Abstract. Objectives. To compare the effectiveness of phonophoresis (PH) and conventional therapeutic ultrasound (US) on the functional and pain outcomes of patients with knee osteoarthritis. Methods. We conducted an electronic search through PubMed, Cochrane Central Register of Clinical Trials (CENTRAL), Web of Science (WOS), and Scopus databases. We screened the retrieved articles to include only English full-text randomized controlled trials that examined the effect of phonophoresis versus conventional therapeutic ultrasound on patients with knee osteoarthritis. Two reviewers screened, extracted the data, and independently assessed the quality of the included articles. Results. A total of five randomized controlled trials met our inclusion criteria out of 267 studies screened. Our results showed no statistically significant differences between the PH and US groups (1), (2), (3),(4), and (5). The PH group demonstrated more significant effects than the UT group in reducing VAS pain scores (P=0.009) and improving WOMAC scores, although this did not reach the level of significance (P=0.143) (5). In the long term, PH therapy was found to be superior to US in improving painless walking duration and distance VAS scores (p=0.034, 0.017) respectively, as well as walking and resting walking VAS scores (p=0.03, 0.007) respectively, which were found to be permanent (3). Conclusions. Both therapies improve pain and function. However, we suggest conducting more high-quality trials with larger sample sizes and do not recommend the use of these therapies in clinical practice due to limitations in gender selection and high risk of bias. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Intra-articular injection is a common way to deliver biologics to joints, but their effectiveness is limited by rapid clearance from the joint space. This barrier can be overcome by genetically modifying cells within the joint such that they produce anti-arthritic gene products endogenously, thereby achieving sustained, therapeutic, intra-articular concentrations of the transgene products without re-dosing. A variety of non-viral and viral vectors have been subjected to preclinical testing to evaluate their suitability for delivering genes to joints. The first transfer of a gene to a human joint used an ex vivo protocol involving retrovirally transduced, autologous, synovial fibroblasts. Recent advances in vector technology allow in vivo delivery using adeno-associated virus (AAV). We have developed an AAV vector encoding the interleukin-1 receptor antagonist (AAV.IL-1Ra) for injection into joints with osteoarthritis (OA). It showed efficacy and safety in equine and rat models of OA, leading to a recently-completed, investigator-initiated, Phase I, dose-escalation clinical trial in 9 subjects with mid-stage OA of the knee (ClinicalTrials.gov Identifier: NCT02790723). Three cohorts of three subjects with mild to moderate OA in the index knee were injected intra-articularly under ultrasound guidance with a low (10e11 viral genomes) medium (10e12 viral genomes) or high (10e13 viral genomes) dose of AAV.IL-1Ra and followed for one year. The data confirm safety, with evidence of sustained intra-articular expression of IL-1Ra and a clinical response in certain subjects. Funding for a subsequent Phase Ib trial involving 50 subjects (ClinicalTrials.gov Identifier: NCT05835895), expected to start later this year, has been acquired. Progress in this area has stimulated commercial activity and there are now at least seven different companies developing gene therapies for OA and a number of clinical trials are in progress.

Acknowledgement: Clinical trial funded by US Department of Defense Clinical Trial Award W81XWH-16-1-0540.

Many orthopaedic procedures require implants to be trialled before definitive implantation. Where this is required, the trials are provided in a set with the instrumentation. The most common scenario this is seen in during elective joint replacements. In Scotland (2007) the Scottish Executive (. http://www.sehd.scot.nhs.uk/cmo/CMO(2006)13.pdf. ) recommended and implemented individually packed orthopaedic implants for all orthopaedic sets. The premise for this was to reduce the risk of CJD contamination and fatigue of implants due to constant reprocessing from corrosion. During many trauma procedures determining the correct length of plate or size of implant can be challenging. Trials of trauma implants is no longer common place. Many implants are stored in closed and sealed boxes, preventing the surgeon looking at the implant prior to opening and contaminating the device. As a result many implants are incorrectly opened and either need reprocessed or destroyed due to infection control policy, thus implicating a cost to the NHS. With even the simplest implants costing several hundreds of pounds, this cost is a very significant waste in resources that could be deployed else where. My project was to develop a method to produce in department accurate, cheap and disposable trials for implants often used in trauma, where the original manufacturer do not offer the option of a trial off the shelf. The process had to not involve contaminating or destroying the original implant in the production of a trial. Several implants which are commonly used within Glasgow Royal Infirmary and do not have trials were identified. These implants were then CT scanned within their sealed and sterile packaging without contamination. Digital 3D surface renders of the models were created using free open source software (OsiriX, MeshLab, NetFabb). These models were then processed in to a suitable format for 3D printing using laser sintering via a cloud 3D printing bureau (. Shapeways.com. ). The implants were produced in polyamide PA220 material or in 316L stainless steel. These materials could be serialized using gamma irradiation or ethylene oxide gas. The steel models were suitable for autoclaving in the local CSSU. The implants produced were accurate facsimiles of the original implant with dimensions within 0.7mm. The implants were cost effective, an example being a rim mesh was reproduced in polyamide PA220 plastic for £3.50 and in 316L stainless steel for £15. The models were produced within 10 days of scanning. The stainless steel trials were durable and suitable for reprocessing and resterilisation. The production of durable, low cost and functional implant trials all completed in department was successful. The cost of production of each implant is so low that it would be offset if just one incorrect implant was opened during a single procedure. With some of the implants tested, the trials would have paid for themselves 100 times. This is a simple and cost saving technique that would help reduce department funding and aid patient care

Abstract

Our objective was to conduct a systematic review and meta-analysis, comparing differences in clinical outcomes between either autologous or synthetic bone grafts in the operative management of tibial plateau fractures: a traumatic pattern of injury, associated with poor long-term functional prognosis.

A structured search of MEDLINE, EMBASE, The Bone & Joint and CENTRAL databases from inception until 07/28/2021 was performed. Randomised, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture non-union or chondral defects were excluded. Outcome data was assessed using the Risk of Bias 2 (ROB2) framework and synthesised in random-effect meta-analysis. Preferred Reported Items for Systematic Review and Meta-Analysis guidance was followed throughout.

Six comparable studies involving 352 patients were identified from 3,078 records. Following ROB2 assessment, five studies (337 patients) were eligible for meta-analysis. Within these studies, more complex tibia plateau fracture patterns (Schatzker IV-VI) were predominant. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference −0.45mm, p=0.25, 95% confidence interval (95%CI): −1.21-0.31mm, I²=0%) and long-term (>6 months, standard mean difference −0.56, p=0.09, 95%CI: −1.20-0.08, I²=73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, defect site pain, occurrence of surgical site infections, secondary surgery, perioperative blood loss, and duration of surgery. Blood loss was lower (90.08ml, p<0.001, 95%CI: 41.49-138.67ml, I²=0%) and surgery was shorter (16.17minutes, p=0.04, 95%CI: 0.39-31.94minutes, I²=63%) in synthetic treatment groups. All other secondary measures were statistically comparable.

Our findings supersede previous literature, demonstrating that synthetic bone grafts are non-inferior to autologous bone grafts, despite their perceived disadvantages (e.g. being biologically inert). In conclusion, surgeons should consider synthetic bone grafts when optimising peri-operative patient morbidity, particularly in complex tibial plateau fractures, where this work is most applicable.

We have undertaken a series of clinical trials over the last 20 years to look at different bearing surface combinations in young adults. We continue to follow these patients well beyond the planned duration of the trials and new information is constantly becoming available. The first trial compared ceramic-on-ceramic with ceramic-on-standard-polyethylene. These patients have now been followed for 20 years with significant wear in the polyethylene group but virtually identical revision rates. The second trial ceramic-on-ceramic, cobalt-chrome-on-standard-polyethylene and cobalt-chrome-on-cross-linked-polyethylene. In this group the ceramic-on-ceramic patients have the lowest revision rate; the ceramic-on-polyethylene group demonstrates a lower wear rate than cobalt-chrome-on-polyethylene. The third trial looks at cobalt-chrome versus zirconium on either cross-linked polyethylene or conventional polyethylene. At 10 years there remains no evidence of improved performance from the zirconium surface as compared to cobalt-chrome. The cross-linked polyethylene group is clearly outperforming the conventional polyethylene in terms of wear rate but at 10 years the revision rates remain the same in all groups. Cross liked polyethylene appears to be the major determining factor in prosthetic longevity and appears to be more important than the counter face material.

Mesenchymal Stromal Cells (MSC) have been proposed as a potential therapy for a broad range of diseases including those affecting the musculoskeletal system. MSCs have received market authorization for treatment of graft versus host disease and fistulizing Crohn's disease. In addition, there are clinical trials underway for diseases affecting all organ systems. GMP manufactured cells are required for these clinical trials and suitable facilities with regulatory approval are thus crucial for the translational process. In this presentation I will review the process whereby such a facility has been constructed at NUI Galway and discuss challenges in operations and sustainability. Researchers at REMEDI and spin out company Orbsen Therapeutics are currently involved in 7 clinical trials using MSCs, 4 of which are EU wide consortia funded by the EU Commission. The presentation will also discuss issues such as source of MSCs, cell sorting, use of bioreactors and xeno-free processes.

Lower limb fractures are commonly treated with cast immobilization, and as a main consequence of strict immobilization this typically leads to loss in muscle mass, decrease of bone density and decline in functional abilities. Body-worn sensors are increasingly used to assess outcome in clinical trials by providing objective mobility parameters in a real-world environment. The aim of this study is to investigate the usability aspects and potential changes in mobility parameters in partial-immobilization patients in real-world conditions. Six healthy young males (age 22.2 ± 1.2 years; weight 76.5 ± 6.7 kg, height 185.8 ± 6.1 cm. Mean ± standard deviation) wore a leg cylinder cast with walker boot to immobilize their dominant leg for two consecutive weeks. Subjects were asked to continuously wear a tri-axial accelerometer on the waist (actibelt) during waking hours for 6 weeks including 2 weeks before, during and after cast immobilisation. The total amount of days of continuous recording was 339 days with a total wearing time of 120 days. Software packages which allow to detect steps and to estimate real-world walking speed were used to analyse the accelerometry data. It was suspected that knee immobilization would affect strongly the wave form of the signal with an impact on the accuracy of the speed algorithm, whereas the step detection should be more robust. This effect was confirmed in a preliminary study performed to quantify the accuracy under immobilization conditions. On the other hand, step numbers are known to be sensitive to fluctuations in wearing time which was not uniform throughout the entire study. We concluded that in this setting step frequency is the most reliable parameter. Step frequency showed a systematic decrease in the values during the immobilization period which recovered to pre-immobilisation values after cast removal. This confirms the usability of accelerometry and sensitivity of its mobility parameters for clinical outcome assessment.

Background

Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7–23% of patients experience chronic post-surgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis.

Background

The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This abstract reports results of the within-trial economic evaluations.

Abstract. BACKGROUND. The effectiveness of anti-embolic graduated compression stockings (GCSs) has recently been questioned. The aim of this study is to systematically review all the relevant randomised controlled trials published to date. PATIENTS AND METHODS. We systematically reviewed all the randomised controlled trials comparing anti-embolism stockings with no stockings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL, Cochrane Musculoskeletal Injuries Group specialized register and the reference lists of articles as well as hand search results. Trials were independently assessed and data for the main outcome measures; deep vein thrombosis (DVT), pulmonary embolism and skin ulceration, were extracted by two reviewers. RESULTS. A total of 26 relevant RCTs involving 8279 participants were systematically reviewed. Theoccurrence of deep vein thrombosis was 306/4159(7.3%) with the stocking to 492/4120(11.9%) without the stockings (RR 0.49, 95% CI 0.39–0.62). The occurrence of pulmonary embolism was also reduced from 1.2% go 0.7% (95% 0.33–0.92). This initial finding was unsound due to the potential underreporting of negative studies and the subsequent changes to clinical practice. For the three large contemporary studies involving 5171 participants, these failed to show any statistically significant reduction in thrombosis, with DVT confirmed in 158(6.1%) participants in those allocated to stocking, as opposed to 171(6.6%) in the control group. CONCLUSION. The current recommendations regarding the use of GCSs need to be reconsidered, as their effectiveness at reducing the occurrence of post-operative DVT is minimal at best, based on the current evidence and clinical practices

Introduction and Objective. The effectiveness of anti-embolic graduated compression stockings (GCSs) has recently been questioned. The aim of this study is to systematically review all the relevant randomised controlled trials published to date. Materials and Methods. We systematically reviewed all the randomised controlled trials comparing anti-embolism stockings with no stockings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL, Cochrane Musculoskeletal Injuries Group specialized register and the reference lists of articles as well as hand search results. Trials were independently assessed and data for the main outcome measures; deep vein thrombosis (DVT), pulmonary embolism and skin ulceration, were extracted by two reviewers. Results. A total of 26 relevant RCTs involving 8279 participants were systematically reviewed. The occurrence of deep vein thrombosis was 306/4159 (7.3%) with the stocking to 492/4120 (11.9%) without the stockings (RR 0.49, 95% CI 0.39–0.62). The occurrence of pulmonary embolism was also reduced from 1.2% to 0.7% (95% 0.33–0.92). This initial finding was unsound due to the potential underreporting of negative studies and the subsequent changes to clinical practice. For the three large contemporary studies involving 5171 participants, these failed to show any statistically significant reduction in thrombosis, with DVT confirmed in 158 (6.1%) participants in those allocated to stocking, as opposed to 171 (6.6%) in the control group. Conclusions. The current recommendations regarding the use of thrombo-embolic stockings need to be reconsidered, as their effectiveness at reducing the occurrence of post-operative deep vein thrombosis is minimal at best, based on the current evidence and clinical practices

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared. 9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies. This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context

The aim of this study was to perform a systematic review of the literature on Gustilo-Anderson (GA) type IIIB open tibial shaft (AO-42) injuries to determine the consistency of reporting in the literature. A search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials was performed to identify relevant studies published from January 2000 to January 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The study was registered using the PROSPERO International prospective register of systematic reviews. Patient/injury demographics, management and outcome reporting were recorded. There were 32 studies that met the inclusion criteria with a total of 1,947 patients (70.3% male, 29.7% female). There were 6 studies (18.8%) studies that reported on comorbidities and smoking, with mechanism of injury reported in 22 (68.8%). No studies reported on all operative criteria included, with only three studies (9.4%) reporting for time to antibiotics, 14 studies (43.8%) for time from injury to debridement and nine studies (28.1%) for time to definitive fixation. All studies reported on the rate of deep infection, with a high proportion documenting union rate (26/32, 81.3%). However, only two studies reported on mortality or on other post-operative complications (2/32, 6.3%). Only 12 studies (37.5%) provided any patient reported outcomes. This study has demonstrated a deficiency and a lack of standardized variable and outcome reporting in the orthopaedic literature for Gustilo-Anderson type IIIB open tibial shaft fractures. We propose a future international collaborative Delphi process is needed to standardize

Intraoperative fractures although rare are one of the complications known to occur while performing a total hip arthroplasty (THA). However, due to lower incidence rates there is currently a gap in this area of literature that systematically reviews this important issue of complications associated with THA. Method: We looked into Electronic databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), the archives of meetings of orthopaedic associations and the bibliographies of included articles and asked experts to identify prospective studies, published in any language that evaluated intra-operative fractures occurring during total hip arthroplasty from the year 1950-2020. The screening, data extraction and quality assessment were carried out by two researchers and if there was any discrepancy, a third reviewer was involved. Fourteen studies were identified. The reported range of occurrence of fracture while performing hip replacement surgery was found to be 0.4-7.6%. Major risk factors identified were surgical approaches, Elderly age, less Metaphyseal-Diaphyseal Index score, change in resistance while insertion of the femur implants, inexperienced surgeons, uncemented femoral components, use of monoblock elliptical components, implantation of the acetabular components, patients with ankylosing spondylitis, female gender, uncemented stems in patients with abnormal proximal femoral anatomy and with cortices, different stem designs, heterogeneous fracture patterns and toothed design. Intraoperative fractures during THA were managed with cerclage wire, femoral revision, intramedullary nail and cerclage wires, use of internal fixation plates and screws for management of intra operative femur and acetabular fractures. The main reason for intraoperative fracture was found to be usage of cementless implants but planning and timely recognition of risk factors and evaluating them is important in management of intraoperative fractures. Adequate surgical site exposure is critical especially during dislocation of hip, reaming of acetabulum, impaction of implant and preparing the femoral canal for stem insertion. Eccentric and increased reaming of acetabulum to accommodate a larger cup is to be avoided, especially in females and elderly patients as the acetabulum is thinner. However, this area requires more research in order to obtain more evidence on effectiveness, safety and management of intraoperative fractures during THA

Low back pain is thought to relate to intervertebral disc (IVD) degeneration. Although the mechanisms have not been clearly identified, exhaustion of nucleus pulposus cells and their producing matrix is regarded as one cause. The matrix of the IVD is continuously replenished and remodeled by tissue-specialized cells and are crucial in supporting the IVD function. However, due to aging, trauma, and genetic and lifestyle factors, the cells can lose their potency and viability, thereby limiting their collective matrix production capacity. We have discovered the link between loss of angiopoietin-1 receptor (Tie2)-positive human NP progenitor cells (NPPC) and IVD degeneration. Tie2+ cells were characterized as undifferentiated cells with multipotency and possessing high self-renewal abilities. Thus we and others have proposed Tie2+ NPPC as a potent cell source for regenerative cell therapies against IVD degeneration. However, their utilization is hindered by low Tie2-expressing cell yields from NP tissue, in particular from commonly available older and degenerated tissue sources. Moreover, NPPC show a rapid Tie2 decrease due to cell differentiation as part of standard culture processes. As such, a need exists to optimize or develop new culture methods that enable the maintenance of Tie2-expressing NPPC. Trials to overcome these difficulties will be shared

Introduction. Femoral periprosthetic fractures above TKA are commonly treated with retrograde intramedullary nailing (IMN). This study determined if TKA design and liner type affect the minimum knee flexion required for retrograde nailing through a TKA. Methods. Twelve cadaveric specimens were prepared for six single radius (SR) TKAs and six asymmetric medial pivot (MP) TKAs. Trials with 9mm polyethylene liners were tested with cruciate retaining (CR), cruciate substituting (CS) and posterior stabilizing (PS) types. The knee was extended to identify the minimum knee flexion required to allow safe passage of the opening reamer while maintaining an optimal fluoroscopic starting point for retrograde nailing. Furthermore, the angle of axis deviation between the reamer and the femoral shaft was calculated from fluoroscopic images. Results. In all specimens, the reamer entry point was posterior to Blumensaat's line. In the SR TKA, the average flexion required was 70, 71 and 82 degrees for CR, CS and PS respectively. The required flexion in PS was significantly greater than the other designs (p=0.03). In the MP TKA, the average flexion required was 74, 84 and 123 degrees for CR, CS and PS respectively. The required flexion was significantly greater in CS and PS designs (p<0.0001). Femoral component size did not affect the minimum flexion required. Furthermore, the entry reamer required 9.2 (SR) and 12.5 (MP) degrees of posterior axis deviation from the femur. Conclusions. Our study illustrates four novel factors to consider when performing retrograde nailing through TKA. First, significant knee flexion is required to obtain an ideal radiographic starting point when retaining the liner. Second, PS implants require more flexion with both TKA designs. Third, femoral component size does not affect the flexion required. Fourth, there is a consistent posterior axis deviation of the entry reamer from the femoral shaft, explaining the commonly created extension deformity

Patients with osteoarthritis (OA) of the knee commonly alter their movement to compensate for deficiencies. This study presents a new numerical procedure for classifying sit-to-walk (STW) movement strategies. Ten control and twelve OA participants performed the STW task in a motion capture laboratory. A full body biomechanical model was used. Participants were instructed to sit in a comfortable self-selected position on a stool height adjusted to 100% of their knee height and then stand and pick up an object from a table in front of them. Three matrices were constructed defining the progression of the torso, feet and hands in the sagittal plane along with a fourth expressing the location of the hands relative to the knees. Hierarchical clustering (HC) was used to identify different strategies. Trials were also classified as to whether the left (L) and right (R) extremities used a matching strategy (bilateral) or not (asymmetrical). Fisher's exact test was used to compare this between groups. Clustering of the torso matrix dichotomised the trials in two major clusters; subjects leaning forward (LF) or not. The feet and hands matrices revealed sliding the foot backward (FB) and moving an arm forward (AF) strategies respectively. Trials not belonging in the AF cluster were submitted to the last HC of the fourth matrix exposing three additional strategies, the arm pushing through chair (PC), arm pushing through knee (PK) and arm not used (NA). The control participants used the LF+FBR+PK combination most frequently whereas the OA participants used the AFR+PCL. OA patients used significantly more asymmetrical arm strategies, p=0.034. The results demonstrated that control and OA participants favour different STW strategies. The OA patients asymmetrical arm behaviour possibly indicates compensating for weakness of the affected leg. These strategy definitions may be useful to assess post-operative outcomes and rehabilitation progress

Objectives. Our objective was to perform a systematic review of the literature and conduct a meta- analysis to investigate the effect of initial varus or valgus displacement of proximal humerus on the outcomes of patients with proximal humerus fractures treated with open reduction and internal fixation. Methods. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, we performed a systematic review. Electronic databases MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify randomised and non-randomised studies comparing postoperative outcomes associated with initial varus versus initial valgus displacement of proximal humerus fracture. The Newcastle–Ottawa scale was used to assess the methodological quality and risk of bias of the selected studies. Fixed-effect or random-effects models were applied to calculate pooled outcome data. Results. We identified two retrospective cohort studies and one retrospective analysis of a prospective database, enrolling a total of 243 patients with proximal humerus fractures. Our analysis showed that initial varus displacement was associated with a higher risk of overall complication (RR 2.28, 95% CI 1.12–4.64, P = 0.02), screw penetration (RR 2.30, 95% CI 1.06–5.02, P = 0.04), varus displacement (RR 4.38, 95% CI 2.22–8.65, P < 0.0001), and reoperation (RR 3.01, 95% CI 1.80–5.03, P < 0.0001) compared to valgus displacement. There was no significant difference in avascular necrosis (RR 1.43, 95% CI 0.62–3.27, P = 0.40), infection (RR 1.49, 95% CI 0.46–4.84, P = 0.51), and non-union or malunion (RR 1.37, 95% CI 0.37–5.04, P = 0.64). Conclusions. The best available evidence demonstrates that initial varus displacement of proximal humerus fractures is associated with higher risk of overall complication, screw penetration, varus displacement, and reoperation compared to initial valgus displacement. The best available evidence is not adequately robust to make definitive conclusions. Further high quality studies, that are adequately powered, are required to investigate the outcomes of initial varus and valgus displacement in specific fracture types

BACKGROUND. Diffuse noxious inhibitory control (DNIC) is impaired in people with chronic pain such as knee osteoarthritis (KOA), which may predict the risk of acute-to-chronic pain transition. Electroacupuncture (EA) is effective in relieving pain in patients with KOA. However, whether EA may inhibit acute-to-chronic pain transition of KOA has not been systematically examined. METHODS. This was a multicenter, three-arm parallel, single-blind randomized controlled trial involving a total of 450 patients with KOA. This study was approved by the Chinese Ethics Committee of Registering Clinical Trials (reference: ChiECRCT-20140035) and registered with Chinese Clinical Trial Registry (ChiCTR-ICR-14005411). Patients were divided into three groups based on EA current intensity: strong EA (>2mA), weak EA (<0.5mA) and sham EA (none acupoint). Treatments consisted of five sessions per week, for two weeks. Primary outcome measures were visual analog scale (VAS) and DNIC function. RESULTS. One week of EA had no clinical important improvement in VAS and DNIC function in all three groups (P>0.05). After 2 weeks” treatment, changes from baseline showed that VAS (strong EA: 2.97, SD 0.10, P<0.0001; weak EA: 2.75, SD 0.15, P <0.0001; sham EA: 1.19, SD 0.14, P<0.0001) and DNIC (strong EA: −14.85, SD 0.16, P<0.0001; weak EA: −4.75, SD 0.28, P<0.0001; sham EA: −1.43, SD 0.24, P<0.0001) were significantly improved in all three groups. Compared with sham EA, weak EA (3.8, 95%CI 3.45 to 4.15) and strong EA (13.54, 95%CI 13.23 to 13.85) were better in improving DNIC function. Compared with weak EA, strong EA were better in enhancing DNIC function (9.73, 95%CI 9.44 to 10.02), as well as in reducing VAS. CONCLUSIONS. In conclusion, EA should be administered 2 weeks to exerting significant effect on KOA. Strong EA was better than weak or sham EA in alleviating the intensity of pain and inhibiting the acute-to-chronic pain transition of KOA