Ceramic-on-Ceramic Total Hip Arthroplasty and Noises: A Prospective Blinded Randomized Controlled Trial of Influence of Component Design.

BACKGROUND: Noises have been associated with ceramic-on-ceramic bearings in total hip arthroplasties. The etiology is multifactorial, but a high prevalence of noises was reported in studies using a specific acetabular component system. We examined if specific ceramic component designs are associated with the prevalence of noises in 2 commonly used component systems. We hypothesized that there would be no difference in noises between the 2 systems. METHODS: In this randomized controlled trial, 2 different component designs with ceramic bearings were compared. Inclusion criteria were primary total hip arthroplasties, age between 18 and 65 years, and body mass index less than 35. The primary outcome was prevalence of noises, whereas secondary outcomes consisted of European Quality of Life index, visual analog scale, and University of California and Los Angeles activity scale. Follow-up data were collected at 3 and 12 months postoperatively. Data were available for 91 patients in Group 1 and for 92 patients in Group 2. Preoperative patient characteristics were comparable between groups. RESULTS: At 12-month follow-up, the prevalence of noises was 19% in Group 1 and 14% in Group 2 (P = .41). European Quality of Life index were 0.89 in Group 1 versus 0.90 in Group 2 (P = .42). The visual analog scale was 81 in both groups (P = .88). When evaluating level of activity, University of California and Los Angeles activity scale scores were 8.2 in both groups (P = .92). CONCLUSION: At 12-month follow-up, there was no difference in the prevalence of noises between the 2 component designs.

Clinical investigations to evaluate high-risk orthopaedic devices: a systematic review of the peer-reviewed medical literature.

Purpose: The objective of this systematic review was to give an overview of clinical investigations regarding hip and knee arthroplasty implants published in peer-reviewed scientific medical journals before entry into force of the EU Medical Device Regulation in May 2021. Methods: We systematically reviewed the medical literature for a random selection of hip and knee implants to identify all peer-reviewed clinical investigations published within 10 years before and up to 20 years after regulatory approval. We report study characteristics, methodologies, outcomes, measures to prevent bias, and timing of clinical investigations of 30 current implants. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: We identified 2912 publications and finally included 151 papers published between 1995 and 2021 (63 on hip stems, 34 on hip cups, and 54 on knee systems). We identified no clinical studies published before Conformité Européene (CE)-marking for any selected device, and no studies even up to 20 years after CE-marking in one-quarter of devices. There were very few randomized controlled trials, and registry-based studies generally had larger sample sizes and better methodology. Conclusion: The peer-reviewed literature alone is insufficient as a source of clinical investigations of these high-risk devices intended for life-long use. A more systematic, efficient, and faster way to evaluate safety and performance is necessary. Using a phased introduction approach, nesting comparative studies of observational and experimental design in existing registries, increasing the use of benefit measures, and accelerating surrogate outcomes research will help to minimize risks and maximize benefits.

High dose dexamethasone in high pain responders undergoing total hip arthroplasty: A randomized controlled trial.

BACKGROUND: Postoperative pain after total hip arthroplasty (THA) may delay postoperative mobilization and discharge. Postoperative pain has been shown to be higher in pain catastrophisers and patients receiving opioids. A single dose of glucocorticoid reduces pain after THA, and an increased dose of glucocorticoids has been found to be effective in patients at high risk of postoperative pain after total knee arthroplasty (TKA), however, the ideal dose in THA remains unknown. OBJECTIVE: To evaluate the effect of a high dose (1 mg kg -1 ) vs. intermediate dose (0.3 mg kg -1 ) of dexamethasone on pain after THA. DESIGN: A randomized double-blind controlled study. SETTING: A two-centre study including two large arthroplasty sites in Denmark was conducted from February 2019 to August 2020. PATIENTS: A total of 160 patients undergoing THA by neuraxial block with multimodal analgesia, having a Pain Catastrophising Scale score >20 and/or preoperative opioid use were included. INTERVENTION: Patients were randomly assigned to receive dexamethasone 1 mg kg -1 or 0.3 mg kg -1 before THA. MAIN OUTCOME MEASURES: Primary outcome was percentage of patients experiencing moderate to severe pain (visual analogue scale, VAS > 30 mm on a 0 to 100 mm scale) on ambulating 24 h after surgery. Secondary outcomes included cumulated pain scores, C-reactive protein (CRP), opioid use, postoperative recovery scores, length of stay, complications, and re-admission within 30 and 90 days. RESULTS: No difference was found in percentage of VAS >30 mm 24 h after surgery in the 5-m walk test (VAS > 30/VAS ≤ 30%); 33/42 (44%) vs. 32/43 (43%), relative risk = 1.04 (95% confidence interval 0.72-1.51; P  = 0.814) in 1 mg kg -1vs. 0.3 mg kg -1 respectively. No differences were found in CRP and opioid use between groups. Also, no intergroup differences were found in recovery scores, re-admissions, or complications. CONCLUSION: 1 mg kg -1vs. 0.3 mg kg -1 dexamethasone improved neither postoperative pain nor recovery in THA in a cohort of predicted high pain responders. TRIAL REGISTRATION: ClinicalTrials.gov ID-number NCT03763760 and EudraCT-number 2018-2636-25.

Repeat dose steroid in high pain responders after total knee arthroplasty: A study protocol.

Pain after total knee arthroplasty (TKA) is a well-known clinical problem potentially delaying ambulation and recovery. Perioperative glucocorticoids reduce pain and facilitate early recovery, but the optimal timing and dose are still unknown. High pain catastrophizers have an increased risk of poorly controlled postoperative pain, and moderate to severe pain at 24 h is associated with a risk of pain relapse at 48 h. To evaluate the effect of a repeat moderate dose of glucocorticoids after TKA in high pain catastrophizers presenting with moderate to severe pain 24 h postoperatively, having received preoperative high-dose glucocorticoids. High pain catastrophizers (Pain Catastrophizing Scale > 20) undergoing TKA are screened 24 h postoperatively and are included if they experience moderate to severe pain (VAS > 30) during a 5 m walk test. The included patients will receive either oral 24 mg dexamethasone (n = 55) or placebo (n = 55) on the evening of Day 1 (~30-37 h) after surgery. In addition, patients receive a standard multimodal analgesic regimen, including paracetamol, celecoxib, local infiltration analgesia, and preoperative dexamethasone (1 mg/kg). Patients will fill out a pain diary for 7 days after surgery. The primary outcome is moderate to severe pain (VAS > 30) during a 5 m walk test on the morning of Day 2 after surgery. The secondary outcomes include cumulated pain at rest and during ambulation, cumulated use of rescue analgesics, quality of sleep, lethargy, dizziness, nausea, satisfaction with the analgesic regimen, length of stay, morbidity, mortality, and reasons for readmissions. Follow-up is at 8 and 30 days. The data from this study will provide evidence for the effect of a repeated dose of dexamethasone as an analgesic adjuvant in patients undergoing TKA with a high risk of postoperative pain.

High-dose dexamethasone in low pain responders undergoing total knee arthroplasty: a randomised double-blind trial.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) is a continuing problem despite optimised multimodal analgesia. Previous studies have shown preoperative glucocorticoids to reduce postoperative pain, but knowledge about specific doses and effects in specific patient groups is lacking. METHODS: A two-centre, double-blind, two-arm study comparing preoperative dexamethasone (1 mg kg-1vs 0.3 mg kg-1 i.v.) on postoperative pain in 160 planned TKA subjects with low preoperative pain catastrophising and no opioid use. Subjects received multimodal analgesia with paracetamol, cyclooxygenase-2 inhibitors, local anaesthetic infiltration analgesia, and rescue opioids. The primary outcome was percentage of subjects experiencing moderate to severe pain (visual analogue scale >30 mm) upon ambulation at 24 h. Secondary outcomes included pain scores, postoperative inflammation (C-reactive protein), opioid and antiemetics use, and 'Quality of Recovery-15' and 'Opioid-Related Symptom Distress Scale', length of stay, readmissions, and complications up to Day 90. RESULTS: A total of 157 subjects (80 vs 77) were included. No difference was found between groups in the incidence of subjects experiencing visual analogue scale >30 on ambulation 24 h after surgery (56% vs 53%, relative risk =1.07, confidence interval: 0.8-1.4, P=0.65). No differences in other pain outcomes or use of rescue opioids and antiemetics, in Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, length of stay, readmissions, or complications. C-reactive protein values were comparable at 24 h (13 [6-25] mg L-1vs 16 [9-38] mg L-1, P = 0.07), but lower at 48 h (26 [9-52] mg L-1vs 50 [30-72] mg L-1, P<0.01) in the high-dose group. CONCLUSION: Use of 1 mg kg-1vs 0.3 mg kg-1 i.v. dexamethasone in low pain responders after TKA did not improve early postoperative pain or other outcomes in contrast to benefits in a high pain responder population. CLINICAL TRIAL REGISTRATION: NCT03758170 (first registration 29-11-2018).

High-dose steroids in high pain responders undergoing total knee arthroplasty: a randomised double-blind trial.

BACKGROUND: Total knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite multimodal opioid-sparing analgesia. Pain catastrophising or preoperative opioid therapy is associated with increased postoperative pain. Preoperative glucocorticoid improves pain after TKA, but dose-finding studies and benefit in high pain responders are lacking. METHODS: A randomised double-blind controlled trial with preoperative high-dose intravenous dexamethasone 1 mg kg-1 or intermediate-dose dexamethasone 0.3 mg kg-1 in 88 patients undergoing TKA with preoperative pain catastrophising score >20 or regular opioid use was designed. The primary outcome was the proportion of patients experiencing moderate-to-severe pain (VAS >30) during a 5 m walk 24 h postoperatively. Secondary outcomes included pain at rest during nights and at passive leg raise, C-reactive protein, opioid use, quality of sleep, Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, readmission, and complications. RESULTS: Moderate-to-severe pain when walking 24 h postoperatively was reduced (high dose vs intermediate dose, 49% vs 79%; P<0.01), along with pain at leg raise at 24 and 48 h (14% vs 29%, P=0.02 and 12% vs 31%, P=0.03, respectively). C-reactive protein was reduced in the high-dose group at both 24 and 48 h (both P<0.01). Quality of Recovery-15 was also improved (P<0.01). CONCLUSIONS: When compared with preoperative dexamethasone 0.3 mg kg-1 i.v., dexamethasone 1 mg kg-1 reduced moderate-to-severe pain 24 h after TKA and improved recovery in high pain responders without apparent side-effects. CLINICAL TRIAL REGISTRATION: NCT03763734.

EFORT recommendations for off-label use, mix & match and mismatch in hip and knee arthroplasty.

Off-label use is frequently practiced in primary and revision arthroplasty, as there may be indications for the application of implants for purposes outside the one the manufacturers intended.Under certain circumstances, patients may benefit from selective application of mix & match. This can refer to primary hip arthroplasty (if evidence suggests that the combination of devices from different manufacturers has superior results) and revision hip or knee arthroplasty (when the exchange of one component only is necessary and the invasiveness of surgery can be reduced).Within the EFORT 'Implant and Patient Safety Initiative', evidence- and consensus-based recommendations have been developed for the safe application of off-label use and mix & match in primary as well as revision hip and knee arthroplasty.Prior to the application of a medical device for hip or knee arthroplasty off-label and within a mix & match situation, surgeons should balance the risks and benefits to the patient, obtain informed consent, and document the decision process appropriately.Nevertheless, it is crucial for surgeons to only combine implants that are compatible. Mismatch of components, where their sizes or connections do not fit, may have catastrophic effects and is a surgical mistake.Surgeons must be fully aware of the features of the components that they use in off-label indications or during mix & match applications, must be appropriately trained and must audit their results.Considering the frequent practice of off-label and mix & match as well as the potential medico-legal issues, further research is necessary to obtain more data about the appropriate indications and outcomes for those procedures. Cite this article: EFORT Open Rev 2021;6:982-1005. DOI: 10.1302/2058-5241.6.210080.

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices).

In the European Union (EU), the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, while authorising the placing on the market of medical devices is decentralised to independent 'conformity assessment' organisations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the Medical Device Directive, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details - which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024. Here, we describe how it may contribute to the development of regulatory science in Europe. Cite this article: EFORT Open Rev 2021;6:839-849. DOI: 10.1302/2058-5241.6.210081.

Preoperative high-dose Steroids in Total Knee and Hip Arthroplasty - Protocols for three randomized controlled trials.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA)/ total hip arthroplasty (THA) still experience moderate-severe postoperative pain despite optimized pain management regimes. The patients already on opioid treatment and pain catastrophizers (PCs) have a higher risk of postoperative pain. The use of preoperative intravenous high-dose glucocorticoids decreases postoperative pain after TKA and THA, but optimal dose is yet to be found, and the effect on subpopulations at high pain risk is unknown. AIM: To investigate the effect of a higher than previously used dose of glucocorticoids (dexamethasone (DXM)), administered intravenously before surgery, as part of standardized fast-track regimen, on postoperative pain in TKA/THA subgroups. METHOD: Three separate randomized, double-blinded, controlled trials were planned to compare a new higher dose DXM (1 mg/kg) to the earlier used high-dose DXM (0.3 mg/kg). Study 1: predicted Low Pain TKA; study 2: predicted High Pain Responder (HPR) TKA; study 3: predicted HPR THA. Predicted HPR groups consist of either PCs with PCS-score of ≥ 21 and/or history of ongoing opioid-treatment of 30 mg/day of morphine or equivalents > 30 days. In total, 408 patients were planned for inclusion (160 Low Pain TKA, 88 HPR TKA, 160 HPR THA). PRIMARY OUTCOME: Pain upon ambulation in a 5-meter walk test 24 hours after surgery. Secondary outcomes include use of analgesics, rescue-opioids, antiemetics, cumulated pain, CRP, OR-SDS, QoR-15, quality of sleep, length of stay (LOS), reasons for hospitalization, readmission, morbidity, and mortality. Patients completed follow-up on day 90. Recruiting commenced February 2019 and is expected to finish in September 2020.

Survival and revision causes of hip resurfacing arthroplasty and the Mitch proximal epiphyseal replacement: results from the Danish Hip Arthroplasty Register.

Background and purpose - The Mitch proximal epiphyseal replacement (PER) was developed to preserve proximal femoral bone and minimize femoral neck fracture associated with hip resurfacing arthroplasty (HRA). We studied the survival and risk of revision of HRA compared with cementless metal-on-polyethylene (MoP) total hip arthroplasty (THA) and the survival and risk of revision of the Mitch PER compared with MoP THA.Patients and methods - Using propensity score, we matched 1,057 HRA to 1,057 MoP THA and 202 Mitch PER to 1,010 MoP THA from the Danish Hip Arthroplasty Register. To estimate the relative risk (RR) of revision, we used regression with the pseudo-value approach and treated death as a competing risk.Results - The cumulative incidence for any revision of HRA at 10 years' follow-up was 11% (95% confidence interval [CI] 9.1-13) and 6.4% (CI 5.8-7.0) for MoP THA. The RR of any revision was 1.5 (CI 1.1-2.1) for HRA at 10 years' follow-up. By excluding the ASR components, the RR of revision at 10 years was 1.2 (CI 0.8-1.7). The cumulative incidence of revision was 9.6% (CI 4.2-18) for Mitch PER and 5.4% (CI 5.1-5.7) for MoP THA at 8 years. The RR of revision was 2.0 (CI 0.9-4.3) for Mitch PER at 8 years' follow-up.Interpretation - The HRA had increased risk of revision compared with the MoP THA. When excluding ASR, the HRA group had similar risk of revision compared with MoP THA. The Mitch PER did not have a statistically significant increased risk of revision compared with MoP THA.

Catabolic activity of osteoblast lineage cells contributes to osteoclastic bone resorption in vitro.

Osteoblast lineage cells in human bone were recently shown to colonize eroded bone surfaces and to closely interact with osteoclasts. They proved to be identical to reversal cells and are believed to differentiate into bone-forming osteoblasts thereby coupling resorption and formation. However, they also exert catabolic activity that contributes to osteoclastic bone resorption, but this has not received much attention. Herein, we used co-cultures of primary human osteoblast lineage cells and human osteoclasts derived from peripheral blood monocytes to investigate whether a catabolic activity of osteoblast lineage cells could impact on osteoclastic bone resorption. Through a combination of immunofluorescence, in situ hybridization and time-lapse experiments, we show that MMP-13-expressing osteoblast lineage cells are attracted to and closely interact with bone-resorbing osteoclasts. This close interaction results in a strong and significant increase in the bone resorptive activity of osteoclasts - especially those making trenches. Importantly, we show that osteoclastic bone resorption becomes sensitive to inhibition of matrix metalloproteinases in the presence, but not in the absence, of osteoblast lineage cells. We propose that this may be due to the direct action of osteoblast-lineage-derived MMP-13 on bone resorption.

Complications and readmissions following outpatient total hip and knee arthroplasty: a prospective 2-center study with matched controls.

Background and purpose - Outpatient arthroplasty has gained popularity in recent years; however, safety concerns still remain regarding complications and readmissions. In a prospective 2-center study we investigated early readmissions with overnight stay and complications following outpatient total hip (THA) and total knee arthroplasty (TKA) compared with a matched patient cohort with at least 1 postoperative night in hospital. Patients and methods - All consecutive and unselected patients scheduled for THA or TKA at 2 participating hospitals were screened for potential day of surgery (DOS) discharge. Patients who fulfilled the DOS discharge criteria were discharged home. Patients discharged on DOS were matched on preoperative characteristics using propensity scores to patients operated at the same 2 departments prior to the beginning of this study with at least 1 overnight stay. All readmissions within 90 days were identified. Results - It was possible to match 116 of 138 outpatients with 339 inpatient controls. Median LOS in the control cohort was 2 days (1-9). 7 (6%) outpatients and 13 (4%) inpatient controls were readmitted within 90 days. Readmissions occurred between postoperative day 2-48 and day 4-58 in the outpatient and control cohorts, respectively. Importantly, we found no readmissions within the first 48 hours and no readmissions were related to the DOS discharge. Interpretation - Readmission rates in patients discharged on DOS may be similar to matched patients with at least 1 overnight stay. With the selection criteria used, there may be no safety signal associated with same-day discharge.

Patients' experiences during the first 12 weeks after discharge in fast-track hip and knee arthroplasty - a qualitative study.

BACKGROUND: Due to the shortened length of stay in fast-track total hip and knee arthroplasty, patients must at a very early stage following surgery take responsibility for their postoperative care and treatment. It is important to establish if this treatment modality of fast-track is not only cost-effective, but meets patients' expectations and needs. AIM: To explore the lived experience of patients in fast-track total hip and knee arthroplasty during the first 12 weeks after discharge. METHODS: A phenomenological-hermeneutic approach was used inspired by Ricoeur's theory of narrative and interpretation. Data were collected through semi-structured interviews with 8 patients 2 and 12 weeks after discharge. FINDINGS: Through the structural analysis 3 themes emerged: 1) Dealing with transition between hospital and home, 2) Pain and self-management of medication, 3) Challenges in rehabilitation. CONCLUSION: Patients appreciated only 1 or 2 days in hospital. However, they were not sufficiently involved in the discharge planning. There was a feeling of uncertainty and being left on their own after discharge, which could affect their pain management and recovery at home. There is a need to develop in partnership with each individual patient a post discharge plan of care and rehabilitation to meet their individual needs, preferences and mode of motivation.

5-year clinical and radiographic follow-up of the uncemented Symax hip stem in an international study.

BACKGROUND: The uncemented Symax hip stem is developed through optimization of the uncemented Omnifit hip stem. The Symax stem design combines an anatomical anteverted proximal geometry with a straight distal section. The proximal part is coated with a biomimetic hydroxyapatite (HA) coating for improved osseointegration to enhance load transfer and to minimize proximal bone loss. The distal part is treated with an anodization surface treatment in order to prevent distal bone apposition, which is expected to prevent distal loading and reduce proximal stress shielding. Aim of this study is to report mid-term clinical performance and evaluate whether the radiographic features are in line with the design principles of the Symax hip. METHODS: The biomimetic hydroxyapatite-coated uncemented Symax hip stem was evaluated in 80 patients during a 5-year prospective clinical international study. Harris Hip Score (HHS), Oxford Hip Score (OHS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were performed preoperatively and postoperatively at 6 months and 1, 2, 3 and 5 years. Anteroposterior radiographs of the pelvis and axial radiographs of the operated hips were evaluated immediately postoperative and at follow-up 6 months and 1, 2, 3, and 5 years. Wilcoxon signed-rank test was used to analyse whether clinical outcome scores changed statistically significant over time. The overall percentage of agreement between two radiology assessment teams was used to evaluate observer agreement of radiology results. The Cohen's Kappa was evaluated as a measure of reliability to quantify the agreement between raters, corrected for chance agreement. RESULTS: Clinical outcome scores were excellent at 5 years with mean HHS of 98.1, mean OHS of 16.2 and mean WOMAC of 6.9. Only 2.7% of the patients had pain at rest or on weight-bearing, and mid-thigh pain was reported by 1.4% of the patients after 5 years. The percentage of agreement between radiology assessment teams was 94 to 100%, except for distal line formation (48%). Radiographic evaluation showed stable stems and signs of excellent progressive proximal fixation and favourable bone remodeling. CONCLUSIONS: The excellent mid-term clinical and radiographic performances are in line with the design principles and coating properties of this new implant and earlier published results. TRIAL REGISTRATION: http://ClinicalTrials.gov , NCT03469687 . Registered 19 March 2018 - Retrospectively registered.

Tourniquet time in total knee arthroplasty.

BACKGROUND: Whether the arterial tourniquet in total knee arthroplasty (TKA) is a friend or a foe is still debated. Longer ischemia causes hypoxic damage; yet short duration of a tourniquet may influence outcome. Understanding the time-dependent influence of the tourniquet in TKA patients could improve the overall outcome and safety. The purpose of the study was to measure the tourniquet-induced time-dependent alterations in skeletal muscle metabolism in TKA to establish a 'safe tourniquet time.' METHODS: In the femoral quadriceps muscle of 12 patients undergoing a total knee arthroplasty with a tourniquet (TKA) we measured the ischemic response using microdialysis. Lactate, pyruvate, glucose and glycerol were measured in the muscle underneath the tourniquet, in the ischemic muscle distally to the tourniquet and in the opposite muscle as a reference. RESULTS: Lactate pyruvate ratio (L/P ratio) increased time-dependently after 15min of ischemia. L/P ratio increased faster underneath the tourniquet compared to ischemic tissue distal to the tourniquet. Glycerol was elevated underneath the tourniquet compared to ischemic tissue distal to the tourniquet and correlated to the individual ischemic response. Only minor increases in creatine-kinase, asparagine-aminotransferase, and lactate-dehydrogenase were observed. Thirty minutes of reperfusion normalized lactate levels. CONCLUSIONS: The muscle underneath the tourniquet suffered more from ischemia than the ischemic tissue distal to the tourniquet. Less than 15min of ischemia did not increase ischemic markers. If any muscle damage occurs from longer tourniquet time, it is likely reversible and occurs mainly underneath the tourniquet. Fifteen minutes of ischemia appears safe.