Aims. Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484

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

Aims. This systematic review places a recently completed multicentre randomized controlled trial (RCT), UK FROST, in the context of existing randomized evidence for the management of primary frozen shoulder. UK FROST compared the effectiveness of pre-specified physiotherapy techniques with a steroid injection (PTSI), manipulation under anaesthesia (MUA) with a steroid injection, and arthroscopic capsular release (ACR). This review updates a 2012 review focusing on the effectiveness of MUA, ACR, hydrodilatation, and PTSI. Methods. MEDLINE, Embase, PEDro, Science Citation Index, Clinicaltrials.gov, CENTRAL, and the World Health Organization (WHO) International Clinical Trials Registry were searched up to December 2018. Reference lists of included studies were screened. No language restrictions applied. Eligible studies were RCTs comparing the effectiveness of MUA, ACR, PTSI, and hydrodilatation against each other, or supportive care or no treatment, for the management of primary frozen shoulder. Results. Nine RCTs were included. The primary outcome of patient-reported shoulder function at long-term follow-up (> 6 months and ≤ 12 months) was reported for five treatment comparisons across four studies. Standardized mean differences (SMD) were: ACR versus MUA: 0.21 (95% confidence interval (CI) 0.00 to 0.42), ACR versus supportive care: -0.13 (95% CI -1.10 to 0.83), and ACR versus PTSI: 0.33 (95% CI 0.07 to 0.59) and 0.25 (95% CI -0.34 to 0.85), all favouring ACR; MUA versus supportive care: 0 (95% CI -0.44 to 0.44) not favouring either; and MUA versus PTSI: 0.12 (95% CI -0.14 to 0.37) favouring MUA. None of these differences met the threshold of clinical significance agreed for the UK FROST and most confidence intervals included zero. Conclusion. The findings from a recent multicentre RCT provided the strongest evidence that, when compared with each other, neither PTSI, MUA, nor ACR are clinically superior. Evidence from smaller RCTs did not change this conclusion. The effectiveness of hydrodilatation based on four RCTs was inconclusive and there remains an evidence gap. Cite this article: Bone Jt Open 2021;2(9):773–784

Aims. Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Methods. Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. Results. No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. Conclusion. No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome. Cite this article: Bone Jt Open 2023;4(2):96–103

Aims. Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results. In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion. Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes. Cite this article: Bone Joint J 2024;106-B(6):532–539

Aims. The aim of this study was to determine the effectiveness of home-based prehabilitation on pre- and postoperative outcomes in participants awaiting total knee (TKA) and hip arthroplasty (THA). Methods. A systematic review with meta-analysis of randomized controlled trials (RCTs) of prehabilitation interventions for TKA and THA. MEDLINE, CINAHL, ProQuest, PubMed, Cochrane Library, and Google Scholar databases were searched from inception to October 2022. Evidence was assessed by the PEDro scale and the Cochrane risk-of-bias (ROB2) tool. Results. A total of 22 RCTs (1,601 patients) were identified with good overall quality and low risk of bias. Prehabilitation significantly improved pain prior to TKA (mean difference (MD) -1.02: p = 0.001), with non-significant improvements for function before (MD -0.48; p = 0.06) and after TKA (MD -0.69; p = 0.25). Small preoperative improvements were observed for pain (MD -0.02; p = 0.87) and function (MD -0.18; p = 0.16) prior to THA, but no post THA effect was found for pain (MD 0.19; p = 0.44) and function (MD 0.14; p = 0.68). A trend favouring usual care for improving quality of life (QoL) prior to TKA (MD 0.61; p = 0.34), but no effect on QoL prior (MD 0.03; p = 0.87) or post THA (MD -0.05; p = 0.83) was found. Prehabilitation significantly reduced hospital length of stay (LOS) for TKA (MD -0.43 days; p < 0.001) but not for THA (MD, -0.24; p = 0.12). Compliance was only reported in 11 studies and was excellent with a mean value of 90.5% (SD 6.82). Conclusion. Prehabilitation interventions improve pain and function prior to TKA and THA and reduce hospital LOS, though it is unclear if these effects enhance outcomes postoperatively. Cite this article: Bone Jt Open 2023;4(5):315–328

Aims. The aims of this network meta-analysis (NMA) were to examine nonunion rates and functional outcomes following various operative and nonoperative treatments for displaced mid-shaft clavicle fractures. Methods. Initial search strategy incorporated MEDLINE, PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs). Four treatment arms were created: nonoperative (NO); intramedullary nailing (IMN); reconstruction plating (RP); and compression/pre-contoured plating (CP). A Bayesian NMA was conducted to compare all treatment options for outcomes of nonunion, malunion, and function using the Disabilities of the Arm Shoulder and Hand (DASH) and Constant-Murley Shoulder Outcome scores. Results. In all, 19 RCTs consisting of 1,783 clavicle fractures were included in the NMA. All surgical options demonstrated a significantly lower odds ratio (OR) of nonunion in comparison to nonoperative management: CP versus NO (OR 0.08; 95% confidence interval (CI) 0.04 to 0.17); IMN versus NO (OR 0.07; 95% CI 0.02 to 0.19); RP versus NO (OR 0.07; 95% CI: 0.01 to 0.24). Compression plating was the only treatment to demonstrate significantly lower DASH scores relative to NO at six weeks (mean difference -10.97; 95% CI -20.69 to 1.47). Conclusion. Surgical fixation demonstrated a lower risk of nonunion compared to nonoperative management. Compression plating resulted in significantly less disability early after surgery compared to nonoperative management. These results demonstrate possible early improved functional outcomes with compression plating compared to nonoperative treatment. Surgical fixation of mid-shaft clavicle fractures with compression plating may result in quicker return to activity by rendering patients less disabled early after surgery. Cite this article: Bone Jt Open 2021;2(8):646–654

Aims. To explore staff experiences of a multicentre pilot randomized controlled trial (RCT) comparing intramedullary nails and circular frame external fixation for segmental tibial fractures. Methods. A purposeful sample of 19 staff (nine surgeons) involved in the study participated in an interview. Interviews explored participants’ experience and views of the study and the treatments. The interviews drew on phenomenology, were face-to-face or by telephone, and were analyzed using thematic analysis. Results. The findings identify that for the treatment of segmental tibial fractures equipoise was a theoretical ideal that was most likely unattainable in clinical practice. This was conveyed through three themes: the ambiguity of equipoise, where multiple definitions of equipoise and a belief in community equipoise were evident; an illusion of equipoise, created by strong treatment preferences and variation in collective surgical skills; and treating the whole patient, where the complexity and severity of the injury required a patient-centred approach and doing the best for the individual patient took priority over trial recruitment. Conclusion. Equipoise can be unattainable for rare injuries such as segmental tibial fractures, where there are substantially different surgical treatments requiring specific expertise, high levels of complexity, and a concern for poor outcomes. Surgeons are familiar with community equipoise. However, a shared understanding of factors that limit the feasibility of RCTs may identify instances where community equipoise is unlikely to translate into practice. Cite this article: Bone Jt Open 2021;2(7):486–492

Aims. Many surgeons choose to perform total knee arthroplasty (TKA) surgery with the aid of a tourniquet. A tourniquet is a device that fits around the leg and restricts blood flow to the limb. There is a need to understand whether tourniquets are safe, and if they benefit, or harm, patients. The aim of this study was to determine the benefits and harms of tourniquet use in TKA surgery. Methods. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, and trial registries up to 26 March 2020. We included randomized controlled trials (RCTs), comparing TKA with a tourniquet versus without a tourniquet. Outcomes included: pain, function, serious adverse events (SAEs), blood loss, implant stability, duration of surgery, and length of hospital stay. Results. We included 41 RCTs with 2,819 participants. SAEs were significantly more common in the tourniquet group (53/901 vs 26/898, tourniquet vs no tourniquet respectively) (risk ratio 1.73 (95% confidence interval (CI) 1.10 to 2.73). The mean pain score on the first postoperative day was 1.25 points higher (95% CI 0.32 to 2.19) in the tourniquet group. Overall blood loss did not differ between groups (mean difference 8.61 ml; 95% CI -83.76 to 100.97). The mean length of hospital stay was 0.34 days longer in the group that had surgery with a tourniquet (95% CI 0.03 to 0.64) and the mean duration of surgery was 3.7 minutes shorter (95% CI -5.53 to -1.87). Conclusion. TKA with a tourniquet is associated with an increased risk of SAEs, pain, and a marginally longer hospital stay. The only finding in favour of tourniquet use was a shorter time in theatre. The results make it difficult to justify the routine use of a tourniquet in TKA surgery. Cite this article: Bone Joint J 2021;103-B(5):830–839

Aims. The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease. Methods. A systematic search was performed on PubMed, EMBASE, the Cochrane Library, MEDLINE, China National Knowledge Infrastructure (CNKI), and WANFANG for randomized controlled trials (RCTs) that investigated the safety and accuracy of RA compared with conventional freehand with/without fluoroscopy-assisted pedicle screw insertion for spine disease from 2012 to 2019. This meta-analysis used Mantel-Haenszel or inverse variance method with mixed-effects model for heterogeneity, calculating the odds ratio (OR), mean difference (MD), standardized mean difference (SMD), and 95% confidence intervals (CIs). The results of heterogeneity, subgroup analysis, and risk of bias were analyzed. Results. Ten RCTs with 713 patients and 3,331 pedicle screws were included. Compared with CT, the accuracy rate of RA was superior in Grade A with statistical significance and Grade A + B without statistical significance. Compared with CT, the operating time of RA was longer. The difference between RA and CT was statistically significant in radiation dose. Proximal facet joint violation occurred less in RA than in CT. The postoperative Oswestry Disability Index (ODI) of RA was smaller than that of CT, and there were some interesting outcomes in our subgroup analysis. Conclusion. RA technique could be viewed as an accurate and safe pedicle screw implantation method compared to CT. A robotic system equipped with optical intraoperative navigation is superior to CT in accuracy. RA pedicle screw insertion can improve accuracy and maintain stability for some challenging areas. Cite this article: Bone Joint Res 2020;9(10):653–666

Objectives. The objective of this study was to perform a meta-analysis of all randomised controlled trials (RCTs) comparing surgical and non-surgical management of fractures of the proximal humerus, and to determine whether further analyses based on complexity of fracture, or the type of surgical intervention, produced disparate findings on patient outcomes. Methods. A systematic review of the literature was performed identifying all RCTs that compared surgical and non-surgical management of fractures of the proximal humerus. Meta-analysis of clinical outcomes was performed where possible. Subgroup analysis based on the type of fracture, and a sensitivity analysis based on the type of surgical intervention, were also performed. Results. Seven studies including 528 patients were included. The overall meta-analysis found that there was no difference in clinical outcomes. However, subgroup and sensitivity analyses found improved patient outcomes for more complex fractures managed surgically. Four-part fractures that underwent surgery had improved long-term health utility scores (mean difference, MD 95% CI 0.04 to 0.28; p = 0.007). They were also less likely to result in osteoarthritis, osteonecrosis and non/malunion (OR 7.38, 95% CI 1.97 to 27.60; p = 0.003). Another significant subgroup finding was that secondary surgery was more common for patients that underwent internal fixation compared with conservative management within the studies with predominantly three-part fractures (OR 0.15, 95% CI 0.04 to 0.63; p = 0.009). Conclusion. This meta-analysis has demonstrated that differences in the type of fracture and surgical treatment result in outcomes that are distinct from those generated from analysis of all types of fracture and surgical treatments grouped together. This has important implications for clinical decision making and should highlight the need for future trials to adopt more specific inclusion criteria. Cite this article: S. Sabharwal, N. K. Patel, D. Griffiths, T. Athanasiou, C. M. Gupte, P. Reilly. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus: Findings of a meta-analysisBone Joint Res 2016;5:470–480. DOI: 10.1302/2046-3758.510.2000638

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

Objectives. Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. Materials and Methods. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. Results. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Conclusions. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA. Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2

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Hand trauma, consisting of injuries to both the hand and the wrist, are a common injury seen worldwide. The global age-standardized incidence of hand trauma exceeds 179 per 100,000. Hand trauma may require surgical management and therefore result in significant costs to both healthcare systems and society. Surgical site infections (SSIs) are common following all surgical interventions, and within hand surgery the risk of SSI is at least 5%. SSI following hand trauma surgery results in significant costs to healthcare systems with estimations of over £450 per patient. The World Health Organization (WHO) have produced international guidelines to help prevent SSIs. However, it is unclear what variability exists in the adherence to these guidelines within hand trauma. The aim is to assess compliance to the WHO global guidelines in prevention of SSI in hand trauma.

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With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting.

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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.

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Surgeon and patient reluctance to participate are potential significant barriers to conducting placebo-controlled trials of orthopaedic surgery. Understanding the preferences of orthopaedic surgeons and patients regarding the design of randomized placebo-controlled trials (RCT-Ps) of knee procedures can help to identify what RCT-P features will lead to the greatest participation. This information could inform future trial designs and feasibility assessments.

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Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted.