Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
This single-centre observational study aimed to describe the results of extensive bone impaction grafting of the whole acetabular cavity in combination with an uncemented component in acetabular revisions performed in a standardized manner since 1993. Between 1993 and 2013, 370 patients with a median age of 72 years (interquartile range (IQR) 63 to 79 years) underwent acetabular revision surgery. Of these, 229 were more than ten years following surgery and 137 were more than 15 years. All revisions were performed with extensive use of morcellized allograft firmly impacted into the entire acetabular cavity, followed by insertion of an uncemented component with supplementary screw fixation. All types of reoperation were captured using review of radiographs and medical charts, combined with data from the local surgical register and the Swedish Hip Arthroplasty Register.Aims
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Osseointegrated prosthetic limbs allow better mobility than socket-mounted prosthetics for lower limb amputees. Fractures, however, can occur in the residual limb, but they have rarely been reported. Approximately 2% to 3% of amputees with socket-mounted prostheses may fracture within five years. This is the first study which directly addresses the risks and management of periprosthetic osseointegration fractures in amputees. A retrospective review identified 518 osseointegration procedures which were undertaken in 458 patients between 2010 and 2018 for whom complete medical records were available. Potential risk factors including time since amputation, age at osseointegration, bone density, weight, uni/bilateral implantation and sex were evaluated with multiple logistic regression. The mechanism of injury, technique and implant that was used for fixation of the fracture, pre-osseointegration and post fracture mobility (assessed using the K-level) and the time that the prosthesis was worn for in hours/day were also assessed.Aims
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The purpose of this study was to determine whether intracellular After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged Aims
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It is uncertain whether instrumented spinal fixation in nonambulatory children with neuromuscular scoliosis should finish at L5 or be extended to the pelvis. Pelvic fixation has been shown to be associated with up to 30% complication rates, but is regarded by some as the standard for correction of deformity in these conditions. The incidence of failure when comparing the most caudal level of instrumentation, either L5 or the pelvis, using all-pedicle screw instrumentation has not previously been reported. In this retrospective study, we compared nonambulatory patients undergoing surgery at two centres: one that routinely instrumented to L5 and the other to the pelvis. In all, 91 nonambulatory patients with neuromuscular scoliosis were included. All underwent surgery using bilateral, segmental, pedicle screw instrumentation. A total of 40 patients underwent fusion to L5 and 51 had their fixation extended to the pelvis. The two groups were assessed for differences in terms of clinical and radiological findings, as well as complications.Aims
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The aim of this study was to assess whether supine flexibility predicts the likelihood of curve progression in patients with adolescent idiopathic scoliosis (AIS) undergoing brace treatment. This was a retrospective analysis of patients with AIS prescribed with an underarm brace between September 2008 to April 2013 and followed up until 18 years of age or required surgery. Patients with structural proximal curves that preclude underarm bracing, those who were lost to follow-up, and those who had poor compliance to bracing (<16 hours a day) were excluded. The major curve Cobb angle, curve type, and location were measured on the pre-brace standing posteroanterior (PA) radiograph, supine whole spine radiograph, initial in-brace standing PA radiograph, and the post-brace weaning standing PA radiograph. Validation of the previous in-brace Cobb angle regression model was performed. The outcome of curve progression post-bracing was tested using a logistic regression model. The supine flexibility cut-off for curve progression was analyzed with receiver operating characteristic curve.Aims
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Arthroplasty for end-stage hallux rigidus (HR) is controversial. Arthrodesis remains the gold standard for surgical treatment, although is not without its complications, with rates of up to 10% for nonunion, 14% for reoperation and 10% for metatarsalgia. The aim of this study was to analyze the outcome of a double-stemmed silastic implant (Wright-Medical, Memphis, Tennessee, USA) for patients with end-stage HR. We conducted a retrospective review of 108 consecutive implants in 76 patients, between January 2005 and December 2016, with a minimum follow-up of two years. The mean age of the patients at the time of surgery was 61.6 years (42 to 84). There were 104 females and four males. Clinical, radiological, patient reported outcome measures (PROMS) data, a visual analogue score (VAS) for pain, and satisfaction scores were collected.Aims
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Accurate measurement of the glenoid version is important in performing total shoulder arthroplasty (TSA). Our aim was to evaluate the Ellipse method, which involves formally defining the vertical mid-point of the glenoid prior to measuring the glenoid version and comparing it with the ‘classic’ Friedman method. This was a retrospective study which evaluated 100 CT scans for patients who underwent a primary TSA. The glenoid version was measured using the Friedman and Ellipse methods by two senior observers. Statistical analyses were performed using the paired Aims
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Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called ‘stem cell’ preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers. Cite this article:
To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation.Aims
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Although good clinical outcomes have been reported for monolithic tapered, fluted, titanium stems (TFTS), early results showed high rates of subsidence. Advances in stem design may mitigate these concerns. This study reports on the use of a current monolithic TFTS for a variety of indications. A multi-institutional retrospective study of all consecutive total hip arthroplasty (THA) and revision total hip arthroplasty (rTHA) patients who received the monolithic TFTS was conducted. Surgery was performed by eight fellowship-trained arthroplasty surgeons at four institutions. A total of 157 hips in 153 patients at a mean follow-up of 11.6 months (SD7.8) were included. Mean patient age at the time of surgery was 67.4 years (SD 13.3) and mean body mass index (BMI) was 28.9 kg/m2 (SD 6.5). Outcomes included intraoperative complications, one-year all-cause re-revisions, and subsidence at postoperative time intervals (two weeks, six weeks, six months, nine months, and one year).Aims
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To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17).Aims
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We aimed to examine the long-term mechanical survivorship, describe the modes of all-cause failure, and identify risk factors for mechanical failure of all-polyethylene tibial components in endoprosthetic reconstruction. This is a retrospective database review of consecutive endoprosthetic reconstructions performed for oncological indications between 1980 and 2019. Patients with all-polyethylene tibial components were isolated and analyzed for revision for mechanical failure. Outcomes included survival of the all-polyethylene tibial component, revision surgery categorized according to the Henderson Failure Mode Classification, and complications and functional outcome, as assessed by the Musculoskeletal Tumor Society (MSTS) score at the final follow-up.Aims
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Complex displaced osteoporotic acetabular fractures in the elderly are associated with high levels of morbidity and mortality. Surgical options include either open reduction and internal fixation alone, or combined with total hip arthroplasty (THA). There remains a cohort of severely comorbid patients who are deemed unfit for extensive surgical reconstruction and are treated conservatively. We describe the results of a coned hemipelvis reconstruction and THA inserted via a posterior approach to the hip as the primary treatment for this severely high-risk cohort. We have prospectively monitored a series of 22 cases (21 patients) with a mean follow-up of 32 months (13 to 59).Aims
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To evaluate the donor site morbidity and tendon morphology after harvesting whole length, full-thickness peroneus longus tendon (PLT) proximal to the lateral malleolus for ligament reconstructions or tendon transfer. A total of 21 eligible patients (mean age 34.0 years (standard deviation (SD) 11.2); mean follow-up period 31.8 months (SD 7.7), and 12 healthy controls (mean age, 26.8 years (SD 5.9) were included. For patients, clinical evaluation of the donor ankle was performed preoperatively and postoperatively. Square hop test, ankle strength assessment, and MRI of distal calf were assessed bilaterally in the final follow-up. The morphological symmetry of peroneal tendons bilaterally was evaluated by MRI in healthy controls.Aims
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Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls. We included 78 adolescents with idiopathic scoliosis (57 female patients) at a mean age of 13.7 years (8.5 to 19.6) and 52 age- and sex-matched healthy controls (39 female patients) at a mean age of 13.8 years (9.1 to 17.6). Mean skeletal age, estimated according to the Tanner-Whitehouse 3 system (TW3), was 13.4 years (7.4 to 17.8) for those with idiopathic scoliosis, and 13.1 years (7.4 to 16.5) for the controls. Mean Cobb angle for those with idiopathic scoliosis was 29° (SD 11°). All individuals were scanned with dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) of the left radius and tibia to assess bone density. Statistical analyses were performed with independent-samples Aims
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Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly. This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes.Aims
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The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis. In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years’ follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded.Aims
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The aim of this study was to explore whether time to surgery affects functional outcome in displaced proximal humeral fractures A total of 250 patients presenting within three weeks of sustaining a displaced proximal humeral fracture involving the surgical neck were recruited at 32 acute NHS hospitals in the United Kingdom between September 2008 and April 2011. Of the 125 participants, 109 received surgery (fracture fixation or humeral head replacement) as per randomization. Data were included for 101 and 67 participants at six-month and five-year follow-up, respectively. Oxford Shoulder Scores (OSS) collected at six, 12, and 24 months and at three, four, and five years following randomization was plotted against time to surgery. Long-term recovery was explored by plotting six-month scores against five-year scores and agreement was illustrated with a Bland-Altman plot.Aims
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To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways.Aims
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Limited evidence is available on mid-term outcomes of robotic-arm assisted (RA) partial knee arthroplasty (PKA). Therefore, the purpose of this study was to evaluate mid-term survivorship, modes of failure, and patient-reported outcomes of RA PKA. A retrospective review of patients who underwent RA PKA between June 2007 and August 2016 was performed. Patients received a fixed-bearing medial or lateral unicompartmental knee arthroplasty (UKA), patellofemoral arthroplasty (PFA), or bicompartmental knee arthroplasty (BiKA; PFA plus medial UKA). All patients completed a questionnaire regarding revision surgery, reoperations, and level of satisfaction. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed using the KOOS for Joint Replacement Junior survey.Aims
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Intraoperative 3D navigation (ION) allows high accuracy to be achieved in spinal surgery, but poor workflow has prevented its widespread uptake. The technical demands on ION when used in patients with adolescent idiopathic scoliosis (AIS) are higher than for other more established indications. Lean principles have been applied to industry and to health care with good effects. While ensuring optimal accuracy of instrumentation and safety, the implementation of ION and its associated productivity was evaluated in this study for AIS surgery in order to enhance the workflow of this technique. The aim was to optimize the use of ION by the application of lean principles in AIS surgery. A total of 20 consecutive patients with AIS were treated with ION corrective spinal surgery. Both qualitative and quantitative analysis was performed with real-time modifications. Operating time, scan time, dose length product (measure of CT radiation exposure), use of fluoroscopy, the influence of the reference frame, blood loss, and neuromonitoring were assessed.Aims
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The aim of this study was to identify the effect of the manufacturing characteristics of polyethylene acetabular liners on the survival of cementless and hybrid total hip arthroplasty (THA). Prospective cohort study using linked National Joint Registry (NJR) and manufacturer data. The primary endpoint was revision for aseptic loosening. Cox proportional hazard regression was the primary analytical approach. Manufacturing variables included resin type, crosslinking radiation dose, terminal sterilization method, terminal sterilization radiation dose, stabilization treatment, total radiation dose, packaging, and face asymmetry. Total radiation dose was further divided into G1 (no radiation), G2 (> 0 Mrad to < 5 Mrad), G3 (≥ 5 Mrad to < 10 Mrad), and G4 (≥ 10 Mrad).Aims
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It is unknown whether kinematic alignment (KA) objectively improves knee balance in total knee arthroplasty (TKA), despite this being the biomechanical rationale for its use. This study aimed to determine whether restoring the constitutional alignment using a restrictive KA protocol resulted in better quantitative knee balance than mechanical alignment (MA). We conducted a randomized superiority trial comparing patients undergoing TKA assigned to KA within a restrictive safe zone or MA. Optimal knee balance was defined as an intercompartmental pressure difference (ICPD) of 15 psi or less using a pressure sensor. The primary endpoint was the mean intraoperative ICPD at 10° of flexion prior to knee balancing. Secondary outcomes included balance at 45° and 90°, requirements for balancing procedures, and presence of tibiofemoral lift-off.Aims
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Distal radial fractures are the most common fracture sustained by the adult population. Most can be treated using cast immobilization without the need for surgery. The aim of this study was to assess the feasibility of a definitive trial comparing the commonly used fibreglass cast immobilization with an alternative product called Woodcast. Woodcast is a biodegradable casting material with theoretical benefits in terms of patient comfort as well as benefits to the environment. This was a multicentre, two-arm, open-label, parallel-group randomized controlled feasibility trial. Patients with a fracture of the distal radius aged 16 years and over were recruited from four centres in the UK and randomized (1:1) to receive a Woodcast or fibreglass cast. Data were collected on participant recruitment and retention, clinical efficacy, safety, and patient acceptability.Aims
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Carpal malalignment after a distal radial fracture occurs due to loss of volar tilt. Several studies have shown that this has an adverse influence on function. We aimed to investigate the magnitude of dorsal tilt that leads to carpal malalignment, whether reduction of dorsal tilt will correct carpal malalignment, and which measure of carpal malalignment is the most useful. Radiographs of patients with a distal radial fracture were prospectively collected and reviewed. Measurements of carpal malalignment were recorded on the initial radiograph, the radiograph following reduction of the fracture, and after a further interval. Linear regression modelling was used to assess the relationship between dorsal tilt and carpal malalignment. Receiver operating characteristic (ROC) analysis was used to identify which values of dorsal tilt led to carpal malalignment.Aims
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The aim of this study was to report our experience at 3.5 years with outpatient total hip arthroplasty (THA). In this prospective cohort study, we included all patients who were planned to receive primary THA through the anterior approach between 1 April 2014 and 1 October 2017. Patient-related data and surgical information were recorded. Patient reported outcome measures (PROMs) related to the hip and an anchor question were taken preoperatively, at six weeks, three months, and one year after surgery. All complications, readmissions, and reoperations were registered.Aims
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Debate continues about whether it is better to use a cemented or uncemented hemiarthroplasty to treat a displaced intracapsular fracture of the hip. The aim of this study was to attempt to resolve this issue for contemporary prostheses. A total of 400 patients with a displaced intracapsular fracture of the hip were randomized to receive either a cemented polished tapered stem hemiarthroplasty or an uncemented Furlong hydroxyapatite-coated hemiarthroplasty. Follow-up was conducted by a nurse blinded to the implant at set intervals for up to one year from surgery.Aims
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The purpose of this study was to report the long-term results of extendable endoprostheses of the humerus in children after the resection of a bone sarcoma. A total of 35 consecutive patients treated with extendable endoprosthetic replacement of the humerus in children were included. There were 17 boys and 18 girls in the series with a median age at the time of initial surgery of nine years (interquartile range (IQR) 7 to 11).Aims
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The aim of this study was to develop a psychometrically sound measure of recovery for use in patients who have suffered an open tibial fracture. An initial pool of 109 items was generated from previous qualitative data relating to recovery following an open tibial fracture. These items were field tested in a cohort of patients recovering from an open tibial fracture. They were asked to comment on the content of the items and structure of the scale. Reduction in the number of items led to a refined scale tested in a larger cohort of patients. Principal components analysis permitted further reduction and the development of a definitive scale. Internal consistency, test-retest reliability, and responsiveness were assessed for the retained items.Aims
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Trochlear dysplasia is a significant risk factor for patellofemoral instability. The Dejour classification is currently considered the standard for classifying trochlear dysplasia, but numerous studies have reported poor reliability on both plain radiography and MRI. The severity of trochlear dysplasia is important to establish in order to guide surgical management. We have developed an MRI-specific classification system to assess the severity of trochlear dysplasia, the Oswestry-Bristol Classification (OBC). This is a four-part classification system comprising normal, mild, moderate, and severe to represent a normal, shallow, flat, and convex trochlear, respectively. The purpose of this study was to assess the inter- and intraobserver reliability of the OBC and compare it with that of the Dejour classification. Four observers (two senior and two junior orthopaedic surgeons) independently assessed 32 CT and axial MRI scans for trochlear dysplasia and classified each according to the OBC and the Dejour classification systems. Assessments were repeated following a four-week interval. The inter- and intraobserver agreement was determined by using Fleiss’ generalization of Cohen’s kappa statistic and S-statistic nominal and linear weights.Aims
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Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. We investigated the specific role of GNAQ using Aims
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The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes. Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro.Aims
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Patient engagement in adaptive health behaviours and interactions with their healthcare ecosystem can be measured using self-reported instruments, such as the Patient Activation Measure (PAM-13) and the Effective Consumer Scale (ECS-17). Few studies have investigated the influence of patient engagement on limitations (patient-reported outcome measures (PROMs)) and patient-reported experience measures (PREMs). First, we assessed whether patient engagement (PAM-13, ECS-17) within two to four weeks of an upper limb fracture was associated with limitations (the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), and Patient-Reported Outcome Measurement Information System Upper Extremity Physical Function computer adaptive test (PROMIS UE PF) scores) measured six to nine months after fracture, accounting for demographic, clinical, and psychosocial factors. Secondly, we assessed the association between patient engagement and experience (numerical rating scale for satisfaction with care (NRS-C) and satisfaction with services (NRS-S) six to nine months after fracture. A total of 744 adults with an isolated fracture of the proximal humerus, elbow, or distal radius completed PROMs. Due to multicollinearity of patient engagement and psychosocial variables, we generated a single variable combining measures of engagement and psychosocial factors using factor analysis. We then performed multivariable analysis with p < 0.10 on bivariate analysis.Aims
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