[Mesh])) AND ("Arthroplasty, Replacement, Hip"[Mesh] OR "Hip Prosthesis"[Mesh]). These searches identified 281 unique references, of which 23 contained original case data. Three further reports were identified from the bibliographies of these papers. As some cases were reported repeatedly the 26 papers described only 18 individual cases. Systemic toxicity. Ten of these eighteen patients had undergone revision from a ceramic-containing bearing to one containing a metal component. The other eight had metal-on-metal prostheses. Systemic toxicity was first manifest months and often several years after placement of the metal-containing joint. The reported systemic features fell into three main categories: neuro-ocular toxicity (14 patients), cardiotoxicity (11 patients) and thyroid toxicity (9 patients). Neurotoxicity was manifest as peripheral neuropathy (8 cases), sensorineural hearing loss (7) and cognitive decline (5); ocular toxicity presented as visual impairment (6). All these neurological features, except cognitive decline, have been associated with cobalt poisoning previously. Type of prosthesis and blood metal concentrations. Where blood or serum metal concentrations were reported (n = 17 for cobalt and n = 14 for chromium), the median cobalt concentration was 398 (range, 13.6-6521) µg/L and the median chromium concentration was 48 µg/L (in whole blood) (range, 4.1-221 µg/L including serum and blood values). Those patients reported to have systemic features who had received a metal-on-metal prosthesis (n = 8) had a median peak blood cobalt concentration of 34.5 (range, 13.6-398.6) µg/L; those with a metal-containing revision of a failed ceramic prosthesis (n = 10) had a median blood cobalt concentration of 506 (range, 353-6521) µg/L. Management. The most common treatment was removal of the metal-containing prosthesis, undertaken in all but 2 patients. This was usually associated with a fall in circulating cobalt concentration and improvement in some or all features. Clinical and toxicological assessment of systemic features. We propose the following criteria for assessing the likelihood that clinical features are related to cobalt toxicity: clinical effects consistent with the known neurological, cardiac, or thyroidal effects of cobalt, and for which any other explanation is less likely; increased blood cobalt concentrations (substantially higher than those in patients with well-functioning prostheses) several months after hip replacement; a fall in the blood cobalt concentration, usually accompanied by signs of improvement in features. When judged by these criteria, the systemic features in 10 of the reported cases are likely to be related to cobalt exposure from a metal-containing hip prosthesis. CONCLUSIONS: Rarely, patients exposed to high circulating concentrations of cobalt from failed hip replacements develop neurological damage, hypothyroidism and/or cardiomyopathy, which may not resolve completely even after removal of the prosthesis. The greatest risk of systemic cobalt toxicity seems to result from accelerated wear of a cobalt-containing revision of a failed ceramic prosthesis, rather than from primary failure of a metal-on-metal prosthesis.

Brain structure and function in patients after metal-on-metal hip resurfacing.

BACKGROUND AND PURPOSE: Hip prostheses that use a metal-on-metal articulation expose the brain to elevated metal concentrations that, in acute excess due to prosthesis malfunction, is associated with neurologic damage, including visual and hearing loss and motor deficits. Here, we examined whether chronic exposure to lower elevated metal levels, typical of well-functioning prostheses, also affects brain structure and function. MATERIALS AND METHODS: We compared brain volumes, metal deposition, and gray matter attenuation by MR imaging and clinical neurologic function in patients 8 years after receiving a metal-on-metal hip resurfacing versus a matched group of patients with the same duration exposure to a conventional hip prosthesis. RESULTS: Twenty-nine patients (25 men; mean, age 59±7 years) after metal-on-metal hip resurfacing and 29 patients (25 men; 59±8 years) after total hip arthroplasty were compared. Whole blood cobalt and chromium concentrations were 5-10 times higher in the metal-on-metal hip resurfacing group (P<.0001). Occipital cortex gray matter attenuation tended to be lower (P<.005 uncorrected, P>.05 corrected), and the optic chiasm area tended to be lower (mean difference, -2.7 mm2; P=.076) in the metal-on-metal hip resurfacing group. Subgroup analyses in 34 patients (17 per group), after exclusion of primary ocular pathology, showed the same trend in gray matter attenuation in the occipital cortex and basal ganglia and a smaller optic chiasm in the metal-on-metal hip resurfacing group (mean difference, -3.9 mm2; P=.048). No other structural or functional differences were found between the groups. CONCLUSIONS: Chronic exposure to metal-on-metal hip resurfacing is associated with subtle structural change in the visual pathways and the basal ganglia in asymptomatic patients.

Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1ß induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes.

OBJECTIVE: Interleukin-1ß (IL-1ß) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) may inhibit cartilage degradation. METHODS: Effects of WIN-55 were studied on IL-1ß stimulated production of MMP-3 and -13 and their inhibitors TIMP-1 and -2 in human chondrocytes. Chondrocytes were obtained from articular cartilage of patients undergoing total knee replacement. Chondrocytes were grown in monolayer and 3D alginate bead cultures. Real-time polymerase chain reaction (PCR) was used to determine the gene expression of MMP-3, -13, TIMP-1 and -2 and Enzyme Linked Immunosorbent Assay (ELISA) to measure the amount of MMP-3 and MMP-13 protein released into media. Immunocytochemistry was used to investigate the expression of cannabinoid receptors in chondrocyte cultures. RESULTS: Treatment with WIN-55 alone or in combination with IL-1ß, decreased or abolished MMP-3, -13, TIMP-1 and -2 gene expression in human chondrocyte monolayer and alginate bead cultures in both a concentration and time dependent manner. WIN-55 treatment alone, and in combination with IL-1ß, reduced MMP-3 and -13 protein production by chondrocytes cultured in alginate beads. Immunocytochemistry demonstrated the expression of cannabinoid receptors in chondrocyte cultures. CONCLUSION: Cannabinoid WIN-55 can reduce both basal and IL-1ß stimulated gene and protein expression of MMP-3 and -13. However WIN-55 also decreased basal levels of TIMP-1 and -2 mRNA. These actions of WIN-55 suggest a mechanism by which cannabinoids may act to prevent cartilage breakdown in arthritis.

Use of kernel-based Bayesian models to predict late osteolysis after hip replacement.

We studied the relationship between osteolysis and polyethylene wear, age at surgery, body mass index and height in 463 subjects (180 osteolysis and 283 controls) after cemented Charnley total hip arthroplasty (THA), in order to develop a kernel-based Bayesian model to quantitate risk of osteolysis. Such tools may be integrated into decision-making algorithms to help personalize clinical decision-making. A predictive model was constructed, and the estimated posterior probability of the implant failure calculated. Annual wear provided the greatest discriminatory information. Age at surgery provided additional predictive information and was added to the model. Body mass index and height did not contain valuable discriminatory information over the range in which observations were densely sampled. The robustness and misclassification rate of the predictive model was evaluated by a five-times cross-validation method. This yielded a 70% correct predictive classification of subjects into osteolysis versus non-osteolysis groups at a mean of 11 years after THA. Finally, the data were divided into male and female subsets to further explore the relationship between wear rate, age at surgery and incidence of osteolysis. The correct classification rate using age and wear rate in the model was approximately 66% for males and 74% for females.

Development of a fully automatic shape model matching (FASMM) system to derive statistical shape models from radiographs: application to the accurate capture and global representation of proximal femur shape.

OBJECTIVE: To evaluate the accuracy and sensitivity of a fully automatic shape model matching (FASMM) system to derive statistical shape models (SSMs) of the proximal femur from non-standardised anteroposterior (AP) pelvic radiographs. DESIGN: AP pelvic radiographs obtained with informed consent and appropriate ethical approval were available for 1105 subjects with unilateral hip osteoarthritis (OA) who had been recruited previously for The arcOGEN Study. The FASMM system was applied to capture the shape of the unaffected (i.e., without signs of radiographic OA) proximal femur from these radiographs. The accuracy and sensitivity of the FASMM system in calculating geometric measurements of the proximal femur and in shape representation were evaluated relative to validated manual methods. RESULTS: De novo application of the FASMM system had a mean point-to-curve error of less than 0.9 mm in 99% of images (n = 266). Geometric measurements generated by the FASMM system were as accurate as those obtained manually. The analysis of the SSMs generated by the FASMM system for male and female subject groups identified more significant differences (in five of 17 SSM modes after Bonferroni adjustment) in their global proximal femur shape than those obtained from the analysis of conventional geometric measurements. Multivariate gender-classification accuracy was higher when using SSM mode values (76.3%) than when using conventional hip geometric measurements (71.8%). CONCLUSIONS: The FASMM system rapidly and accurately generates a global SSM of the proximal femur from radiographs of varying quality and resolution. This system will facilitate complex morphometric analysis of global shape variation across large datasets. The FASMM system could be adapted to generate SSMs from the radiographs of other skeletal structures such as the hand, knee or pelvis.

Fully automatic segmentation of the proximal femur using random forest regression voting.

Extraction of bone contours from radiographs plays an important role in disease diagnosis, preoperative planning, and treatment analysis. We present a fully automatic method to accurately segment the proximal femur in anteroposterior pelvic radiographs. A number of candidate positions are produced by a global search with a detector. Each is then refined using a statistical shape model together with local detectors for each model point. Both global and local models use Random Forest regression to vote for the optimal positions, leading to robust and accurate results. The performance of the system is evaluated using a set of 839 images of mixed quality. We show that the local search significantly outperforms a range of alternative matching techniques, and that the fully automated system is able to achieve a mean point-to-curve error of less than 0.9 mm for 99% of all 839 images. To the best of our knowledge, this is the most accurate automatic method for segmenting the proximal femur in radiographs yet reported.

A preliminary study of complementary and alternative medicine (CAM) practitioners in Singapore.

OBJECTIVES: To investigate the profile and health attitudes of complementary and alternative medicine (CAM) practitioners in Singapore. DESIGN AND SETTING: A descriptive survey with convenience and snowball sampling were used. An anonymous self-administered survey was sent to 130 practitioners found in publicly accessible online practitioner registers, groups, and directories practicing CAM modalities from April 2010 to October 2010. MAIN OUTCOME MEASURES: Participants' demographics, business structure, and attitudes towards health, CAM and orthodox medicine (OM). RESULTS: Response rate was 32%. The data suggest that the typical CAM practitioner in Singapore is a middle-aged female who specialises in more than one CAM modality. Almost half (45%) of the participants possessed a degree and massage is the most commonly practiced modality. Participants practiced an average of 2-3 therapies and group-practice size ranged from 2 to 15 practitioners. Most participants (69%) experienced a radical change in job type to become a CAM practitioner and their previous employment suggests a slightly middle-class profile. The cost and duration of initial consultation and treatment ranged from SG$20 to SG$345 and 30-120min, respectively. The most common source of CAM information was seminars/lectures/workshops (76%). Communication and referral between CAM and orthodox medicine practitioners are high (>70%). Participants perceived CAM to be more suitable for disease prevention than treatment of serious medical conditions. CONCLUSIONS: This study provides important base-line data that will help future researchers explore further Singaporean CAM practitioners' business aspirations, and attitudes towards regulation and integration with OM.