In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (± 2) after knee and 35 days (± 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)).

Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding.

This is the first study to use the English Indices of Multiple Deprivation 2007, the Government’s official measure of multiple deprivation, to analyse the effect of socioeconomic status on the incidence of fractures of the hip and their outcome and mortality. Our sample consisted of all patients admitted to hospital with a fracture of the hip (n = 7511) in Nottingham between 1999 and 2009.

The incidence was 1.3 times higher (p = 0.038) in the most deprived populations than in the least deprived; the most deprived suffered a fracture, on average, 1.1 years earlier (82.0 years versus 83.1 years, p < 0.001). The mortality rate proved to be significantly higher in the most deprived population (log-rank test, p = 0.033), who also had a higher number of comorbidities (p = 0.001).

This study has shown an increase in the incidence of fracture of the hip in the most deprived population, but no association between socioeconomic status and mortality at 30 days. Preventative programmes aimed at reducing the risk of hip fracture should be targeted towards the more deprived if they are to make a substantial impact.

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.

We describe the results of arthrodesis for the treatment of recurrent acute neuropathic bone disease in 24 feet and of chronic disease with deformity in 91 feet, undertaken between January 1984 and December 2003. All were due to leprosy.

Correction of the deformity was achieved in 80 of 106 feet (76%) and fusion in 97 of 110 feet (88%). In the 24 feet in which recurrent neuropathic bone disease was the reason for surgery, 17 (71%) obtained stability while in seven (29%) symptoms recurred postoperatively. Complications were experienced following 58 of the 110 operations (53%). In patients presenting primarily with deformity with a minimum follow-up of two years (79 feet), there was a reduced frequency of ulceration in 40 (51%). Normal footwear could be worn by 32 patients (40%) after surgery, while 40 (51%) required a moulded insole. Arthrodesis of the ankle in the neuropathic foot due to leprosy has a good overall rate of success although the rate of complications is high.

A silver-containing hydroxyapatite (Ag-HA) coating has been developed using thermal spraying technology. We evaluated the osteoconductivity of this coating on titanium (Ti) implants in rat tibiae in relation to bacterial infection in joint replacement.

At 12 weeks, the mean affinity indices of bone formation of a Ti, an HA, a 3%Ag-HA and a 50%Ag-HA coating were 97.3%, 84.9%, 81.0% and 40.5%, respectively. The mean affinity indices of bone contact of these four coatings were 18.8%, 83.7%, 77.2% and 40.5%, respectively. The indices of bone formation and bone contact around the implant of the 3%Ag-HA coating were similar to those of the HA coating, and no significant differences were found between them (bone formation, p = 0.99; bone contact, p = 0.957). However, inhibition of bone formation was observed with the 50%Ag-HA coating.

These results indicate that the 3%Ag-HA coating has low toxicity and good osteoconductivity, and that the effect of silver toxicity on osteoconductivity depends on the dose.

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.

The purpose of this study was to assess the long-term results (more than ten years) of two types of cemented ulnar component with type-5 Kudo total elbow arthroplasty in a consecutive series of 56 patients (60 elbows) with rheumatoid arthritis, and to compare the results in elbows above and below a Larsen grade IV.

There was no radiolucency around the humeral component. Patients in whom a metal-backed ulnar component and a porous-coated stem were used had better clinical results and significantly less progression of radiolucent line formation around the ulnar component. They also had a significantly better long-term survival than patients with an all-polyethylene ulnar component. The clinical results of arthroplasty using all-polyethylene ulnar components were inferior, regardless of the degree of joint destruction.

We conclude that the type-5 Kudo total elbow arthroplasty with cementless fixation of the porous-coated humeral component and cemented fixation of a metal-backed ulnar component is acceptable and well-tolerated by rheumatoid patients.

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.

We reviewed 183 patients who had undergone reconstruction of the anterior cruciate ligament. The incidence of meniscal tears and degenerative change was assessed and related to the timing from injury to surgery. Degenerative change was scored using the French Society of Arthroscopy system. The patients were divided into an early (surgery within 12 months of injury) and a late group (surgery more than 12 months from injury). The late group was also subdivided into four groups of 12-month periods ranging from one year to more than four years after injury.

There was a significantly higher incidence of meniscal tears in patients undergoing reconstruction after 12 months compared with those in the early group (71.2% vs 41.7%; p < 0.001). This was due to a large increase in medial meniscal tears in the late group. An increased incidence of degenerative change was also found in the late group (31.3% vs 10.7%; p < 0.001). Analysis of the subgroups showed that the incidence of meniscal tears and degenerative change did not differ significantly when surgery was performed after 12 months from injury. We conclude that reconstruction of the anterior cruciate ligament should be carried out within 12 months of injury to minimise the risk of meniscal tears and degenerative change.

We studied the effects of hyperbaric oxygen (HBO) and zoledronic acid (ZA) on posterior lumbar fusion using a validated animal model. A total of 40 New Zealand white rabbits underwent posterior lumbar fusion at L5–6 with autogenous iliac bone grafting. They were divided randomly into four groups as follows: group 1, control; group 2, HBO (2.4 atm for two hours daily); group 3, local ZA (20 μg of ZA mixed with bone graft); and group 4, combined HBO and local ZA. All the animals were killed six weeks after surgery and the fusion segments were subjected to radiological analysis, manual palpation, biomechanical testing and histological examination.

Five rabbits died within two weeks of operation. Thus, 35 rabbits (eight in group 1 and nine in groups 2, 3 and 4) completed the study. The rates of fusion in groups 3 and 4 (p = 0.015) were higher than in group 1 (p < 0.001) in terms of radiological analysis and in group 4 was higher than in group 1 with regard to manual palpation (p = 0.015). We found a statistically significant difference in the biomechanical analysis between groups 1 and 4 (p = 0.024). Histological examination also showed a statistically significant difference between groups 1 and 4 (p = 0.036).

Our results suggest that local ZA combined with HBO may improve the success rate in posterior lumbar spinal fusion.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

This paper outlines the history of advances made in the treatment of open fractures that have occurred during wartime.

We retrospectively evaluated 18 patients with a mean age of 37.3 years (14 to 72) who had undergone pelvic reconstruction stabilised with a non-vascularised fibular graft after resection of a primary bone tumour. The mean follow-up was 10.14 years (2.4 to 15.7). The mean Musculoskeletal Tumor Society Score was 76.5% (50% to 100%). Primary union was achieved in the majority of reconstructions within a mean of 22.9 weeks (7 to 60.6). The three patients with delayed or nonunion all received additional therapy (chemotherapy/radiation) (p = 0.0162). The complication rate was comparable to that of other techniques described in the literature.

Non-vascularised fibular transfer to the pelvis is a simpler, cheaper and quicker procedure than other currently described techniques. It is a biological reconstruction with good results and a relatively low donor site complication rate. However, adjuvant therapy can negatively affect the outcome of such grafts.

Antibiotic prophylaxis is routinely administered during joint replacement surgery and may predispose patients to Clostridium difficile-associated disease (CDAD). The primary aim of this study was to determine the incidence of this following joint replacement, using a cefuroxime-based regimen. Patients developing CDAD were compared with a control group of patients without CDAD. The incidence of the former was 1.7 per 1000 primary joint replacements. Those patients prescribed additional antibiotics had a higher incidence of CDAD (p = 0.047), but there was no difference between the two groups in relation to the use of gastroprotective agents (p = 0.703). A trial of a new prophylaxis regimen would require 43 198 patients in each arm to show a reduction of one case per 1000 procedures. Cefuroxime-based antibiotic prophylaxis is safe in patients undergoing primary elective joint replacement.

Infection remains a significant and common complication after joint replacement and there is debate about which contributing factors are important. Few studies have investigated the effect of the operating time on infection.

We collected data prospectively from 5277 hip and knee replacements which included the type of procedure, the operating time, the use of drains, the operating theatre, surgeon, age and gender. In a subgroup of 3449 knee replacements further analysis was carried out using the tourniquet time in place of the operating time. These variables were assessed by the use of generalised linear modelling against superficial, deep or joint-space post-operative infection as defined by the Australian Surgical-Site Infection criteria.

The overall infection rate was 0.98%. In the replacement data set both male gender (z = 3.097, p = 0.00195) and prolonged operating time (z = 4.325, p < 0.001) were predictive of infection. In the knee subgroup male gender (z = 2.250, p = 0.02447), a longer tourniquet time (z = 2.867, p = 0.00414) and total knee replacement (versus unicompartmental knee replacement) (z = −2.052, p = 0.0420) were predictive of infection.

These findings support the view that a prolonged operating time and male gender are associated with an increased incidence of infection. Steps to minimise intra-operative delay should be instigated, and care should be exercised when introducing measures which prolong the duration of joint replacement.

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13.

In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six.

We concluded that SAA is better than CRP as a post-operative inflammatory marker.

The aim of this study was to analyse the functional outcome after a displaced intracapsular fracture of the femoral neck in active patients aged over 70 years without osteoarthritis or rheumatoid arthritis of the hip, randomised to receive either a hemiarthroplasty or a total hip replacement (THR). We studied 252 patients of whom 47 (19%) were men, with a mean age of 81.1 years (70.2 to 95.6). They were randomly allocated to be treated with either a cemented hemiarthroplasty (137 patients) or cemented THR (115 patients). At one- and five-year follow-up no differences were observed in the modified Harris hip score, revision rate of the prosthesis, local and general complications, or mortality. The intra-operative blood loss was lower in the hemiarthroplasty group (7% > 500 ml) than in the THR group (26% > 500 ml) and the duration of surgery was longer in the THR group (28% > 1.5 hours versus 12% > 1.5 hours). There were no dislocations of any bipolar hemiarthroplasty and eight dislocations of a THR during follow-up.

Because of a higher intra-operative blood loss (p < 0.001), an increased duration of the operation (p < 0.001) and a higher number of early and late dislocations (p = 0.002), we do not recommend THR as the treatment of choice in patients aged ≥ 70 years with a fracture of the femoral neck in the absence of advanced radiological osteoarthritis or rheumatoid arthritis of the hip.

Following the publication in 2007 of the guidelines from the National Institute for Health and Clinical Excellence (NICE) for prophylaxis against venous thromboembolism (VTE) for patients undergoing surgery, concerns were raised by British orthopaedic surgeons as to the appropriateness of the recommendations for their clinical practice. In order to address these concerns NICE and the British Orthopaedic Association agreed to engage a representative panel of orthopaedic surgeons in the process of developing expanded VTE guidelines applicable to all patients admitted to hospital. The functions of this panel were to review the evidence and to consider the applicability and implications in orthopaedic practice in order to advise the main Guideline Development Group in framing recommendations.

The panel considered both direct and indirect evidence of the safety and efficacy, the cost-effectiveness of prophylaxis and its implication in clinical practice for orthopaedic patients. We describe the process of selection of the orthopaedic panel, the evidence considered and the contribution of the panel to the latest guidelines from NICE on the prophylaxis against VTE, published in January 2010.