Showing papers by "Nuffield Orthopaedic Centre published in 2014"

Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis--a clinical study using myocardial T1-mapping and extracellular volume quantification.

Abstract: Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc. 19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification. Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p 990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices. Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc.

Meta-ethnography 25 years on: challenges and insights for synthesising a large number of qualitative studies.

Abstract: Studies that systematically search for and synthesise qualitative research are becoming more evident in health care, and they can make an important contribution to patient care. Our team was funded to complete a meta-ethnography of patients’ experience of chronic musculoskeletal pain. It has been 25 years since Noblit and Hare published their core text on meta-ethnography, and the current health research environment brings additional challenges to researchers aiming to synthesise qualitative research. Noblit and Hare propose seven stages of meta-ethnography which take the researcher from formulating a research idea to expressing the findings. These stages are not discrete but form part of an iterative research process. We aimed to build on the methods of Noblit and Hare and explore the challenges of including a large number of qualitative studies into a qualitative systematic review. These challenges hinge upon epistemological and practical issues to be considered alongside expectations about what determines high quality research. This paper describes our method and explores these challenges. Central to our method was the process of collaborative interpretation of concepts and the decision to exclude original material where we could not decipher a concept. We use excerpts from our research team’s reflexive statements to illustrate the development of our methods.

The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of chronic osteomyelitis: a series of 195 cases.

Abstract: We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny-Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation. We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Percutaneous fixation with Kirschner wires versus volar locking plate fixation in adults with dorsally displaced fracture of distal radius: randomised controlled trial.

Abstract: Objectives To compare the clinical effectiveness of Kirschner wire fixation with locking plate fixation for patients with a dorsally displaced fracture of the distal radius. Design A multicentre two arm parallel group assessor blind randomised controlled trial with 1:1 treatment allocation. Setting 18 trauma centres in the United Kingdom. Participants 461 adults with a dorsally displaced fracture of the distal radius within 3 cm of the radiocarpal joint that required surgical fixation. Patients were excluded if the surgeon thought that the surface of the wrist joint was so badly displaced it required open reduction. Interventions Kirschner wire fixation: wires are passed through the skin over the dorsal aspect of the distal radius and into the bone to hold the fracture in the correct anatomical position. Locking plate fixation: a locking plate is applied through an incision over the volar (palm) aspect of the wrist and secured to the bone with fixed angle locking screws. Main outcome measures Primary outcome measure: validated patient rated wrist evaluation (PRWE). This rates wrist function in two (equally weighted) sections concerning the patient’s experience of pain and disability to give a score out of 100. Secondary outcomes: disabilities of arm, shoulder, and hand (DASH) score, the EuroQol (EQ-5D), and complications related to the surgery. Results The baseline characteristics of the two groups were well balanced, and over 90% of patients completed follow-up. The wrist function of both groups of patients improved by 12 months. There was no clinically relevant difference in the patient rated wrist score at three, six, or 12 months (difference in favour of the plate group was −1.3, 95% confidence interval −4.5 to 1.8; P=0.40). Nor was there a clinically relevant difference in health related quality of life or the number of complications in each group. Conclusions Contrary to the existing literature, and against the rapidly increasing use of locking plate fixation, this trial found no difference in functional outcome in patients with dorsally displaced fractures of the distal radius treated with Kirschner wires or volar locking plates. Kirschner wire fixation, however, is cheaper and quicker to perform. Trial registration Current Controlled Trials ISCRTN 31379280. UKCRN 8956.

National Osteoporosis Society Vitamin D Guideline Summary

Abstract: The National Osteoporosis Society (NOS) published its document, Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a practical clinical guideline on the management of vitamin D deficiency in adult patients with, or at risk of developing, bone disease. There has been no clear consensus in the UK on vitamin D deficiency its assessment and treatment, and clinical practice is inconsistent. This guideline is aimed at clinicians, including doctors, nurses and dieticians. It recommends the measurement of serum 25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical scenarios: bone diseases that may be improved with vitamin D treatment; bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate; musculoskeletal symptoms that could be attributed to vitamin D deficiency. The guideline also states that routine vitamin D testing is unnecessary where vitamin D supplementation with an oral antiresorptive treatment is already planned and sets the following serum 25OHD thresholds: 50 nmol/l is sufficient for almost the whole population. For treatment, oral vitamin D3 is recommended with fixed loading doses of oral vitamin D3 followed by regular maintenance therapy when rapid correction of vitamin D deficiency is required, although loading doses are not necessary where correction of deficiency is less urgent or when co-prescribing with an oral antiresorptive agent. For monitoring, serum calcium (adjusted for albumin) should be checked 1 month after completing a loading regimen, or after starting vitamin D supplementation, in case primary hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected. The guideline focuses on bone health as, although there are numerous putative effects of vitamin D on immunity modulation, cancer prevention and the risks of cardiovascular disease and multiple sclerosis, there remains considerable debate about the evaluation of extraskeletal factors and optimal vitamin D status in these circumstances.

Use of an automated blood culture system (BD BACTEC™) for diagnosis of prosthetic joint infections: easy and fast.

Abstract: For the diagnosis of prosthetic joint infection (PJI) automated BACTEC™ blood culture bottle methods have comparable sensitivity, specificity and a shorter time to positivity than traditional cooked meat enrichment broth methods. We evaluate the culture incubation period required to maximise sensitivity and specificity of microbiological diagnosis, and the ability of BACTEC™ to detect slow growing Propionibacteria spp. Multiple periprosthetic tissue samples taken by a standardised method from 332 patients undergoing prosthetic joint revision arthroplasty were cultured for 14 days, using a BD BACTEC™ instrumented blood culture system, in a prospective study from 1st January to 31st August 2012. The “gold standard” definition for PJI was the presence of at least one histological criterion, the presence of a sinus tract or purulence around the device. Cases where > =2 samples yielded indistinguishable isolates were considered culture-positive. 1000 BACTEC™ bottle cultures which were negative after 14 days incubation were sub-cultured for Propionibacteria spp. 79 patients fulfilled the definition for PJI, and 66 of these were culture-positive. All but 1 of these 66 culture-positive cases of PJI were detected within 3 days of incubation. Only one additional (clinically-insignificant) Propionibacterium spp. was identified on terminal subculture of 1000 bottles. Prolonged microbiological culture for 2 weeks is unnecessary when using BACTEC™ culture methods. The majority of clinically significant organisms grow within 3 days, and Propionibacteria spp. are identified without the need for terminal subculture. These findings should facilitate earlier decisions on final antimicrobial prescribing.

The clinical presentation of prosthetic joint infection

Abstract: Prosthetic joint infection (PJI) complicates ∼1% of arthroplasties but accounts for considerable morbidity. Both the timing and features of PJI can vary widely. Patients may present with early (≤3 months post-operatively), delayed (3-24 months) or late disease (>24 months). They may be acutely unwell with systemic signs of sepsis or describe only a chronically painful joint with or without sinus formation. Diagnostic criteria as proposed by the Infectious Diseases Society of America and the Musculoskeletal Infection Society highlight the importance of joint sampling to obtain histological and robust microbiological evidence. Staphylococcus aureus and coagulase-negative staphylococci account for >50% of infections. Early infections are likely to have been acquired intra- or peri-operatively, whereas late infection is usually haematogenous in origin. Acute joint inflammation suggests the presence of intra-articular free-living bacteria, whereas chronic infections are associated with the formation of biofilm at the bone-cement or bone-prosthesis interface. The most significant risk factors predisposing to PJI are previous operation on the index joint, previous arthroplasty at a different site, American Society of Anesthesiologists' grade 2, 3 or 4, body mass index >25, malignancy and procedure duration 4 h.

Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?

Abstract: Background Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon. Study design Controlled laboratory study. Methods Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry. Results There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1α (HIF-1α) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N -methyl-d-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016). Conclusions The increases in cell proliferation, vascularity and HIF-1α after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment.

ISSLS Prize winner: Long-term follow-up suggests spinal fusion is associated with increased adjacent segment disc degeneration but without influence on clinical outcome: results of a combined follow-up from 4 randomized controlled trials

Abstract: Study design Cross-sectional analysis of long-term follow-up (LTFU) data from 4 randomized controlled trials of operative versus nonoperative treatment for chronic low back pain. Objective To examine the influence of spinal fusion on adjacent segment disc space height as an indicator of disc degeneration at LTFU. Summary of background data There is ongoing debate as to whether adjacent segment disc degeneration results from the increased mechanical stress of fusion. Methods Plain standing lateral radiographs were obtained at LTFU (mean, 13 ± 4 yr postrandomization) in 229 of 464 (49%) patients randomized to surgery and 140 of 303 (46%), to nonoperative care. Disc space height and posteroanterior displacement were measured for each lumbar segment using a validated computer-assisted distortion compensated roentgen analysis technique. Values were reported in units of standard deviations above or below age and sex-adjusted normal values. Patient-rated outcomes included the Oswestry Disability Index and pain scales. Results Radiographs were usable in 355 of 369 (96%) patients (259 fusion and 96 nonoperative treatment). Both treatment groups showed significantly lower values for disc space height of the adjacent segment than norm values. There was a significant difference between treatment groups for the disc space height of the cranial adjacent segment (in both as-treated and intention-to-treat analyses). The mean treatment effect of fusion on adjacent segment disc space height was -0.44 SDs (95% CI, -0.77 to -0.11; P = 0.01; as-treated analysis); there was no group difference for posteroanterior displacement (0.18 SDs, 95% confidence interval, -0.28 to 0.64, P = 0.45). Adjacent level disc space height and posteroanterior displacement were not correlated with Oswestry Disability Index or pain scores at LTFU (r = 0.010-0.05; P > 0.33). Conclusion Fusion was associated with lower disc space height at the adjacent segment after an average of 13 years of FU. The reduced disc space height had no influence on patient self-rated outcomes (pain or disability). Level of evidence 2.

Why are there different versions of the Oswestry Disability Index

Abstract: This article updates readers on the current state of the Oswestry Disability Index (ODI) and the impact of unvalidated versions. The ODI is now licensed to the Mapi Research Trust in order to preserve a standard version in English and in validated translations. A proposed threshold of “normality” is potentially helpful as an outcome for both audit and research. There is an application of the sex section as a quality measure in Germany. The ODI is an important international shared resource for clinicians and investigators and should not be abused. Its current status will not be enhanced by further modification. It is now registered with the International Consortium for Health Outcomes Measurement as a standard outcome measure.

The mid-term outcomes of the Oxford Domed Lateral unicompartmental knee replacement

Abstract: Mobile-bearing unicompartmental knee replacements (UKRs) with a flat tibial plateau have not performed well in the lateral compartment, owing to a high dislocation rate. This led to the development of the Domed Lateral Oxford UKR (Domed OUKR) with a biconcave bearing. The aim of this study was to assess the survival and clinical outcomes of the Domed OUKR in a large patient cohort in the medium term. We prospectively evaluated 265 consecutive knees with isolated disease of the lateral compartment and a mean age at surgery of 64 years (32 to 90). At a mean follow-up of four years (sd 2.2, (0.5 to 8.3)) the mean Oxford knee score was 40 out of 48 (sd 7.4). A total of 12 knees (4.5%) had re-operations, of which four (1.5%) were for dislocation. All dislocations occurred in the first two years. Two (0.8%) were secondary to significant trauma that resulted in ruptured ligaments, and two (0.8%) were spontaneous. In four patients (1.5%) the UKR was converted to a primary TKR. Survival at eight years, with failure defined as any revision, was 92.1% (95% confidence interval 81.3 to 100). The Domed Lateral OUKR gives good clinical outcomes, low re-operation and revision rates and a low dislocation rate in patients with isolated lateral compartmental disease, in the hands of the designer surgeons. Cite this article: Bone Joint J 2014;96-B:59–64.

Bisphosphonates and bone quality.

Abstract: Bisphosphonates (BPs) are bone-avid compounds used as first-line medications for the prevention and treatment of osteoporosis. They are also used in other skeletal pathologies such as Paget's and metastatic bone disease. They effectively reduce osteoclast viability and also activity in the resorptive phase of bone remodelling and help preserve bone micro-architecture, both major determinants of bone strength and ultimately of the susceptibility to fractures. The chemically distinctive structure of each BP used in the clinic determines their unique affinity, distribution/penetration throughout the bone and their individual effects on bone geometry, micro-architecture and composition or what we call ‘bone quality'. BPs have no clinically significant anabolic effects. This review will touch upon some of the components of bone quality that could be affected by the administration of BPs.

The influence of hip rotation on femoral offset in plain radiographs.

Abstract: Background and purpose — Adequate restoration of femoral offset (FO) is critical for successful outcome after hip arthroplasty or fixation of hip fracture. Previous studies have identified that hip rotation influences the projected femoral offset (FOP) on plain anteroposterior (AP) radiographs, but the precise effect of rotation is unknown. Patients and methods — We developed a novel method of assessing rotation-corrected femoral offset (FORC), tested its clinical application in 222 AP hip radiographs following proximal femoral nailing, and validated it in 25 cases with corresponding computed tomography (CT) scans. Results — The mean FORC was 57 (29–93) mm, which differed significantly (p < 0.001) from the mean FOP 49 (22–65) mm and from the mean femoral offset determined by the standard method: 49 (23–66) mm. FORC correlated closely with femoral offset assessed by CT (FOCT); the Spearman correlation coefficient was 0.94 (95% CI: 0.88–0.97). The intraclass correlation coefficient for the assessment of FOR...

Living with a symptomatic rotator cuff tear ‘bad days, bad nights’: a qualitative study

Abstract: Rotator cuff tears are a common cause of shoulder pain. There is an absence of information about symptomatic rotator cuffs from the patients’ perspective; this limits the information clinicians can share with patients and the information that patients can access via sources such as the internet. This study describes the experiences of people with a symptomatic rotator cuff, their symptoms, the impact upon their daily lives and the coping strategies utilised by study participants. An interpretive phenomenological analysis approach was used. 20 participants of the UKUFF trial (The United Kingdom Rotator Cuff Surgery Trial) agreed to participate in in-depth semi-structured interviews about their experiences about living with a symptomatic rotator cuff tear. Interviews were digitally recorded and fully transcribed. Field notes, memos and a reflexive diary were used. Data was coded in accordance with interpretive phenomenological analysis. Peer review, code-recode audits and constant comparison of data, codes and categories occurred throughout. The majority of patients described intense pain and severely disturbed sleep. Limited movement and reduced muscle strength were described by some participants. The predominantly adverse impact that a symptomatic rotator cuff tear had upon activities of daily living, leisure activities and occupation was described. The emotional and financial impact and impact upon caring roles were detailed. Coping strategies included attempting to carry on as normally as possible, accepting their condition, using their other arm, using analgesics, aids and adaptions. Clinicians need to appreciate and understand the intensity and shocking nature of pain that may be experienced by participants with known rotator cuff tears and understand the detrimental impact tears can have upon all areas of patient’s lives. Clinicians also need to be aware of the potential emotional impact caused by cuff tears and to ensure that patients needing help for conditions such as depression are speedily identified and provided with support, explanation and appropriate treatment.

Advances in the diagnosis of degenerated lumbar discs and their possible clinical application.

Abstract: One possible source of chronic low back pain is a degenerated intervertebral disc. In this review, various diagnostic methods for the assessment of the presence of degenerative changes are described. These include clinical MRI, a number of novel MRI techniques and nuclear magnetic resonance spectroscopy. Non-systematic literature review. Clinical MRI is the most commonly employed technique to determine the general “health status” of the intervertebral disc. Novel MRI techniques, such as quantitative MRI, T1ρ MRI, sodium MRI and nuclear magnetic resonance spectroscopy, are more sensitive in quantifying the biochemical changes of disc degeneration, as measured by alteration in collagen structure, as well as water and proteoglycan loss. As potential future diagnostic alternatives, miniature sensors are currently being developed to measure parameters associated with the disc degeneration cascade, such as intradiscal pressure and PG concentration. However, none of the methods listed above show sufficient specificity to identify a degenerated disc as the actual source of the pain. Provocative discography is the only test aimed at a direct diagnosis of discogenic pain, but it has a high false positive rate and there is some evidence of long-term adverse effects. Imaging techniques have also been tested for this purpose, but their validity has not been confirmed and they do appear to be problematic. A reliable diagnostic tool that could help a clinician to determine if a disc is the source of the pain in patients with chronic LBP is still not available. New MRI techniques are under investigation that could result in a significant improvement over current methods, particularly as they can allow monitoring, not only of morphological but also of biochemical changes.

A meta‐ethnography of patients' experiences of chronic pelvic pain: struggling to construct chronic pelvic pain as ‘real’

Abstract: AIM: To review systematically and integrate the findings of qualitative research to increase our understanding of patients' experiences of chronic pelvic pain. BACKGROUND: Chronic pelvic pain is a prevalent pain condition with a high disease burden for men and women. Its multifactorial nature makes it challenging for clinicians and patients. DESIGN: Synthesis of qualitative research using meta-ethnography. DATA SOURCES: Five electronic bibliographic databases from inception until March 2014 supplemented by citation tracking. Of 488 papers retrieved, 32 met the review aim. REVIEW METHODS: Central to meta-ethnography is identifying 'concepts' and developing a conceptual model through constant comparison. Concepts are the primary data of meta-ethnography. Two team members read each paper to identify and collaboratively describe the concepts. We next compared concepts across studies and organized them into categories with shared meaning. Finally, we developed a conceptual model, or line of argument, to explain the conceptual categories. RESULTS: Our findings incorporate the following categories into a conceptual model: relentless and overwhelming pain; threat to self; unpredictability, struggle to construct pain as normal or pathological; a culture of secrecy; validation by diagnosis; ambiguous experience of health care; elevation of experiential knowledge and embodiment of knowledge through a community. CONCLUSION: The innovation of our model is to demonstrate, for the first time, the central struggle to construct 'pathological' vs. 'normal' chronic pelvic pain, a struggle that is exacerbated by a culture of secrecy. More research is needed to explore men's experience and to compare this with women's experience.

Imaging and management of greater trochanteric pain syndrome

Abstract: Greater trochanteric pain syndrome (GTPS) is a commonly diagnosed regional pain syndrome with a wide spectrum of aetiologies, reflecting the anatomy of the structures outside the hip joint capsule. There are five muscle tendons that insert on to the greater trochanter and three bursae in the region of the greater trochanter. The term GTPS includes tendinopathies, tendinous tears, bursal inflammation and effusion. There are a range of treatments and therapies depending on the specific diagnosis and severity of the condition. Many patients with GTPS can be successfully managed conservatively with weight loss and non-steroidal anti-inflammatory drugs. Patients suffering from more chronic pain can receive varying degrees of symptomatic relief with lateral hip corticosteroid and local anaesthetic injections. More severe refractory cases of GTPS can be treated with surgical intervention. It is therefore important to make the correct diagnosis to ensure that appropriate management can be implemented. The clinical features of GTPS however are often non-specific because common conditions such as lumbar radicular pain and hip joint osteoarthritis can present with an almost identical form of lateral hip pain. The various diagnostic imaging modalities have particular strengths and weaknesses with ultrasound being the best first-line investigation due to its availability, low cost, dynamic nature and ability to guide treatments such as steroid injections. MRI can be very helpful in the further investigation of patients in whom there is diagnostic uncertainty as to the cause of lateral hip pain and in whom specialist orthopaedic referral is being considered.

Predictive factors for successful clinical outcome 1 year after an intensive combined physical and psychological programme for chronic low back pain

Abstract: Purpose The aim of this longitudinal study is to determine the factors which predict a successful 1-year outcome from an intensive combined physical and psychological (CPP) programme in chronic low back pain (CLBP) patients.

Clinical guidelines in the management of prosthetic joint infection

Abstract: Clinical practice guidelines for the diagnosis and management of prosthetic joint infection have been produced by a range of organizations. Guidelines stress the importance of multi-disciplinary working and of adopting a methodical approach. This includes careful assessment of the patient's surgical, medical and psychosocial problems, rational investigation, a decision-making framework for surgery and targeted, sometimes prolonged, use of intravenous or highly bioavailable oral antibiotics. Despite limited high-quality evidence, adoption of clinical guidelines can improve practice by reducing variation and by establishing conditions for the subsequent conduct of multicentre studies or systematic reviews.

Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.

Abstract: Objective The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome-wide association studies (GWAS) enhances the power to detect additional loci. This study was undertaken to extend our previous RA GWAS in a UK cohort, adding more independent RA cases and healthy controls, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort. Methods A total of 3,223 UK RA cases and 5,272 UK controls were available for association analyses, with the extension adding 1,361 cases and 2,334 controls to the original GWAS data set. The genotype data for all RA cases were imputed using the Impute program version 2. After stringent quality control thresholds were applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide polymorphisms [SNPs]) were available for analysis. Association testing was performed using Plink software. Results The analyses indicated a suggestive association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have been previously found to be associated with other autoimmune diseases; these 6 SNPs were genotyped in independent samples. Two of the associated loci were validated, one of which was associated with RA at genome-wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 × 10−9). In addition, most of the previously known RA susceptibility loci were confirmed to be associated with RA, and for 16 of the loci, the strength of the association was increased. Conclusion This study identified a new RA locus mapping to 22q12. These results support the notion that increasing the power of GWAS enhances novel gene discovery.