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Showing papers by "Nuffield Orthopaedic Centre published in 2019"


Journal ArticleDOI
TL;DR: WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness.

372 citations


Journal ArticleDOI
21 Feb 2019-BMJ
TL;DR: TKA and UKA are both viable options for the treatment of isolated unicompartmental osteoarthritis by directly comparing the two treatments, and this study demonstrates better results for UKA in several outcome domains.
Abstract: Objective To present a clear and comprehensive summary of the published data on unicompartmental knee replacement (UKA) or total knee replacement (TKA), comparing domains of outcome that have been shown to be important to patients and clinicians to allow informed decision making. Design Systematic review using data from randomised controlled trials, nationwide databases or joint registries, and large cohort studies. Data sources Medline, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Clinical Trials.gov, searched between 1 January 1997 and 31 December 2018. Eligibility criteria for selecting studies Studies published in the past 20 years, comparing outcomes of primary UKA with TKA in adult patients. Studies were excluded if they involved fewer than 50 participants, or if translation into English was not available. Results 60 eligible studies were separated into three methodological groups: seven publications from six randomised controlled trials, 17 national joint registries and national database studies, and 36 cohort studies. Results for each domain of outcome varied depending on the level of data, and findings were not always significant. Analysis of the three groups of studies showed significantly shorter hospital stays after UKA than after TKA (−1.20 days (95% confidence interval −1.67 to −0.73), −1.43 (−1.53 to −1.33), and −1.73 (−2.30 to −1.16), respectively). There was no significant difference in pain, based on patient reported outcome measures (PROMs), but significantly better functional PROM scores for UKA than for TKA in both non-trial groups (standard mean difference −0.58 (−0.88 to −0.27) and −0.29 (−0.46 to −0.11), respectively). Regarding major complications, trials and cohort studies had non-significant results, but mortality after TKA was significantly higher in registry and large database studies (risk ratio 0.27 (0.16 to 0.45)), as were venous thromboembolic events (0.39 (0.27 to 0.57)) and major cardiac events (0.22 (0.06 to 0.86)). Early reoperation for any reason was higher after TKA than after UKA, but revision rates at five years remained higher for UKA in all three study groups (risk ratio 5.95 (1.29 to 27.59), 2.50 (1.77 to 3.54), and 3.13 (1.89 to 5.17), respectively). Conclusions TKA and UKA are both viable options for the treatment of isolated unicompartmental osteoarthritis. By directly comparing the two treatments, this study demonstrates better results for UKA in several outcome domains. However, the risk of revision surgery was lower for TKA. This information should be available to patients as part of the shared decision making process in choosing treatment options. Systematic review registration PROSPERO number CRD42018089972.

196 citations


Journal ArticleDOI
TL;DR: This review describes the incidence and pathophysiology of MRONJ, a rare, but potentially serious, adverse event associated with high cumulative doses of bisphosphonates or denosumab, and provides guidance for dental practitioners with regard to the screening, prophylactic treatment, diagnosis, and management of patients with this condition.
Abstract: Skeletal complications caused by osteoporosis or bone metastases are associated with considerable pain, increased mortality, and reduced quality of life. Furthermore, such events place a burden on health care resources. Agents that prevent bone resorption, such as bisphosphonates or denosumab, can reduce the risk of skeletal-related events and are widely used in patients with osteoporosis or bone metastases of cancer. Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but potentially serious, adverse event associated with high cumulative doses of bisphosphonates or denosumab. However, MRONJ can be treated, and the likelihood of the development of this condition can be reduced through prophylactic dental care and the maintenance of good oral hygiene. Dentists, as part of a multiprofessional team, have a critical role in preventing MRONJ. This review describes the incidence and pathophysiology of MRONJ and provides guidance for dental practitioners with regard to the screening, prophylactic treatment, diagnosis, and management of patients with this condition.

170 citations


Journal ArticleDOI
TL;DR: The short-term safety of immediate implant-based breast reconstruction performed with and without mesh is established, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques.
Abstract: Summary Background Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction—breast reconstruction with implants or expanders at the time of mastectomy—but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques. Methods In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281. Findings Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8–10) experienced implant loss, 372 (18%, 16–20) required re-admission to hospital, and 370 (18%, 16–20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23–27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards ( Interpretation Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction. Funding National Institute for Health Research, Association of Breast Surgery, and British Association of Plastic, Reconstructive and Aesthetic Surgeons.

129 citations


Journal ArticleDOI
TL;DR: Fifty years of research into the pharmacology of bisphosphonates have led to a fairly good understanding about how these drugs work and how they can be used safely in patients with metabolic bone diseases, but while the authors seemingly know much about these drugs, a number of key aspects related to BP distribution and action remain incompletely understood.
Abstract: The biological effects of the bisphosphonates (BPs) as inhibitors of calcification and bone resorption were first described in the late 1960s. In the 50 years that have elapsed since then, the BPs have become the leading drugs for the treatment of skeletal disorders characterized by increased bone resorption, including Paget's disease of bone, bone metastases, multiple myeloma, osteoporosis and several childhood inherited disorders. The discovery and development of the BPs as a major class of drugs for the treatment of bone diseases is a paradigm for the successful journey from "bench to bedside and back again". Several of the leading BPs achieved "blockbuster" status as branded drugs. However, these BPs have now come to the end of their patent life, making them highly affordable. The opportunity for new clinical applications for BPs also exists in other areas of medicine such as ageing, cardiovascular disease and radiation protection. Their use as inexpensive generic medicines is therefore likely to continue for many years to come. Fifty years of research into the pharmacology of bisphosphonates have led to a fairly good understanding about how these drugs work and how they can be used safely in patients with metabolic bone diseases. However, while we seemingly know much about these drugs, a number of key aspects related to BP distribution and action remain incompletely understood. This review summarizes the existing knowledge of the (pre)clinical and translational pharmacology of BPs, and highlights areas in which understanding is lacking.

101 citations


Journal ArticleDOI
TL;DR: Management strategies that solely target cardiovascular outcomes appear insufficient to improve the survival of patients with heart failure; the management of associated comorbidities, particularly infection prevention, appears as a major priority and opportunity.
Abstract: Importance Despite considerable improvements in heart failure care, mortality rates among patients in high-income countries have changed little since the early 2000s. Understanding the reasons underlying these trends may provide valuable clues for developing more targeted therapies and public health strategies. Objective To investigate mortality rates following a new diagnosis of heart failure and examine changes over time and by cause of death and important patient features. Design, Setting, and Participants This population-based retrospective cohort study analyzed anonymized electronic health records of individuals who received a new diagnosis of heart failure between January 2002 and December 2013 who were followed up until December 2014 from the Clinical Practice Research Datalink, which links information from primary care, secondary care, and the national death registry from a subset of the UK population. The data were analyzed from January 2018 to February 2019. Main Outcomes and Measures All-cause and cause-specific mortality rates at 1 year following diagnosis. Poisson regression models were used to calculate rate ratios (RRs) and 95% confidence intervals comparing 2013 with 2002, adjusting for age, sex, region, socioeconomic status, and 17 major comorbidities. Results Of 86 833 participants, 42 581 (49%) were women, 51 215 (88%) were white, and the mean (SD) age was 76.6 (12.6) years. While all-cause mortality rates declined only modestly over time (RR comparing 2013 with 2002, 0.94; 95% CI, 0.88-1.00), underlying patterns presented explicit trends. A decline in cardiovascular mortality (RR, 0.73; 95% CI, 0.67-0.80) was offset by an increase in noncardiovascular deaths (RR, 1.22; 95% CI, 1.11-1.33). Subgroup analyses further showed that overall mortality rates declined among patients younger than 80 years (RR, 0.79; 95% CI, 0.71-0.88) but not among those older than 80 years (RR, 0.97; 95% CI, 0.90-1.06). After cardiovascular causes (898 [43%]), the major causes of death in 2013 were neoplasms (311 [15%]), respiratory conditions (243 [12%]), and infections (13%), the latter 2 explaining most of the observed increase in noncardiovascular mortality. Conclusions and Relevance Among patients with a new heart failure diagnosis, considerable progress has been achieved in reducing mortality in young and middle-aged patients and cardiovascular mortality across all age groups. Improvements to overall mortality are hindered by high and increasing rates of noncardiovascular events. These findings challenge current research priorities and management strategies and call for a greater emphasis on associated comorbidities. Specifically, infection prevention presents as a major opportunity to improve prognosis.

82 citations


Journal ArticleDOI
TL;DR: This extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago.
Abstract: Standardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients. A comprehensive search was performed in all scientific literature since 1990. Studies in English that described surgical patient series for treatment of FRI were included. Data were collected on diagnostic criteria for FRI, classifications used, surgical treatments, follow-up protocols, and overall outcome. A systematic review was performed according to the PRISMA statement. Proportions and weighted means were calculated. The search yielded 2051 studies. Ninety-three studies were suitable for inclusion, describing 3701 patients (3711 fractures) with complex FRI. The population consisted predominantly of male patients (77%), with the tibia being the most commonly affected bone (64%), and a mean of three previous operations per patient. Forty-three (46%) studies described FRI at one specific location. Only one study (1%) used a standardized definition for infection. A total of nine different classifications were used to guide treatment protocols, of which Cierny and Mader was used most often (36%). Eighteen (19%) studies used a one-stage, 50 (54%) a two-stage, and seven (8%) a three-stage surgical treatment protocol. Ten studies (11%) used mixed protocols. Antibiotic protocols varied widely between studies. A multidisciplinary approach was mentioned in only 12 (13%) studies. This extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago. Internationally accepted guidelines are urgently required to improve the quality of care for patients suffering from this significant complication.

72 citations


Journal ArticleDOI
TL;DR: LA PJIs have a high failure rate and treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection.

68 citations


Journal ArticleDOI
TL;DR: The results of this in vitro study demonstrated that surgeons using this new surgical robot in total knee arthroplasty can perform highly accurate bone cuts to achieve the planned angles and resection thickness as measured using conventional navigation.
Abstract: Background Although the utility of robotic surgery has already been proven in cadaveric studies, it is our hypothesis that this newly designed robotically assisted system will achieve a high level of accuracy for bone resection. Therefore, we aimed to analyze in a cadaveric study the accuracy to achieve targeted angles and resection thickness. Methods For this study, 15 frozen cadaveric specimens (30 knees) were used. In this study, Zimmer Biomet (Warsaw, IN) knees, navigation system, and robot (ROSA Knee System; Zimmer Biomet) were used. Eight trained, board-certified orthopedic surgeons performed robotically assisted total knee arthroplasty implantation using the same robotic protocol with 3 different implant designs. The target angles obtained from the intraoperative planning were then compared to the angles of the bone cuts performed using the robotic system and measured with the computer-assisted system considered to be the gold standard. For each bone cut the resection thickness was measured 3 times by 2 different observers and compared to the values for the planned resections. Results All angle mean differences were below 1° and standard deviations below 1°. For all 6 angles, the mean differences between the target angle and the measured values were not significantly different from 0 except for the femoral flexion angle which had a mean difference of 0.95°. The mean hip-knee-ankle axis difference was −0.03° ± 0.87°. All resection mean differences were below 0.7 mm and standard deviations below 1.1mm. Conclusion Despite the fact that this study was funded by Zimmer Biomet and only used Zimmer Biomet implants, robot, and navigation tools, the results of our in vitro study demonstrated that surgeons using this new surgical robot in total knee arthroplasty can perform highly accurate bone cuts to achieve the planned angles and resection thickness as measured using conventional navigation.

68 citations


Journal ArticleDOI
TL;DR: There is sufficient evidence that multi-segment foot models may be successfully applied in clinical populations, according to major methodological issues discussed and relevant clinical applications analyzed.

64 citations


Journal ArticleDOI
TL;DR: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation.
Abstract: Background Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting Twenty-six NHS hospitals. Participants Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Future work Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. Trial registration Current Controlled Trials ISRCTN91566927. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Journal ArticleDOI
TL;DR: The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases, and the EM is preferable to the CCI but only marginal gains should be expected from incorporatingComorbidities over a period longer than 1 year.
Abstract: Comorbidity measures, such as the Charlson Comorbidity Index (CCI) and Elixhauser Method (EM), are frequently used for risk-adjustment by healthcare researchers. This study sought to create CCI and EM lists of Read codes, which are standard terminology used in some large primary care databases. It also aimed to describe and compare the predictive properties of the CCI and EM amongst patients with hip fracture (and matched controls) in a large primary care administrative dataset. Two researchers independently screened 111,929 individual Read codes to populate the 17 CCI and 31 EM comorbidity categories. Patients with hip fractures were identified (together with age- and sex-matched controls) from UK primary care practices participating in the Clinical Practice Research Datalink (CPRD). The predictive properties of both comorbidity measures were explored in hip fracture and control populations using logistic regression models fitted with 30- and 365-day mortality as the dependent variables together with tests of equality for Receiver Operating Characteristic (ROC) curves. There were 5832 CCI and 7156 EM comorbidity codes. The EM improved the ability of a logistic regression model (using age and sex as covariables) to predict 30-day mortality (AUROC 0.744 versus 0.686). The EM alone also outperformed the CCI (0.696 versus 0.601). Capturing comorbidities over a prolonged period only modestly improved the predictive value of either index: EM 1-year look-back 0.645 versus 5-year 0.676 versus complete record 0.695 and CCI 0.574 versus 0.591 versus 0.605. The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases. The EM is preferable to the CCI but only marginal gains should be expected from incorporating comorbidities over a period longer than 1 year.

Journal ArticleDOI
01 Dec 2019-BMJ Open
TL;DR: This scoping review assesses the current methodology and clinical application of accelerometers and inertial measurement units for the evaluation of patient activity and functional recovery following knee arthroplasty.
Abstract: Objectives Wearable motion sensors are used with increasing frequency in the evaluation of gait, function and physical activity within orthopaedics and sports medicine. The integration of wearable technology into the clinical pathway offers the ability to improve post-operative patient assessment beyond the scope of current, questionnaire-based patient-reported outcome measures. This scoping review assesses the current methodology and clinical application of accelerometers and inertial measurement units for the evaluation of patient activity and functional recovery following knee arthroplasty. Design This is a systematically conducted scoping review following Joanna Briggs Institute methodology for scoping reviews and reported consulting the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews. A protocol for this review is registered with the Open Science Framework (https://osf.io/rzg9q). Data sources CINAHL, EMBASE, MEDLINE and Web of Science databases were searched for manuscripts published between 2008 and 2019. Eligibility criteria We included clinical studies reporting the use of any combination of accelerometers, pedometers or inertial measurement units for patient assessment at any time point following knee arthroplasty. Data extraction and synthesis Data extracted from manuscripts included patient demographics, sensor technology, testing protocol and sensor-based outcome variables. Results 45 studies were identified, including 2076 knee arthroplasty patients, 620 patients with end-stage osteoarthritis and 449 healthy controls. Primary aims of the identified studies included functional assessment, physical activity monitoring and evaluation of knee instability. Methodology varied widely between studies, with inconsistency in reported sensor configuration, testing protocol and output variables. Conclusions The use of wearable sensors in evaluation of knee arthroplasty procedures is becoming increasingly common and offers the potential to improve clinical understanding of recovery and rehabilitation. While current studies lack consistency, significant opportunity exists for the development of standardised measures and protocols for function and physical activity evaluation.

Journal ArticleDOI
TL;DR: People who experience chronic musculoskeletal pain are at greater risk ofBeing lonely, but at less risk of being socially isolated, according to this study.
Abstract: Introduction:Musculoskeletal pain is a prevalent health challenge for all age groups worldwide, but most notably in older adults Social isolation is the consequence of a decrease in social network

Journal ArticleDOI
TL;DR: Most adverse outcomes were reduced in ex-smokers, therefore smoking cessation should be encouraged before arthroplasty, and smokers had improvement in PROMs compared with preoperatively.
Abstract: Background and purpose — Smoking is a modifiable risk factor that may adversely affect postoperative outcomes. Healthcare providers are increasingly denying smokers access to total hip and knee art...

Journal ArticleDOI
TL;DR: In this centre, rates of MRSA osteomyelitis have fallen by two thirds, over the past 10 years, in line with the reducing rate ofMRSA bacteraemia nationally, and resistance patterns support the use of a glycopeptide with an aminoglycoside in local antibiotic therapy.

Journal ArticleDOI
TL;DR: In this paper, a task-concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1) was used to alleviate phantom limb pain (PLP) in amputees.
Abstract: Objective Phantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP-related disease mechanisms. Noninvasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. Although NIBS can alleviate neuropathic pain (including PLP), both disease and treatment mechanisms remain tenuous. Insight into the mechanisms underlying both PLP and NIBS-induced PLP relief is needed for future implementation of such treatment and generalization to related conditions. Methods We used a within-participants, double-blind, and sham-controlled design to alleviate PLP via task-concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1). To specifically influence missing hand signal processing, amputees performed phantom hand movements during anodal transcranial direct current stimulation. Brain activity was monitored using neuroimaging during and after NIBS. PLP ratings were obtained throughout the week after stimulation. Results A single session of intervention NIBS significantly relieved PLP, with effects lasting at least 1 week. PLP relief associated with reduced activity in the S1/M1 missing hand cortex after stimulation. Critically, PLP relief and reduced S1/M1 activity correlated with preceding activity changes during stimulation in the mid- and posterior insula and secondary somatosensory cortex (S2). Interpretation The observed correlation between PLP relief and decreased S1/M1 activity confirms our previous findings linking PLP with increased S1/M1 activity. Our results further highlight the driving role of the mid- and posterior insula, as well as S2, in modulating PLP. Lastly, our novel PLP intervention using task-concurrent NIBS opens new avenues for developing treatment for PLP and related pain conditions. ANN NEUROL 2019;85:59-73.


Journal ArticleDOI
TL;DR: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays, and Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients.
Abstract: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients.

Journal ArticleDOI
TL;DR: Leptin can initiate processes involved in IVD degeneration, and this effect is potentiated in an environment of existing degeneration and inflammation, suggesting a biochemical mechanism may underlie the link between obesity, intervertebral disc degenerations and low back pain.
Abstract: The aim of this study was to identify the effects of leptin upon the intervertebral disc (IVD) and to determine whether these responses are potentiated within an environment of existing degeneration. Obesity is a significant risk factor for low back pain (LBP) and IVD degeneration. Adipokines, such as leptin, are novel cytokines produced primarily by adipose tissue and have been implicated in degradative and inflammatory processes. Obese individuals are known to have higher concentrations of serum leptin, and IVD cells express leptin receptors. We hypothesise that adipokines, such as leptin, mediate a biochemical link between obesity, IVD degeneration and LBP. The bovine intervertebral disc was used as a model system to investigate the biochemical effects of obesity, mediated by leptin, upon the intervertebral disc. Freshly isolated cells, embedded in 3D alginate beads, were subsequently cultured under varying concentrations of leptin, alone or together with the pro-inflammatory cytokines TNF-α, IL-1β or IL-6. Responses in relation to production of nitric oxide, lactate, glycosaminoglycans and expression of anabolic and catabolic genes were analysed. Leptin influenced the cellular metabolism leading particularly to greater production of proteases and NO. Addition of leptin to an inflammatory environment demonstrated a marked deleterious synergistic effect with greater production of NO, MMPs and potentiation of pro-inflammatory cytokine production. Leptin can initiate processes involved in IVD degeneration. This effect is potentiated in an environment of existing degeneration and inflammation. Hence, a biochemical mechanism may underlie the link between obesity, intervertebral disc degeneration and low back pain. These slides can be retrieved under Electronic Supplementary Material.

Journal ArticleDOI
TL;DR: There was no difference in implant survival between groups, and although there was no consistent trend in postoperative OKS, the BMI 35+ group benefited the most from UKA, suggesting high BMI should not be considered to be a contraindication when UKA is used for appropriate indications.
Abstract: Some health providers ration knee arthroplasty on the basis of body mass index (BMI). There is no long-term data on the outcome of medial mobile-bearing unicompartmental knee arthroplasty (UKA) in different BMI groups. This study aimed to determine the effect of patient body mass index (BMI) on patient-reported outcomes and long-term survival of medial UKA in a large non-registry cohort. Our hypothesis is that increasing BMI would be associated with worse outcomes. Data were analysed from a prospective cohort of 1000 consecutive medial mobile-bearing Oxford UKA with mean 10-year follow-up. Patients were grouped: BMI < 25, BMI 25 to < 30, BMI 30 to < 35 and BMI 35+. Oxford Knee Score (OKS) and Tegner Activity Score were assessed at 1, 5 and 10 years. Kaplan–Meier survivorship was calculated and compared between BMI groups. All groups had significant improvement in OKS and Tegner scores. BMI 35 + kg/m2 experienced the greatest overall increase in mean OKS of 17.3 points (p = 0.02). There was no significant difference in ten-year survival, which was, from lowest BMI group to highest 92%, 95%, 94% and 93%. There was no difference in implant survival between groups, and although there was no consistent trend in postoperative OKS, the BMI 35+ group benefited the most from UKA. Therefore, when UKA is used for appropriate indications, high BMI should not be considered to be a contraindication. Furthermore rationing based on BMI seems unjustified, particularly when the commonest threshold (BMI 35) is used. III.

Journal ArticleDOI
TL;DR: Investigating whether statin use is associated with a lower risk of radiographic OA (ROA), radiographic symptomatic knee OA, and pain in North American individuals found it to be so.
Abstract: Objective Statins have several pleiotropic effects, but the literature regarding the possible relationship between use of statins and outcomes in knee osteoarthritis (OA) is limited. The aim of this study was to investigate whether statin use is associated with a lower risk of radiographic OA (ROA), radiographic symptomatic knee OA, and pain in North American individuals. Methods A total of 4,448 community-dwelling adults from the Osteoarthritis Initiative were followed for 4 years. Statin use (including the time from baseline and the type of statin) was defined through self-report information and confirmed by a trained interviewer. Knee OA outcomes included incident ROA, symptomatic knee OA (new onset of a combination of a painful knee and ROA), and knee pain worsening (i.e., a Western Ontario and McMaster Universities Osteoarthritis Index difference between baseline and each annual examination ≥14%). Results At baseline, 1,127 participants (25.3% of the total population) used statins. Based on a multivariable Poisson regression analysis with robust variance estimators, any use of statins was not associated with a lower risk of pain worsening (relative risk [RR] 0.97, 95% confidence interval [95% CI] 0.93-1.02), incident ROA, or symptomatic knee OA. However, statin use for more than 5 years (RR 0.91, 95% CI 0.83-0.997) and use of atorvastatin (RR 0.95, 95% CI 0.91-0.996) were associated with a reduced risk of developing pain, while rosuvastatin use was associated with a higher risk (RR 1.18, 95% CI 1.12-1.24). Analysis with adjustment for the propensity score confirmed these findings. Conclusion The effect of statin use on knee OA outcomes remains unclear, although in our study, a significantly lower risk of developing knee pain was observed in individuals using statins for >5 years and those using atorvastatin.

Journal ArticleDOI
TL;DR: DAIR is a viable surgical treatment for most patients with LA PJI, but implant removal should be considered in a subset of patients, especially in those with a CRIME80-score ≥3, as well as independent predictors for failure in the multivariate analysis.

Journal ArticleDOI
TL;DR: The imaging findings and diagnostic utility of plain radiographs, ultrasound, DECT, MRI and nuclear medicine studies in the assessment as well as the implications and utility these tools have for measuring disease burden and therapeutic response are summarized.
Abstract: The plain radiographic features of gout are well known; however, the sensitivity of plain radiographs alone for the detection of signs of gout is poor in acute disease. Radiographic abnormalities do not manifest until late in the disease process, after significant joint and soft tissue damage has already occurred. The advent of dual-energy computed tomography (DECT) has enabled the non-invasive diagnosis and quantification of gout by accurately confirming the presence and extent of urate crystals in joints and soft tissues, without the need for painful and often unreliable soft tissue biopsy or joint aspiration. Specific ultrasound findings have been identified and may also be used to aid diagnosis. Both ultrasound and magnetic resonance imaging (MRI) may be used for the measurement of disease extent, monitoring of disease activity or treatment response, although MRI findings are nonspecific. In this article we summarize the imaging findings and diagnostic utility of plain radiographs, ultrasound, DECT, MRI and nuclear medicine studies in the assessment as well as the implications and utility these tools have for measuring disease burden and therapeutic response.

Journal ArticleDOI
16 Mar 2019
TL;DR: In this article, the authors assess radiographic bone healing following implantation of a gentamicin-eluting synthetic bone graft substitute (gBGS) used at chronic osteomyelitis (cOM) resection.
Abstract: Introduction: Managing chronic osteomyelitis can be challenging and attention to the osseous dead-space left following resection is an important part of successful treatment. We assess radiographic bone healing following implantation of a gentamicin-eluting synthetic bone graft substitute (gBGS) used at chronic osteomyelitis (cOM) resection. We also describe histological carrier changes from biopsies in nine cases at various time points. Methods: This was a retrospective review of a prospectively collected consecutive series of 163 patients with Cierny-Mader Type III or IV cOM who underwent single-stage excision, insertion of gBGS and definitive soft-tissue closure or coverage. Bone defect filling was assessed radiographically using serial radiographs. Nine patients had subsequent surgery, not related to infection recurrence, allowing opportunistic biopsy between 19 days and two years after implantation. Results: Infection was eradicated in 95.7% with a single procedure. 138 patients had adequate radiographs for assessment with minimum one-year follow-up (mean 1.7 years, range 1.0-4.7 years). Mean void-filling at final follow-up was 73.8%. There was significantly higher void-filling in metaphyseal compared to diaphyseal voids (mean 79.0% versus 65.6%; p=0.017) and in cases with good initial interdigitation of the carrier (mean 77.3% versus 68.7%; p=0.021). Bone formation continued for more than two years in almost two-thirds of patients studied (24/38; 63.2%). Histology revealed active biomaterial remodelling. It was osteoconductive with osteoblast recruitment, leading to the formation of osteoid, then woven and lamellar bone on the substrate's surface. Immunohistochemistry demonstrated osteocyte specific markers, dentine matrix protein-1 and podoplanin within the newly formed bone. Conclusion: This antibiotic-loaded biomaterial is effective in managing dead-space in surgically treated cOM with a low infection recurrence rate (4.3%) and good mean bone void-filling (73.8%). The radiographic resolution of the bone defect is associated with bone formation, as supported by histological analysis.

Journal ArticleDOI
09 Dec 2019-Trials
TL;DR: A treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection is assessed, and this will be to the advantage of patients and contribute to antimicrobial stewardship.
Abstract: Orthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4–6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance. SOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis. This study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship. Clinicaltrials.gov, NCT03806166. Registered on 11 November 2019.

Journal ArticleDOI
TL;DR: A pictorial review describes the full imaging workup and pathway of suspected brown tumour in the setting of both primary and secondary hyperparathyroidism and highlights the complementary roles that different imaging modalities can play in different settings.
Abstract: Brown tumours do not represent neoplastic process, but they are focal bony lesions due to bone remodelling from either primary or secondary hyperparathyroidism. Their incidence is also low. The current literature on brown tumour is mainly in the form of case reports that focus on single affected sites. This pictorial review describes the full imaging workup and pathway of suspected brown tumour in the setting of both primary and secondary hyperparathyroidism. It aims to illustrate the management strategy to aid both clinicians and radiologists in suspected cases of brown tumour. We highlight the complementary roles that different imaging modalities can play in different settings including the importance of parathyroid ultrasound, 99mTc-sestamibi scintigraphy and SPECT/CT in the localisation of the parathyroid adenoma. We present cases with full clinical and imaging workup in both the acute and chronic setting and scenarios that require exclusion of primary and secondary bone malignancies.

Journal ArticleDOI
TL;DR: The best management of periprosthetic elbow infection is difficult to determine, but two-stage revision appears to be the gold standard.
Abstract: BackgroundThe aim of this scoping review is to assess the current evidence regarding periprosthetic shoulder infection to inform development of evidence and consensus-based guidelinesMethodsA sear

Journal ArticleDOI
06 Feb 2019
TL;DR: A conceptual model underpinned by living life precariously with rheumatoid arthritis is developed that has some important clinical implications that might be transferable to other musculoskeletal conditions.
Abstract: Rheumatoid arthritis is an autoimmune disease that causes joint inflammation. It affects around 400,000 people in the UK and 1 million adults in the USA. Given the appropriate treatment, many can have relatively few symptoms. It is therefore important to understand what it is like to live with rheumatoid arthritis and gain insight into peoples’ decisions about utilising healthcare. The aims of this study were: (1) to bring together qualitative evidence syntheses that explore patients’ experience of living with rheumatoid arthritis and (2) develop a conceptual understanding of what it is like to live with rheumatoid arthritis. We used the methods of mega-ethnography. The innovation of mega-ethnography is to use conceptual findings from qualitative evidence syntheses as primary data. We searched four bibliographic databases from inception until September 2018 to identify qualitative evidence syntheses that explored patients’ experience of rheumatoid arthritis. We identified 373 qualitative evidence syntheses, removed 179 duplicates and screened 194 full text studies. We identified 42 qualitative evidence syntheses that explored the experience of pain or arthritis and 9 of these explored the experience of rheumatoid arthritis. We abstracted ideas into 10 conceptual categories: (1) rheumatoid arthritis is in control of my body (2) rheumatoid arthritis alters reciprocity; (3) rheumatoid arthritis is an emotional challenge; (4) rheumatoid arthritis disrupts my present and future self; (5) the challenge of balancing personal and work life; (6) I am trying to make sense of what is happening; (7) rheumatoid arthritis is variable and unpredictable; (8) rheumatoid arthritis is invisible; (9) I need a positive experience of healthcare, and (10) I need to reframe the situation. We developed a conceptual model underpinned by living life precariously with rheumatoid arthritis. This is the second mega-ethnography, or synthesis of qualitative evidence syntheses using the methods of meta-ethnography. Future research should consider the proliferation of qualitative evidence synthesis in order to avoid duplication of research effort. Our model for rheumatoid arthritis has some important clinical implications that might be transferable to other musculoskeletal conditions.

Journal ArticleDOI
11 Sep 2019-BMJ Open
TL;DR: The available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator, and there is a need for a large, methodologically robust RCT investigating the commonly use injection therapies and comparing them with other therapeutic options and placebo.
Abstract: Objective To evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis. Design Systematic review and meta-analysis. Data sources MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018. Study selection Randomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s. Data extraction and analysis Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up. Results In total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) −1.32, 95% CI −2.23 to −0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator. Conclusion Current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo. PROSPERO registration number CRD42018095384.