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

In recent literature, the fragility index (FI) has been used to evaluate the robustness of statistically significant findings of dichotomous outcomes. This metric is defined as the minimum number of outcome events to flip study conclusions from significant to nonsignificant. Orthopaedics literature is frequently found to be fragile with a median FI of 2 in 150 RCTs across spine, hand, sports medicine, trauma and orthopaedic oncology studies. While many papers discuss limitations of FI, we aimed to further characterize it by introducing the Fragility Likelihood (FL), a new metric that allows us to consider the probability of the event to occur and to calculate the likelihood of this fragility to be reached. We systematically reviewed all randomized controlled trials in the Journal of Bone and Joint Surgery (Am) over 10 years. The FL was calculated with the following formula: A x B x C x 100% (A= FI; B = probability of the event in the group with the smallest number of events; C= probability of the non-event in the group with the highest number of events). A smaller FL demonstrates more robust results and conversely, a larger FL illustrates a higher likelihood of fragility being reached and more fragile the findings. The median FI for the statistically significant outcomes was 2 (Mean: 3.8; Range 0-23). The median FL for the statistically significant outcomes was 11% (Mean: 22%, Range: 2%-73%). This means that the probability of reaching non-significance is only 11% when considering the probability of the event to occur. When comparing studies with the same FI we found the FL to range from 3% to 43%. This illustrates the large differences in robustness between trials with equal FI when the likelihood of the event was taken into consideration. As orthopaedic studies are frequently reported as fragile, we found that by calculating the FL, studies may be more robust than previously assumed based off FI alone. By using the FL in conjunction with FI and p-values will provide additional insight into the robustness of the reported outcomes. Our results indicate that by calculating the FL, study conclusions are stronger than what the FI alone predicts. Although conducting RCTs in surgery can be challenging, we must endeavor to critically evaluate our results so we can answer important orthopaedic questions with certainty

The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject. A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing zoledronic acid with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures. Four RCTs (7320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumour types were combined (OR 0.86, 95% CI [0.74, 0.99], p = 0.04). Denosumab was not significantly favoured over ZA in endodermal origin (breast and prostate) (OR 0.85, 95% CI [0.68, 1.05], p = 0.13) and mesodermal origin tumours (solid tumours and MM) (OR 0.87, 95% CI [0.71, 1.06], p = 0.16). Denosumab significantly reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases. When pathological fractures were grouped by tumour origin (endodermal or mesodermal), there was no significant difference between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens

To determine in skeletally mature patients with a traumatic, first-time, patellar dislocation, the effect of early MPFL reconstruction versus rehabilitation on the rate of recurrent patellar dislocations and functional outcomes. Three online databases MEDLINE, EMBASE and PubMed were searched from database inception (1946, 1974, 1966 respectively), to August 20th, 2021, for literature addressing the management of patients sustaining acute first-time patellar dislocations. Data on redislocation rates, functional outcomes using the Kujala score, and complication rates were recorded. A meta-analysis was used to pool the mean postoperative kujala score as well as calculate the proportion of patients sustaining redislocation episodes using a random effects model. A risk of bias assessment was performed for all included studies using the MINORS and Detsky scores. Overall, there were a total of 22 studies and 1705 patients included in this review. The pooled mean redislocation rate in 18 studies comprising 1409 patients in the rehabilitation group was 31% (95% CI 25%-36%, I2 = 65%). Moreover, the pooled mean redislocation rate in five studies comprising 318 patients undergoing early MPFL reconstruction was 7% (95% CI 2%-17%, I2 = 70%). The pooled mean postoperative Kujala anterior knee pain score in three studies comprising 67 patients in the reconstructive group was 91 (95% CI 84-97, I2 = 86%), compared to a score of 81 (95% CI 78-85, I2 = 78%) in 7 studies comprising 332 patients in the rehabilitation group. The reoperation rate was 9.0% in 936 patients in the rehabilitation group and 2.2% in 322 patients in the reconstruction group. Management of acute first-time patellar dislocations with MPFL reconstruction resulted in a lower rate of redislocation and a higher Kujala score, as well as noninferiority with respect to complication rates compared to nonoperative treatment. The paucity of high-level evidence warrants further investigation in this topic in the form of well-designed and high-powered RCTs to determine the optimal management option in these patients

The aim was to analyze whether non-steroidal anti-inflammatory drugs (NSAIDs) have an adverse effect on bone healing by evaluating all available human randomized controlled trials (RCTs) on this subject. A systematic search of electronic databases (PubMed, MEDLINE, and Cross-References) was performed to identify RCTs comparing the occurrence of nonunion in patients who received NSAIDs to the control group. Risk of bias of the studies was assessed. Nonunion was the main outcome evaluated, however, regression analysis was used to estimate the relative risk comparing duration and type of NSAIDs. Six RCTs (609 patients) were included. The risk of nonunion was higher in the patients given NSAIDs after the fracture (P-value= 0.0009, relative risk [RR] = 2.9, 95% confidence interval [CI] = 1.6 to 6.3). However, once the studies have been categorized to the duration of NSAIDs, those who received short period of NSAIDs (4 weeks) (P-value = 0.0002, RR = 4.1, CI = 2.1 to 8). Also, indomethacin agent has associated with high nonunion (P-value = 0.0001, RR = 3.9, CI = 2.3 to 13.9) compared to other NSAIDs which did not show a nonunion risk (P-value = 0.24, RR = 2.3, CI = 0.6 to 8.9). Using NSAIDs for long period (> 4 weeks) after fracture is significantly associated with nonunion especially with indomethacin agent. However, short period of NSAIDs (< 2 weeks) did not show the adverse effects of nonunion. Overall, further studies are required to support our conclusion

Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer

Introduction. Treatment of non-union in open tibial fractures Gustilo-Anderson(GA)-3A/3B fractures remains a challenging problem. Most of these can be dealt using treatment methods that requires excision of the non-union followed by bone grafting, masquelet technique, or acute shortening. Circular fixators with closed distraction or bone transport also remains a useful option. However, sometimes due to patient specific factors these cannot be used. Recently antibiotic loaded bone substitutes have been increasingly used for repairing infected non-unions. They provide local antibiotic delivery, fill dead space, and act as a bone conductive implant, which is resorted at the end of a few months. We aimed to assess the outcome of percutaneous injection of bone substitute while treating non-union of complex open tibial fractures. Materials & Methods. Three cases of clinical and radiological stiff tibial non-union requiring further intervention were identified from our major trauma open fracture database. Two GA-3B cases, treated with a circular frame developed fracture-related-infection(FRI) manifesting as local cellulitis, loosened infected wires/pins with raised blood-markers, and one case of GA-3A treated with an intramedullary nail. At the time of removal of metalwork/frame, informed consent was obtained and Cerament-G. TM. (bone-substitute with gentamicin) was percutaneously injected through a small cortical window using a bone biopsy(Jamshedi needle). All patients were allowed to weight bear as tolerated in a well-fitting air-cast boot and using crutches. They were followed up at 6 weekly intervals with clinical assessment of their symptoms and radiographs. Fracture union was assessed using serial radiographs with healing defined as filling of fracture gap, bridging callus and clinical assessment including return to full painless weight bearing. Results. Follow-up at 6 months showed all fractures had healed with no defect or gaps with evidence of new trabecular bone and significant resorption of Cerament-G. TM. at final follow-up. There was no evidence of residual infection with restoration of normal limb function. Fractures with no internal fixation showed a mild deformity that had developed during the course of the healing, presumed due to mild collapse in the absence of fixation. These were less than 10 degrees in sagittal and coronal planes and were clinically felt to be insignificant by the patients. Conclusions. Cerament-G's unique combination of high dose antibiotics and hydroxy apatite matrix provided by calcium sulphate might help provide an osteoconductive environment to allow these stiff non-unions to heal. The matrix appears to provide a scaffold-like structure that allows new bone in-growth with local release of antibiotics helping reduce deep-seated infections. The final deformation at fracture site underlines the need for fixation- and it is very unlikely that this technique will work in mobile nonunions. Whilst similar fractures may heal without the use of bone substitute injections, the speed of healing in presence of significant fracture gap suggests the use of these bone substitutes did help in our cases. Further studies with a larger cohort, including RCTs, to evaluate the effectiveness of this technique compared to other methods are needed

Background. Effectiveness of computer-assisted joint replacement (CA-TJR) compared to conventional TJR has been evaluated by a large body of literature. Systematic reviews provide a powerful, widely accepted, evidence-based approach to synthesize the evidence and derive conclusions, yet the strength of these conclusions is dependent on the quality of the review. Multiple systematic reviews compared CA-TJR and conventional TJR with conflicting results. We aimed to assess the quality of these reviews. Methods. We searched MEDLINE, EMBASE, the Cochrane, and Epistemonikos to identify SRs published through May 2017. Full-text articles that met inclusion criteria were retrieved and assessed independently by two reviewers. Evidence was qualitatively synthesized and summarized. Outcome measures were categorized into functional, radiological, and patient safety related. The corrected covered area (CCA) was calculated to assess the degree of overlap between SRs in analyzing the same primary studies. The AMSTAR 2, a valid and reliable tool, was applied to rate the confidence in the results of the SRs (Shea et al., 2017). AMSTAR-2 has 16 domains, of which 7 are critical (e.g., justification for excluding individual studies) and 9 are non-critical (e.g., not reporting conflict of interest for individual studies). Reviews are rated as high (no critical or non-critical flaws), moderate (only non-critical flaws), low (1 critical flaw) and critically low (more than one critical flaw). Disagreement between the 2 reviewers was resolved by discussion with the senior author to achieve consensus. We reported the quality ratings of these studies and the frequency of critical and non-critical flaws. Results. Of 384 citations originally identified, 37 systematic reviews were included. Meta-analyses that addressed TKA showed discrepancy on functional (e.g. KSS), radiological (mechanical axis malalignment), and patient safety (e.g. adverse events) outcomes. Meta-analyses that addressed THA showed more consistent results. Moderate overlap was observed among TKA SRs (CCA=7%) and very high overlap among THA SRs (CCA=26%). Based on the AMSTAR 2 tool, 35 studies were rated critically low and two studies were rated low. Low rating was due to failure in: developing a review protocol (94.6%); using a comprehensive search strategy (56.8%), providing a list of excluded studies (89%); accounting for risk of bias in the primary RCTs (44%), accounting for the risk of bias of the primary studies when discussing the results (70%), performing appropriate statistical methods (53% for RCTs and 88% for non-RCTs), and adequately investigating publication bias (53%). Conclusions. Given the very low confidence in the results of the SRs comparing CA to conventional total joint arthroplasty, clinicians should interpret the results of these SRs with caution. High methodological quality SRs are needed to inform evidence-based clinical practice

A commonly misunderstood principle in medical literature is statistical significance. Often, statistically non-significant or negative results are thought to be evidence for equivalence; mistakenly validating treatment modalities and putting patients at risk. This study examines the prevalence of misinterpretation of negative results of superiority trials in orthopaedic literature and outlines the need for a non-inferiority or equivalence research design. Four orthopaedic journals – Journal of Paediatric Orthopaedics A, Journal of Bone and Joint Surgery American Volume, Journal of Arthroplasty and Journal of Shoulder and Elbow Surgery – were hand searched to identify all randomised control trials (RCTs) published within the time periods 2002–2003, 2007–2008 and 2012–2013. The identified RCTs were read and classified by study methodology, results obtained, and interpretation of results. A total of 237 RCTs were identified. When analysing the primary outcomes, 117 (49.4%) studies yielded negative results and 120 (50.8%) yielded positive results. Out of the 237 articles, 231 (97.5%) used superiority methodology and 6 (2.5%) used non-inferiority or equivalence methodology. Of the 231 studies that used superiority methodology, 115 (49.8%) obtained negative results; and 45 (39.1%) of those misinterpreted the negative results for equivalence. While no statistical differences were seen, there was an upward trend in utilising non-inferiority and equivalence methodologies over time. Given the frequency of misinterpreted negative results, there is an evident need for a more appropriate research methodology that shows equivalence of treatment methods. A non-inferiority or equivalence study design can address orthopaedic clinical dilemmas more suitably when trying to show one treatment is no worse or is equal to another treatment. Regarding orthopaedic treatment modalities as equivalent when studies show negative statistical results can be detrimental to patients and their clinical outcomes. A non-inferiority methodology can be used to accurately depict no difference between treatment methods rather than attempting to show one treatment method as superior

Background. To conduct a systematic review and network meta-analysis of RCTs with the aims of comparing relevant clinical outcomes (i.e. VAS, WOMAC total and sub-score score, Lequesne Algofunctional index, joint space width change and adverse events) between diacerein, glucosamine and placebo. Methods. Medline and Scopus databases were searched from inception to August 29th, 2014, using PubMed and Scopus search engines and included RCTs or quasi-experimental designs comparing clinical outcomes between treatments. Data were extracted from original studies. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. Results. Thirty-one of 505 identified studies were eligible. Compared to placebo, glucosamine showed significant improvement with unstandardized mean differences (UMD) in total Western Ontario and McMaster Universities Osteoarthritis index (WOMAC), pain WOMAC, function WOMAC, and Lequesne score of −2.49 (95% confidence interval [CI], −4.14, −0.83), −0.75 (95% CI, −1.18, −0.32), −4.78 (95% CI, −5.96, −3.59) and −1.03 (95% CI, −1.34, −0.72), respectively. Diacerein clinically improves visual analog scores, function WOMAC, and stiffness WOMAC with UMD values of −2.23 (95% CI, −2.82, −1.64), −6.64 (95% CI, −10.50, −2.78) and −0.68 (95% CI, −1.20, −0.16) when compared to placebo. Conclusions. The network meta-analysis suggests that diacerein and glucosamine are equally efficacious for symptom relief in knee OA, but that the former has more side effects

Persistent post-surgical pain affects 10%-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent postsurgical pain and physical impairment. We searched Medline, PsycINFO, CINAHL, and the Cochrane Central Registry of Controlled Trials to identify relevant RCTs, in any language, from inception of each database to September 1, 2016. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. We pooled treatment effects of perioperative psychotherapy on similar outcomes across eligible trials, focusing on intention-to-treat analysis. We used random effects models to perform all meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Our search found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) −1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) −1.56 to −0.55 cm, risk difference (RD) for achieving no more than mild pain (3 cm or less) 14%, 95% CI 8–21%] and physical impairment [WMD −9.87% on the 0–100% Oswestry Disability Index, 95% CI −13.42 to −6.32%, RD for achieving no more than mild disability (20% or less) 21%, 95% CI 13–29%]. Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. High quality evidence shows no significant effects of perioperative education or psychological support on persistent post-surgical pain or physical impairment compared with usual care. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome

Ten RCTs published between 2000 and 2013 support treating distal radius buckle fractures and other low-risk distal radius fractures with a removable splint and with no orthopaedic follow-up. Application of this evidence has been shown to be variable and suboptimal resulting in unnecessary costs to a strained healthcare system. The Canadian evidence on this topic has been generated by subspecialist physicians working in paediatric hospitals. It is unclear what factors affect the dissemination of this information. We investigated the association of hospital type and physician type with the application of best-evidence treatment for low-risk distal radius fractures in children with the goal of improving our understanding of evidence diffusion in Ontario for this common injury. We performed a retrospective population-based cohort study using linked health care administrative data. We identified all children aged 2–14 treated in Ontario emergency departments from 2003–2015 with distal radius fractures with no reduction and no operation within a six week period. We excluded refractures and children with comorbidities. We evaluated the followup received – orthopaedic, general practitioner, or none. We examined the data for trends over time. Multivariable log binomial regression was used to quantify associations between hospital and physician type and best-evidence treatment. We adjusted for patient-related variables including age, sex, rural or urban location, and socioeconomic status. 70,801 fractures were analyzed. Best-evidence treatment was more likely to occur in a small (RR 1.86, 95%CI 1.72–2.01), paediatric (RR 1.16, 95%CI 1.07–1.26), or community (RR 1.13, 95%CI 1.06–1.20) hospital compared with treatment in a teaching hospital. Best-evidence treatment was more likely if initial management was by a paediatrician with additional emergency medicine training (RR 1.73, 95%CI 1.56–1.92) or paediatrician (RR 1.22, 95%CI 1.11–1.34). Paediatric and teaching hospitals have improved their use of best-evidence over time while other hospital types have stagnated or deteriorated. Paediatricians, paediatricians with additional emergency medicine training, and emergency medicine residency trained physicians have improved their use of best-evidence over time, while other physician types have stagnated or deteriorated. Overall, only 20% of patients received best-evidence treatment and 70% had orthopaedic follow-up. Significant over-utilization of resources for low-risk distal radius fractures continues decades after the first randomized trials showed it to be unnecessary. Physician type and hospital rurality are most strongly associated with best-evidence treatment. Physician types involved in generating, presenting, and publishing best-evidence for this fracture type are successfully implementing it, while others have failed to change their practices. Rural hospitals are excellent resource stewards by necessity, but are deteriorating over time. Our results strongly indicate the need for targeted implementation strategies to explicitly apply clinical evidence in clinical practice Canada-wide, with the goal of providing more cost-effective care for common children's fractures

Purpose. Infections in orthopaedic surgery are costly, debilitating complications. The search for new treatments and prevention strategies has led to the use of antibiotic-filled calcium sulfate (CaS) as a bone void filler that is both safe and effective. The purpose of this study was to examine the available data on the efficacy of this technology. Methods. A literature search was performed for studies that evaluated the use of antibiotic-loaded CaS cement in orthopaedics published between inception of the databases to 2017. Selected studies included randomized controlled trials (RCTs) and observational studies published in the English language that met the following criteria: 1) patients underwent an orthopaedic procedure; 2) CaS cement with an antibiotic was used; and 3) at least one of our outcomes were mentioned. Outcomes included resolution of infection, complications related to treatment, subsequent surgeries, overall infection rate, fracture union rate, clinical outcomes, and wound complications. A total of 17 studies were included. Results. Ten studies examined the use of antibiotic-eluting CaS cement with surgical debridement to treat osteomyelitis and reported resolution rates ranging from 80–100%. Two studies examined CaS for prophylaxis of infection after open fracture, with subsequent infection rates ranging from 0–22%. Two studies examined infected non-unions with CaS used as an adjunct to surgery with an 87.5% infection clearance rate. Finally, three studies examined the use of local antibiotic release from CaS in the repair of infected TKAs or THAs, with success rates ranging from 52–93.3%. Conclusion. Initial results support the use of CaS with surgical debridement for osteomyelitis and infected non-unions. Results are mixed for CaS use in the prophylaxis of infection after open fractures and for PJIs, thereby necessitating further research. Overall the studies were small, retrospective, and lacked controls. Further research should focus on RCTs to minimize bias and investigate for non-inferiority. For any figures or tables, please contact authors directly

Three-dimensional (3D) printing has become more frequently used in surgical specialties in recent years. Orthopaedic surgery is particularly well-suited to 3D printing applications, and thus has seen a variety of uses for this technology. These uses include pre-operative planning, patient-specific instrumentation (PSI), and patient-specific implant production. As with any new technology, it is important to assess the clinical impact, if any, of three-dimensional printing. The purpose of this review was to answer the following questions: . What are the current clinical uses of 3D printing in orthopaedic surgery?. Does the use of 3D printing have an effect on peri-operative outcomes?. Four electronic databases (Embase, MEDLINE, PubMed, Web of Science) were searched for Articles discussing clinical applications of 3D printing in orthopaedics up to November 13, 2018. Titles, abstracts, and full texts were screened in duplicate and data was abstracted. Descriptive analysis was performed for all studies. A meta-analysis was performed among eligible studies to compare estimated blood loss (EBL), operative time, and fluoroscopy use between 3D printing cases and controls. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria for non-randomized studies and the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs). This review was prospectively registered on PROSPERO (Registration ID: CRD42018099144). One-hundred and eight studies were included, published between 2012 and 2018. A total of 2328 patients were included in these studies, and 1558 patients were treated using 3D printing technology. The mean age of patients, where reported, was 47 years old (range 3 to 90). Three-dimensional printing was most commonly reported in trauma (N = 41) and oncology (N = 22). Pre-operative planning was the most common use of 3D printing (N = 63), followed by final implants (N = 32) and PSI (N = 22). Titanium was the most commonly used 3D printing material (16 studies, 27.1%). A wide range of costs were reported for 3D printing applications, ranging from “less than $10” to $20,000. The mean MINORS score for non-randomized studies was 8.3/16 for non-comparative studies (N = 78), and 17.7/24 for non-randomized comparative studies (N = 19). Among RCTs, the most commonly identified sources of bias were for performance and detection biases. Three-dimensional printing resulted in a statistically significant decrease in mean operative time (−15.6 mins, p < .00001), mean EBL (−35.9 mL, p<.00001), and mean fluoroscopy shots (−3.5 shots, p < .00001) in 3D printing patients compared to controls. The uses of 3D printing in orthopaedic surgery are growing rapidly, with its use being most common in trauma and oncology. Pre-operative planning is the most common use of 3D printing in orthopaedics. The use of 3D printing significantly reduces EBL, operative time, and fluoroscopy use compared to controls. Future research is needed to confirm and clarify the magnitude of these effects

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

Acute metatarsal fractures are a common extremity injury. While surgery may be recommended to reduce the risk of nonunion or symptomatic malunion, most fractures are treated with nonoperative management. However, there is significant variability between practitioners with no consensus among clinicians on the most effective nonoperative protocol, despite how common the form of treatment. This systematic review identified published conservative treatment modalities for acute metatarsal fractures and compares their non-union rate, chronic pain, and length of recovery, with the objective of identifying a best-practices algorithm. Searches of CINAHL, EMBASE, MEDLINE, and CENTRAL identified clinical studies, level IV or greater in LOE, addressing non-operative management strategies for metatarsal fractures. Two reviewers independently screened the titles, abstracts, and full texts, extracting data from eligible studies. Reported outcome measures and complications were descriptively analyzed. Studies were excluded if a rehabilitation program outlining length of immobilization, weight-bearing and/or strengthening approaches was not reported. A total of 12 studies (8 RCTs and 4 PCs), from the 2411 studies that were eligible for title screening, satisfied inclusion criteria. They comprised a total of 610 patients with acute metatarsal fractures, with a mean age of 40.2 years (range, 15 – 82). There were 6 studies that investigated avulsion fractures, 2 studies on true Jones fractures, and 4 studies with mixed fracture types. Studies assessed a variety of treatment modalities including: WB and NWB casts, elasticated support bandages, hard-sole shoes, plaster slippers, metatarsal shoe casts, and air cast boots. Most studies investigated the outcomes of NWB casts and elasticated support bandages. The NWB short leg cast had no reported non-unions, delayed-unions, or refractures for avulsion fractures. In true Jones fractures, there was an average non-union rate of 23.6% (range, 5.6 – 27.8%), delayed-union rate of 11.8% (range, 5.6 – 18.8%), and refracture rate of 3% (range, 0 – 5.6%). Overall, the average AOFAS score was 87.2 (range, 84 – 91.7) and the average VAS score was 83.7 (range, 75 – 93). The elasticated support bandage had an average non-union rate of 3.4% (range, 0 – 12%), and delayed-union rate of 3.8% for acute avulsion fractures, with no reported refractures. No included study arm investigated outcomes of elasticated support bandages for the true Jones fracture. The average AOFAS score for elasticated support bandages was 93.5 (range, 90 – 100). The average VAS score was 88.9 (range, 90 – 100). Most acute metatarsal fractures heal well, with good-to-excellent functional outcomes and moderate-to-high patient satisfaction. Conservative strategies for avulsion fractures are highly successful and based on this data the authors recommend patients undergo a schedule that involves 3 – 4 weeks in an elasticated support bandage, short leg cast, or equivalent, and WB thereafter as tolerated, with return-to-activity after clinical union. Despite poorer conservative outcomes for true Jones fractures, patients should undergo 8 weeks in a NWB short leg cast, followed by a walking cast or hard-sole shoe for an additional 4 – 6 weeks, or until clinical union. However, surgical consultation is recommended

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.

Bearing surfaces in Total Hip Arthroplasty (THA) may affect implant longevity and hence patient outcomes. This randomised clinical trial (RCT) determined how ceramic-on-ceramic bearing (CERAMIC) THA affected joint-specific pain, function and stiffness, and prosthesis fixation/longevity over 10 postoperative years compared with ceramic-on-highly-crosslinked-polyethylene bearing (POLYETHYLENE) THA. This is a follow-up to previously reported five year outcomes. Subjects aged less than 61 years were randomised to CERAMIC [n=48] or POLYETHYLENE [n=44] THA. Subjects were assessed using the Western Ontario McMaster Osteoarthritis Index (WOMAC) and the RAND 12-Item Health Survey (RAND-12) preoperatively, and at one, five and 10 years postoperatively. Plain radiographs were evaluated at 10 years for fixation and medical records were reviewed for revisions. Of 92 subjects, six (7%) died within 10 years; 68 (79%) survivors provided radiographic and/or clinical follow-up at 10 years postoperatively. Improvements seen at five years in both the WOMAC and RAND-12 were retained at 10 years with no group differences (p>0.48). There were no failures/loss of fixation related to bearing surfaces/wear in either group. Over 10 years, three subjects in the POLYETHYLENE group had revisions that were related to recurrent dislocation; two revisions were performed within two years of surgery and one further subject underwent revision at 7 years postoperatively. This is one of the first RCTs to examine 10 year outcomes between ceramic-on-ceramic and ceramic-on-highly-crosslinked-polyethylene bearing THA. Both bearing surfaces performed well out to 10 years in subjects who were less than 61 years at time of surgery

Wear of the tibial polyethylene liner of total knee arthroplasty (TKA) is complex and multifactorial. The issues involved include those of implant design and locking mechanism, surgical-technical variability, and patient weight and activity level. However, tibial polyethylene fabrication, including bar stock, amount of irradiation, quenching of free radicals, and sterilization may also be factors in the long-term survival of TKA. Highly crosslinked polyethylene is now widely used in total hip arthroplasty, but its value and use in TKA is a subject of great controversy. In making a decision to use these products, the surgeon should consider multiple sources of evidence: in-vitro wear testing; clinical cohort studies; randomised controlled trials; registry survival data; and retrieval analyses. The two questions to be asked are: is there a value or benefit in the use of these new polyethylenes, and what are the risks involved with the use of these products?. Laboratory testing, generally to 5 million cycles, has shown a significant decrease in tibial polyethylene wear of several products, with both cruciate-retaining and substituting designs, and under adverse conditions. Retrospective cohort studies and RCTs comparing conventional and highly crosslinked polyethylene have shown little difference between the two products at mean follow-up times of 5 years. One registry study showed no difference in the rate of revision at short-term follow-up, but the Australian Joint Replacement Registry in 2014 did report a decreased rate of revision for loosening and osteolysis in “young patients” with one particular tibial polyethylene. The risks of the use of highly crosslinked polyethylene include fracture (the tibial liner, PS post, and patella pegs), and particle size-reactivity. However, these risks appear to be quite low. Retrieval data shows lower damage scores with certain polyethylenes, and variable changes in the oxidation score. At present, the data does not support the widespread or routine use of highly crosslinked or antioxidant polyethylene in TKA. However, consideration should be given for use of certain products in young and active patients. Longer-term follow-up will ultimately determine the role of highly crosslinked polyethylene in TKA

Aims

Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence.