Aims. Systematic reviews of randomized controlled trials (RCTs) are the highest level of evidence used to inform patient care. However, it has been suggested that the quality of randomization in RCTs in orthopaedic surgery may be low. This study aims to describe the quality of randomization in trials included in systematic reviews in orthopaedic surgery. Methods. Systematic reviews of RCTs testing orthopaedic procedures published in 2022 were extracted from PubMed, Embase, and the Cochrane Library. A random sample of 100 systematic reviews was selected, and all included RCTs were retrieved. To be eligible for inclusion, systematic reviews must have tested an orthopaedic procedure as the primary intervention, included at least one study identified as a RCT, been published in 2022 in English, and included human clinical trials. The Cochrane Risk of Bias-2 Tool was used to assess random sequence generation as ‘adequate’, ‘inadequate’, or ‘no information’; we then calculated the proportion of trials in each category. We also collected data to test the association between these categories and characteristics of the RCTs and systematic reviews. Results. We included 917 unique RCTs. We found that 374 RCTs (40.8%) reported adequate sequence generation, 61 (6.7%) were inadequate, 410 (44.7%) lacked information, and 72 (7.9%) were observational studies incorrectly included as RCTs within the systematic review. Publication year, an author with statistical or epidemiological qualifications, and journal impact factor were each associated with adequate randomization. We found that 45 systematic reviews (45%) included at least one inadequately randomized RCT or an observational study incorrectly treated as a RCT. Conclusion. There is evidence of a lack of random allocation in RCTs included in systematic reviews in orthopaedic surgery. The conduct of RCTs and systematic reviews should be improved to minimize the risk of bias from inadequate randomization in RCTs and mislabelling of non-randomized studies as RCTs. Cite this article: Bone Jt Open 2024;5(12):1072–1080

The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs. Cite this article: Bone Joint Res 2014;3:169–74

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding. Cite this article: Bone Joint Res 2014;3:161–8

It is unusual, if not unique, for three major research papers concerned with the management of the fractured neck of femur (FNOF) to be published in a short period of time, each describing large prospective randomized clinical trials. These studies were conducted in up to 17 countries worldwide, involving up to 80 surgical centers and include large numbers of patients (up to 2,900) with FNOF. Each article investigated common clinical dilemmas; the first paper comparing total hip arthroplasty versus hemiarthroplasty for FNOF, the second as to whether ‘fast track’ care offers improved clinical outcomes and the third, compares sliding hip with multiple cancellous hip screws. Each paper has been deemed of sufficient quality and importance to warrant publication in The Lancet or the New England Journal of Medicine. Although ‘premier’ journals, they only occationally contain orthopaedic studies and thus may not be routinely read by the busy orthopaedic/surgical clinician of any grade. It is therefore our intention with this present article to accurately summarize and combine the results of all three papers, presenting, in our opinion, the most important clinically relevant facts. Cite this article: Bone Joint Open 2020;1-6:198–202

Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework – a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.

Cite this article: Bone Joint Res 2024;13(9):507–512.

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses. Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure. In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future. Cite this article: Bone Joint J 2014;96-B:291–8

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications. Cite this article: Bone Joint J 2015; 97-B:582–9

Aims

Patient-reported outcome measures have become an important part of routine care. The aim of this study was to determine if Patient-Reported Outcomes Measurement Information System (PROMIS) measures can be used to create patient subgroups for individuals seeking orthopaedic care.

Aims

The aim of this study was to investigate surgeons’ reported change of treatment preference in response to the results and conclusion from a randomized contolled trial (RCT) and to study patterns of change between subspecialties and nationalities.

Aim

The coronavirus disease 2019 (COVID-19) pandemic presents significant challenges to healthcare systems globally. Orthopaedic surgeons are at risk of contracting COVID-19 due to their close contact with patients in both outpatient and theatre environments. The aim of this review was to perform a literature review, including articles of other coronaviruses, to formulate guidelines for orthopaedic healthcare staff.

Introduction

There is widespread variation in the management of rare orthopaedic disease, in a large part owing to uncertainty. No individual surgeon or hospital is typically equipped to amass sufficient numbers of cases to draw robust conclusions from the information available to them. The programme of research will establish the British Orthopaedic Surgery Surveillance (BOSS) Study; a nationwide reporting structure for rare disease in orthopaedic surgery.

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO.

This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

Cite this article: Bone Joint J 2015;97-B:572–6

Objectives

Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA).

There has been an in increase in the availability of effective biological agents for the treatment of rheumatoid arthritis as well as a shift towards early diagnosis and management of the inflammatory process. This article explores the impact this may have on the place of orthopaedic surgery in the management of patients with rheumatoid arthritis.

Cite this article: Bone Joint J 2014;96-B:1287–9

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes.

Cite this article: Bone Joint J 2014;96-B:1561–5.

The contemporary practice of orthopaedic surgery requires an evidence-based approach to support all medical and surgical interventions. In this essay, the author expresses a forthright, personal and somewhat prejudiced appeal to retain the legitimacy of clinical decision making in conditions that are rare, contain multiple variables, have a solution that generally works or has an unpredictable course.

Cite this article: Bone Joint J 2014;96-B:1002–4.

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions.

Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation.

Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future.

Cite this article: Bone Joint J 2014; 96-B: 569–73.

In May 2012, in airports across the globe, seven orthopaedic surgeons bravely said goodbye to their loved ones, and slowly turned towards their respective aircraft. Filled with expectation and mild trepidation they stepped into the unknown… the ABC fellowship of 2012.

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition.

Cite this article: Bone Joint J 2013;95-B:738–46.

The most frequent cause of failure after total hip replacement in all reported arthroplasty registries is peri-prosthetic osteolysis. Osteolysis is an active biological process initiated in response to wear debris. The eventual response to this process is the activation of macrophages and loss of bone.

Activation of macrophages initiates a complex biological cascade resulting in the final common pathway of an increase in osteolytic activity. The biological initiators, mechanisms for and regulation of this process are beginning to be understood. This article explores current concepts in the causes of, and underlying biological mechanism resulting in peri-prosthetic osteolysis, reviewing the current basic science and clinical literature surrounding the topic.

Using inaccurate quotations can propagate misleading information, which might affect the management of patients. The aim of this study was to determine the predictors of quotation inaccuracy in the peer-reviewed orthopaedic literature related to the scaphoid. We randomly selected 100 papers from ten orthopaedic journals. All references were retrieved in full text when available or otherwise excluded. Two observers independently rated all quotations from the selected papers by comparing the claims made by the authors with the data and expressed opinions of the reference source. A statistical analysis determined which article-related factors were predictors of quotation inaccuracy. The mean total inaccuracy rate of the 3840 verified quotes was 7.6%. There was no correlation between the rate of inaccuracy and the impact factor of the journal. Multivariable analysis identified the journal and the type of study (clinical, biomechanical, methodological, case report or review) as important predictors of the total quotation inaccuracy rate.

We concluded that inaccurate quotations in the peer-reviewed orthopaedic literature related to the scaphoid were common and slightly more so for certain journals and certain study types. Authors, reviewers and editorial staff play an important role in reducing this inaccuracy.

Painful neuromas may follow traumatic nerve injury. We carried out a double-blind controlled trial in which patients with a painful neuroma of the lower limb (n = 20) were randomly assigned to treatment by resection of the neuroma and translocation of the proximal nerve stump into either muscle tissue or an adjacent subcutaneous vein. Translocation into a vein led to reduced intensity of pain as assessed by visual analogue scale (5.8 (sd 2.7) vs 3.8 (sd 2.4); p < 0.01), and improved sensory, affective and evaluative dimensions of pain as assessed by the McGill pain score (33 (sd 18) vs 14 (sd 12); p < 0.01). This was associated with an increased level of activity (p < 0.01) and improved function (p < 0.01).

Transposition of the nerve stump into an adjacent vein should be preferred to relocation into muscle.

Over a 13-year period we studied all patients who underwent major hip and knee surgery and were diagnosed with objectively confirmed symptomatic venous thromboembolism, either deep venous thrombosis or non-fatal pulmonary embolism, within six months after surgery. Low-molecular-weight heparin had been given while the patients were in hospital.

There were 5607 patients. The cumulative incidence of symptomatic venous thromboembolism was 2.7% (150 of 5607), of which 1.1% had developed pulmonary embolism, 1.5% had deep venous thrombosis and 0.6% had both. Patients presented with deep venous thrombosis at a median of 24 days and pulmonary embolism at 17 days after surgery for hip fracture. After total hip replacement, deep venous thrombosis and pulmonary embolism occurred at a median of 21 and 34 days respectively. After total knee replacement, the median time to the presentation of deep venous thrombosis and pulmonary embolism was 20 and 12 days respectively. The cumulative risk of venous thromboembolism lasted for up to three months after hip surgery and for one month after total knee replacement. Venous thromboembolism was diagnosed after discharge from hospital in 70% of patients who developed this complication.

Despite hospital-based thromboprophylaxis, most cases of clinical venous thromboembolism occur after discharge and at different times according to the operation performed.

The Department of Health and the Public Health Laboratory Service established the Nosocomial Infection National Surveillance Scheme in order to standardise the collection of information about infections acquired in hospital in the United Kingdom and provide national data with which hospitals could measure their own performance. The definition of superficial incisional infection (skin and subcutaneous tissue), set by the Center for Disease Control (CDC), should meet at least one of the defined criteria which would confirm the diagnosis and determine the need for specific treatment.

We have assessed the interobserver reliability of the criteria for superficial incisional infection set by the CDC in our current practice. The incisional site of 50 patients who had an elective primary arthroplasty of the hip or knee was evaluated independently by two orthopaedic clinical research fellows and two orthopaedic ward sisters for the presence or absence of surgical-site infection. Interobserver reliability was assessed by comparison of the criteria for wound infection used by the four observers using kappa reliability coefficients. Our study demonstrated that some of the components of the current CDC criteria were unreliable and we recommend their revision.

We have prospectively studied the outcome of infections associated with implants which were retained and treated using a standardised antimicrobial protocol. Over a period of four years, we studied 24 consecutive patients who had symptoms of infection for less than one year, a stable implant, no sinus tract and a known pathogen which was susceptible to recommended antimicrobial agents. The infections involved hip prostheses (14), knee prostheses (5), an internal fixation device (4), and an ankle prosthesis (1).

Twenty patients had a successful outcome at a median follow-up of 3.7 years (1.8 to 4.7); four had failure of the implant after a median follow-up of 1.2 years (0.3 to 2.5). The probability of survival without failure of treatment was 96% at one year (95% confidence interval (CI) 88 to 100), 92% at two years (95% CI 80 to 100) and 86% at three years (95% CI 72 to 100).

Patients with a short-term infection but with a stable implant, no sinus tract and a known pathogen may be successfully treated by retention of the implant and the use of a standardised regimen of antimicrobial treatment.