Informed Consent: Research Staff's Perspectives and Practical Recommendations to Improve Research Staff-Participant Communication.

Informed consent (IC) is the process of communication between research staff and potential research participants. However, ensuring that participants clearly understand what research participation entails, raises significant challenges. The aim of this study is to provide insight into some communication barriers that research staff are confronted with and make practical recommendations to improve communication between research staff and participants. A qualitative research study using semi-structured interviews (n = 13) with research staff from Ghent University Hospital was conducted. Data were transcribed verbatim and coded thematically. Our results indicate that communication- and process-related factors affect the IC process. Emergent recommendations include communication training, more interactive information materials and the use of digital alternatives, increasing general knowledge about research participation and patient- and public involvement.

Assessing the Clinical Value of Objective and Patient-Reported Audiovestibular Outcome Measures in the Risk Estimation of Systemic Cobalt Toxicity for Patients With a Metal-on-Metal Hip Implant.

OBJECTIVES: Based on limited evidence from case reports and small cohort studies of metal-on-metal (MoM) hip implant patients with presumed systemic cobalt (Co) toxicity, and a few animal studies on Co-induced damage to the otovestibular system, it was hypothesised that Co exhibits an ototoxic potential alongside other systemic manifestations. Preliminary investigations from our research group in MoM patients confirmed this assumption for the auditory system, whereas no signs of Co-induced vestibular impairment were detected, and a clear dose-response relationship between the auditory function and the blood Co levels was lacking. Therefore, the current study aimed to extend and validate these findings in a larger sample of MoM patients and control subjects, to explore the potential clinical value of audiovestibular outcome measures in the risk estimation of systemic Co toxicity in this patient population. DESIGN: Fifty patients (32 to 68 years) with a primary unilateral/bilateral MoM hip implant were matched for age, gender, and noise exposure to 50 nonimplanted control subjects. Both groups underwent the same protocol, consisting of an objective auditory [i.e., conventional and high-frequency audiometry, transient-evoked and distortion (TEOAEs and DPOAEs), auditory brainstem responses] and vestibular (i.e., cervical and ocular vestibular evoked myogenic potentials, horizontal and vertical video head impulse tests) test battery, a questionnaire inquiring auditory, balance, and general neurological symptoms, and a blood sample collection to determine the plasma Co concentration. RESULTS: The auditory test battery presented consistently higher audiometric thresholds in the MoM patient group, with group differences ranging from 2.1 to 5.7 dB in the lower frequencies (0.25 to 6.0 kHz) and from 4.6 to 9.3 dB in the high frequencies (8.0 to 14.0 kHz). Group differences at high frequencies were statistically significant ( p ≤ 0.001). Additionally, significantly lower TEOAE ( p = 0.009) and DPOAE ( p < 0.001) amplitudes were observed in the MoM patients when the better ear was included in the analysis, and more absent TEOAE and DPOAE responses were found between 1.0 and 4.0 kHz (0.008 ≤ p ≤ 0.039). Within the vestibular test battery, the MoM patients showed longer N1 and P1 ocular vestibular evoked myogenic potentials latencies for the left ear, and lower video head impulse test gains for the left anterior and right posterior semicircular canals (0.005 ≤ p ≤0.035). The patient-reported (questionnaire) outcome delivered no significant group differences ( p > 0.01). Six patients had elevated Co levels according to our local institutional threshold (>4 or 5 µg/l for unilateral or bilateral MoM hip implants, resp.), but their audiovestibular outcome measures did not differ significantly from those of the other patients. CONCLUSIONS: Corresponding to our preliminary investigations, the results indicate possibly Co-induced (predominantly high-frequency) auditory impairment, probably triggered by toxic damage to the cochlear structures. However, the low mean difference values, the lack of group differences for the patient-reported outcome measures, and the lack of any relationship with the blood Co levels strongly reduce the clinical relevance of these findings. Therefore, the risk of Co-induced ototoxic impairment is considered to be clinically negligible for the majority of MoM hip implant patients, and the use of auditory tests in the risk estimation of systemic Co toxicity should be decided on a case-by-case basis.

Hip resurfacing arthroplasty in young patients: international high-volume centres' report on the outcome of 11,382 metal-on-metal hip resurfacing arthroplasties in patients ⩽50 years at surgery.

BACKGROUND: Total hip arthroplasty (THA) in patients younger than 50 years poses significant challenges including postoperative limitations of activity and higher failure rates. Sub-par outcomes of hip resurfacing arthroplasty (HRA) in registries remain controversial due to multiple confounders. Favourable HRA results in some studies are often regarded as irreproducible. The aim of this study is to analyse HRA outcomes in a large international cohort. PATIENTS AND METHODS: We compiled a database of 11,382 HRA patients ⩽50 years from an international group of 27 experienced HRA centres from 13 countries. 18 different metal-on-metal (MoM) HRA designs were included with a mean follow-up of 7.6 years. Outcomes were implant survivorship, revision rates, causes for revision, clinical scores and metal ion levels. Outcomes were compared between genders, sizes, implant types and pre-operative diagnoses. RESULTS: Overall cumulative Kaplan-Meier survivorship was 88.9% at 22 years (95% CI: 88.3-89.5%). 2 HRA designs (DePuy Articular Surface Replacement (ASR), and Corin Cormet Hip Resurfacing System (CORMET)) led to inferior results while all others yielded similar survivorships. Excluding ASR and CORMET, implant survivorship in 11,063 cases was 95% at 10 years and 90% at 22 years. In men, implant survivorship was excellent: 99% at 10 years and 92.5% at 21 years. In females, implant survivorship was 90% at 10 years and 81.3% at 22 years. The overall revision rate was 3.6% with most common reasons for revision being implant loosening and adverse local tissue reactions. The best survivorship was found in patients with osteoarthritis (95% CI, 92.1-93.3% at 22 years), the poorest was among dysplastic hips (78.3%; 95% CI, 76.5-80.1% at 20 years, p < 0.001). CONCLUSIONS: Comparable revision rates demonstrated here may mitigate some concerns for safety and longevity of MoM HRA implants. Higher demands for activity and functionality in younger patients make HRA a potential alternative to THA.

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO2) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 µg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 µg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 µg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program.

Special Issue "Novel Research about Biomechanics and Biomaterials Used in Hip, Knee and Related Joints".

Joint replacement is a very successful medical treatment [...].

The concept of justifiable healthcare and how big data can help us to achieve it.

Over the last decades, the face of health care has changed dramatically, with big improvements in what is technically feasible. However, there are indicators that the current approach to evaluating evidence in health care is not holistic and hence in the long run, health care will not be sustainable. New conceptual and normative frameworks for the evaluation of health care need to be developed and investigated. The current paper presents a novel framework of justifiable health care and explores how the use of artificial intelligence and big data can contribute to achieving the goals of this framework.

The ototoxic potential of cobalt from metal-on-metal hip implants: a pilot study on the patient-reported auditory, vestibular, and general neurological outcome.

OBJECTIVE: This study aimed to systematically investigate the ototoxic potential of cobalt in patients with a metal-on-metal (MoM) hip implant, using objective auditory and vestibular assessments and a questionnaire. The results of the objective evaluation were published previously, whereas the current study focused on the questionnaire outcome and its relationship to the blood cobalt level. Design and study sample: Twenty patients (33-65 years) with a primary MoM hip implant and 20 non-implanted control subjects, matched for age, gender, and noise exposure, received a questionnaire to evaluate the presence of several hearing and balance symptoms (part 1) and general neurological issues (part 2). RESULTS: Concerning part 1, the proportion of auditory-related symptoms in general (p = 0.022) and tinnitus (p = 0.047) was significantly higher in the MoM patient group, whereas no group difference was found for hyperacusis, increased listening effort, and decreased speech understanding. Concerning part 2, no significant group differences were detected. Within the MoM patient group, the questionnaire outcome was not significantly different between the low-exposure and high-exposure subgroups according to the blood Co level. CONCLUSIONS: In line with our previous study, these results potentially imply Co-induced impairment to the auditory system, despite the lack of a clear dose-response relationship.

Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. TRIAL DESIGN: This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study. PARTICIPANTS: Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO2/FiO2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways). INTERVENTION AND COMPARATOR: Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. MAIN OUTCOMES: The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO2/FiO2 ratio, P(A-a)O2 gradient and a/A PO2 ratio. (PAO2= Partial alveolar pressure of oxygen, PaO2=partial arterial pressure of oxygen, FiO2=Fraction of inspired oxygen). RANDOMISATION: Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm. TRIAL STATUS: ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on May 11th, 2020 (ClinicalTrials.gov Identifier: NCT04382755 ) and on EudraCT (Identifier: 2020-002130-33 ). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The Ototoxic Potential of Cobalt From Metal-on-Metal Hip Implants: Objective Auditory and Vestibular Outcome.

OBJECTIVES: During the past decade, the initial popularity of metal-on-metal (MoM) hip implants has shown a progressive decline due to increasingly reported implant failure and revision surgeries. Local as well as systemic toxic side effects have been associated with excessive metal ion release from implants, in which cobalt (Co) plays an important role. The rare condition of systemic cobaltism seems to manifest as a clinical syndrome with cardiac, endocrine, and neurological symptoms, including hearing loss, tinnitus, and imbalance. In most cases described in the literature, revision surgery and the subsequent drop in blood Co level led to (partial) alleviation of the symptoms, suggesting a causal relationship with Co exposure. Moreover, the ototoxic potential of Co has recently been demonstrated in animal experiments. Since its ototoxic potential in humans is merely based on anecdotal case reports, the current study aimed to prospectively and objectively examine the auditory and vestibular function in patients implanted with a MoM hip prosthesis. DESIGN: Twenty patients (15 males and 5 females, aged between 33 and 65 years) implanted with a primary MoM hip prosthesis were matched for age, gender, and noise exposure to 20 non-implanted control subjects. Each participant was subjected to an extensive auditory (conventional and high-frequency pure tone audiometry, transient evoked and distortion product otoacoustic emissions [TEOAEs and DPOAEs], auditory brainstem responses [ABR]) and vestibular test battery (cervical and ocular vestibular evoked myogenic potentials [cVEMPs and oVEMPs], rotatory test, caloric test, video head impulse test [vHIT]), supplemented with a blood sample collection to determine the plasma Co concentration. RESULTS: The median [interquartile range] plasma Co concentration was 1.40 [0.70, 6.30] µg/L in the MoM patient group and 0.19 [0.09, 0.34] µg/L in the control group. Within the auditory test battery, a clear trend was observed toward higher audiometric thresholds (11.2 to 16 kHz), lower DPOAE (between 4 and 8 kHz), and total TEOAE (1 to 4 kHz) amplitudes, and a higher interaural latency difference for wave V of the ABR in the patient versus control group (0.01 ≤ p < 0.05). Within the vestibular test battery, considerably longer cVEMP P1 latencies, higher oVEMP amplitudes (0.01 ≤ p < 0.05), and lower asymmetry ratio of the vHIT gain (p < 0.01) were found in the MoM patients. In the patient group, no suggestive association was observed between the plasma Co level and the auditory or vestibular outcome parameters. CONCLUSIONS: The auditory results seem to reflect signs of Co-induced damage to the hearing function in the high frequencies. This corresponds to previous findings on drug-induced ototoxicity and the recent animal experiments with Co, which identified the basal cochlear outer hair cells as primary targets and indicated that the cellular mechanisms underlying the toxicity might be similar. The vestibular outcomes of the current study are inconclusive and require further elaboration, especially with respect to animal studies. The lack of a clear dose-response relationship may question the clinical relevance of our results, but recent findings in MoM hip implant patients have confirmed that this relationship can be complicated by many patient-specific factors.

Development, validation and application of an inductively coupled plasma - mass spectrometry method to determine cobalt in metal-on-metal prosthesis patients using volumetric absorptive microsampling.

Metal-on-metal (MoM) prostheses, in which the bearing surfaces are made of a metal alloy, may release metal ions upon wear and corrosion, potentially inducing both local and systemic toxicity. As the systemic cobalt concentration increases with the degree of implant wear, this concentration needs to be monitored as a means of assessing implant function and the risk of adverse effects. Here, we report on the development, validation and application of a method to quantitatively assess these Co concentrations in whole blood, based on the combination of volumetric absorptive microsampling (VAMS) and inductively coupled plasma - mass spectrometry (ICP-MS). This method could allow patients to collect the required samples at home, as VAMS samples are easy to collect and can be transported to the laboratory via regular mail. The extraction procedure utilized an alkaline extraction mixture with yttrium as internal standard and proved to be independent of the hematocrit and age of the VAMS samples. The Co concentrations in the VAMS extracts were measured using quadrupole-based ICP-MS. The analytical method covers a range of 2-300 µg/L and displays excellent accuracy (bias ≤4%) and imprecision (relative standard deviation ≤ 5% and ≤15% at the lower limit of quantitation (LLOQ)). The method was applied to venous VAMS samples of MoM prosthesis patients (n = 78), yielding promising results. The comparison of these results with those obtained on the corresponding liquid whole blood samples, showed a correlation coefficient of 0.99 and 87% of the data fulfilled the criteria proposed by the Royal College of Pathologists of Australasia (RCPA).

Are TKA Kinematics During Closed Kinetic Chain Exercises Associated with Patient-reported Outcomes? A Preliminary Analysis.

BACKGROUND: Kinematic patterns after TKA can vary considerably from those of the native knee. It is unknown, however, if there is a relationship between a given kinematic pattern and patient satisfaction after TKA. QUESTIONS/PURPOSES: Is there an association between kinematic patterns as measured by AP translation during open kinetic chain flexion-extension and closed kinetic chain exercises (rising from a chair and squatting) and a custom aggregate of patient-reported outcome measures (PROMs) that targeted symptoms, pain, activities of daily living (ADL), sports, quality of life (QOL), and patient satisfaction after TKA? METHODS: Thirty patients who underwent TKA between 2014 and 2016 were tested at a minimum follow-up of 6 months. As three different implants were used, per implant the first 10 patients who presented themselves at the follow-up consultations and were able to bend the knee at least 90°, were recruited. Tibiofemoral kinematics during an open kinetic chain flexion-extension and closed kinetic chain exercises-rising from a chair and squatting-were analyzed using fluoroscopy. A two-step cluster analysis was performed, resulting in two clusters of patients who answered the Knee Injury and Osteoarthritis Outcome Score and the satisfaction subscore of the Knee Society Score questionnaires. Cluster 1 (CL1) consisted of patients with better (good-to-excellent) patient-reported outcome measures scores (high-PROMs cluster); Cluster 2 (CL2) consisted of patients with poorer scores (low-PROMs cluster). Tibiofemoral kinematics were compared between patients in these clusters by performing a Mann-Whitney U test with Bonferroni correction. RESULTS: Concerning open kinetic chain flexion-extension, there was no difference in kinematic patterns between the patients in the high-PROMs cluster and those in the low-PROMs cluster, with the numbers available. However, during the closed-chain kinetic exercises, medially, initial anterior translation (femur relative to tibia) was found in patients in Cluster 1 during early flexion, but in those in Cluster 2, translation was steeper and ran more anteriorly (CL1 -1.5 ± 7.3%; CL2 -8.5 ± 4.4%); mean difference 7.0% [95% CI 0.1 to 13.8]; p = 0.046). In midflexion, the femur did not translate anterior nor posterior in relation to the tibia, resulting in a stable medial compartment in Cluster 1, whereas Cluster 2 had already started translating posteriorly (CL1 -0.7 ± 3.5%; CL2 3.4 ± 3.6%; mean difference -4.1% [95% CI -7.0 to -1.2]; p = 0.008). There was no difference, with the numbers available, between the two clusters with respect to posterior translation in deep flexion. Laterally, there was small initial anterior translation in early flexion, followed by posterior translation in midflexion that continued in deep flexion. Patients in Cluster 1 demonstrated more pronounced posterior translation in deep flexion laterally than patients in Cluster 2 did (CL1 8.3 ± 5.2%; CL2 3.5 ± 4.5%); mean difference 4.9% [95% CI 0.6 to 9.1]; p = 0.026). CONCLUSIONS: This study of total knee kinematics suggests that during closed kinetic chain movements, patients with poor PROM scores after TKA experience more anterior translation on the medial side followed by a medial mid-flexion instability and less posterior translation on the lateral side in deep flexion than patients with good PROM scores. The relationship of kinematic variations with patient-reported outcomes including satisfaction must be further elaborated and translated into TKA design and position. Reproduction of optimal kinematic patterns during TKA could be instrumental in improving patient satisfaction after total knee replacement. Future expansion of the study group is needed to confirm these findings.Level of Evidence Level II, therapeutic study.

Radiographic evaluation of hip resurfacing: the role of x-rays in the diagnosis of a problematic resurfaced hip.

INTRODUCTION: Hip resurfacing (HRA) requires a new standardised radiographic evaluation protocol. Evaluation of acetabular components is similar to total hip arthroplasty (THA) but femoral components require different criteria. This study evaluates the efficacy of a new femoral zonal system for radiographic HRA assessment in identifying clinical problems. METHODS: A new proximal femoral zonal system divides implant-cement-bone interfaces at head and neck into 7 DeSmet zones. 611 in situ and 100 revised HRA were assessed for component positioning, borderline findings (reactive lines, cortical thickening, cancellous condensation) or sinister findings (lucent lines, bone resorption, osteolysis). Findings were correlated with gender, size, implant survival, clinical scores, metal ions, and adverse soft tissue reactions (ALTR). RESULTS: Radiological changes were found in 265 hips (37.3%), 154 sinister (21.7%) and 111 borderline (15.6%). 84% of revisions had sinister findings versus 11.4% of in situ HRA (p < 0.001). The mean number of abnormal acetabular and femoral zones was 3.3 in revised compared to 0.6 in situ HRA (p < 0.001). Sinister findings were associated with female gender, lower clinical scores, smaller sizes or ASR design (all: p < 0.001). Metal ions were higher with sinister (p < 0.001) and borderline (p < 0.01) findings compared to normal radiographs. Pathological findings in ⩾4 zones had a sensitivity of 50% and specificity of 94.2% (AUC = 0.898) in detecting hips with ALTR (odds ratio = 49). CONCLUSION: In order to accurately evaluate progressive radiographic changes in HRA, specific zones have been established around the femoral component. There was a high correlation between radiographic findings and outcome measures. 84% of problematic hips and 90.4% of proven ALTR had sinister changes.

An evaluation of the influence of force- and weight bearing (a)symmetry on patient reported outcomes after total knee arthroplasty.

It has been reported that balance impairments and asymmetrical movement patterns occur in patients after total kne arthroplasty (TKA). The purpose of this study was to evaluate if force- and weight-bearing asymmetry correlate with patient-reported outcomes (PROMs). Twenty patients were prospectively analysed up to 6 months after TKA. Quadriceps- and hamstring force were measured using a hand-held dynamometer. Vertical ground reaction forces during sit-to-stand, stair descending and squatting were assessed by force plates. Patients were asked to complete the KOOS, OKS and 2011 KSS. The symmetry-ratios during sit-to-stand, squat and stair-descent improved significantly. Preopera-tive quadriceps-force was positively correlated with KOOS-Symptoms (r=0.583, p=0.037). The pre-operative load-symmetry ratio during STS was negatively correlated with improvement in KOOS Pain (r=-0.675, p=0.011) and Symptoms (r=-0.674, p=0.008). In deep flexion, preoperative bodyweight ratio was positively correlated with postoperative OKS (r=0.601, p=0.039), KSS-Satisfaction (r=0.675, p=0.011) and improvement in KSS-Satisfaction (r=0.684, p=0.029). Weight bearing and force asymmetry do exist before TKA and take up to at least 6-months to fully recover. The more symmetry in muscle-force and weight-bearing is found preoperatively, the better the PROMs will be at 6 months after surgery.

The patient results and satisfaction of knee arthroplasty in a validated grading system.

INTRODUCTION: The validated Knee Osteoarthritis Grading System (KOGS) was implemented and clinical results were compared with patient satisfaction data and implant survivorship in a multi-centre study with surgeons familiar with unicompartmental knee arthroplasty (UKA), patellofemoral arthroplasty (PFA) and total knee arthroplasty (TKA). This is also the first study to evaluate the prevalence of UKA and TKA in consecutive osteoarthritis (OA) knee arthroplasties assessed by this system.. METHOD: A consecutive cohort of knees was gathered at three different institutions as categorized by KOGS and surgically treated with the recommended implant unless clinical reasons or patient preference precluded such an option. One thousand one hundred seventy-seven consecutive knees were evaluated including 311 TKA (26%), 695 medial UKA (59%), 154 lateral UKA (13%) and 17 PFA (2%) and the results of the categories evaluated with the Oxford Knee Score (OKS) and the complications reflected in the different categories. RESULTS: The failure rate of the UKA (3.5%) or TKA (1.6%) is not higher than accepted results in the literature and the difference in complications is negligible between the UKA (72%) and TKA (26%) cohorts. Revision of a UKA to a TKA as an endpoint was 0.58% with ipsilateral progression at 0.8% over a period of five to 84 months (mean follow-up of 36 months) despite the 'excessive' proportion of UKA in this cohort. The Oxford Score improvement is significant in TKA and UKA and contributes to the acceptable outcomes (The OKS for TKA improved from 20 pre-operatively to 36 post-operatively and the UKA improved from 22 pre-operatively to 39 post-operatively). CONCLUSION: KOGS achieves acceptable early survival and functional results when implemented and is a suitable tool for identifying the preferred implant as was validated.

Rationalized Development of a Campus-Wide Cell Line Dataset for Implementation in the Biobank LIMS System at Bioresource Center Ghent.

The Bioresource center Ghent is the central hospital-integrated biobank of Ghent University Hospital. Our mission is to facilitate translational biomedical research by collecting, storing and providing high quality biospecimens to researchers. Several of our biobank partners store large amounts of cell lines. As cell lines are highly important both in basic research and preclinical screening phases, good annotation, authentication, and quality of these cell lines is pivotal in translational biomedical science. A Biobank Information Management System (BIMS) was implemented as sample and data management system for human bodily material. The samples are annotated by the use of defined datasets, based on the BRISQ (Biospecimen Reporting for Improved Study Quality) and Minimum Information About Biobank data Sharing (MIABIS) guidelines completed with SPREC (Standard PREanalytical Coding) information. However, the defined dataset for human bodily material is not ideal to capture the specific cell line data. Therefore, we set out to develop a rationalized cell line dataset. Through comparison of different datasets of online cell banks (human, animal, and stem cell), we established an extended cell line dataset of 156 data fields that was further analyzed until a smaller dataset-the survey dataset of 54 data fields-was obtained. The survey dataset was spread throughout our campus to all cell line users to rationalize the fields of the dataset and their potential use. Analysis of the survey data revealed only small differences in preferences in data fields between human, animal, and stem cell lines. Hence, one essential dataset for human, animal and stem cell lines was compiled consisting of 33 data fields. The essential dataset was prepared for implementation in our BIMS system. Good Clinical Data Management Practices formed the basis of our decisions in the implementation phase. Known standards, reference lists and ontologies (such as ICD-10-CM, animal taxonomy, cell line ontology…) were considered. The semantics of the data fields were clearly defined, enhancing the data quality of the stored cell lines. Therefore, we created an essential cell line dataset with defined data fields, useable for multiple cell line users.

Biobank Quality Management in the BBMRI.be Network.

From as early as 2005, different guidelines and quality standards covering biobank activities and sample handling methods have been developed to improve and guarantee the reproducibility of biomarker research. Ten years on, the BBMRI.be Quality working group wanted to gauge the current situation of these aspects in the biobanks of the BBMRI.be network. To this end, two online surveys were launched (fall 2017 and fall 2018) to the biobank quality managers in the BBMRI.be network to determine the status and setup of their current quality management system (QMS) and how their QMS and related practices have evolved over a 14 month time period. All biobanks addressed by the two surveys provided a complete response (12 and 13, respectively). A QMS was implemented in 85% of biobanks, with 4 standards emerging as primary basis. Supplementary guidelines were used, with a strong preference for the ISBER best practices for biobanks. The Standard Preanalytical Code-an indicator of the preanalytical lifecycle of a biospecimen impacting the downstream analysis results-was already implemented in 50% of the biobanks while the other half intends future implementation. To assess and maintain the quality of their QMS, 62% of biobanks used self-assessment tools and 71% participated in proficiency testing schemes. The majority of biobanks had implemented procedures for general and biobank specific activities. However, policies regarding the business and sustainability aspect of biobank were only implemented in a limited number of biobanks. A clear desire for a peer-review audit was expressed by 69% of biobanks, with over half of them intending to implement the recently published biobank standard ISO20387. Overall, the biobanks of the BBMRI.be network have actively implemented a solid quality approach in their practices. The implementation of ISO 20387 may bring further professionalization of activities. Based on the needs expressed in this survey, the Quality working group will be setting up an audit program for the BBMRI.be biobanks, to enhance, harmonize and streamline their activities. On the whole, the biobanks in the BBMRI.be network are able to substantially contribute to translational research, as a primary facilitator guaranteeing high quality standards and reproducibility.

Correction: Meniscal Allograft Transplantation Does Not Prevent or Delay Progression of Knee Osteoarthritis.

[This corrects the article DOI: 10.1371/journal.pone.0156183.].

Detection of maturity and ligament injury using magic angle directional imaging.

PURPOSE: To investigate whether magnetic field-related anisotropies of collagen may be correlated with postmortem findings in animal models. METHODS: Optimized scan planning and new MRI data-processing methods were proposed and analyzed using Monte Carlo simulations. Six caprine and 10 canine knees were scanned at various orientations to the main magnetic field. Image intensities in segmented voxels were used to compute the orientation vectors of the collagen fibers. Vector field and tractography plots were computed. The Alignment Index was defined as a measure of orientation distribution. The knees were subsequently assessed by a specialist orthopedic veterinarian, who gave a pathological diagnosis after having dissected and photographed the joints. RESULTS: Using 50% less scans than reported previously can lead to robust calculation of fiber orientations in the presence of noise, with much higher accuracy. The 6 caprine knees were found to range from very immature (< 3 months) to very mature (> 3 years). Mature specimens exhibited significantly more aligned collagen fibers in their patella tendons compared with the immature ones. In 2 of the 10 canine knees scanned, partial cranial caudal ligament tears were identified from MRI and subsequently confirmed with encouragingly high consistency of tractography, Alignment Index, and dissection results. CONCLUSION: This method can be used to detect injury such as partial ligament tears, and to visualize maturity-related changes in the collagen structure of tendons. It can provide the basis for new, noninvasive diagnostic tools in combination with new scanner configurations that allow less-restricted field orientations.

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure.

BACKGROUND: Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications raise a number of urgent sociotechnical, ethical and legal questions, including optimal methods of data storage, management and access. Although the open science movement advocates unfettered access to research data, many of the UK's longitudinal cohort studies operate systems of managed data access, in which access is governed by legal and ethical agreements between stewards of research datasets and researchers wishing to make use of them. Amongst other things, these agreements aim to respect the reasonable expectations of the research participants who provided data and samples, as expressed in the consent process. Arguably, responsible data management and governance of data and sample use are foundational to the consent process in longitudinal studies and are an important source of trustworthiness in the eyes of those who contribute data to genomic and biosocial research. METHODS: This paper presents an ethnographic case study exploring the foundational principles of a governance infrastructure for Managing Ethico-social, Technical and Administrative issues in Data ACcess (METADAC), which are operationalised through a committee known as the METADAC Access Committee. METADAC governs access to phenotype, genotype and 'omic' data and samples from five UK longitudinal studies. FINDINGS: Using the example of METADAC, we argue that three key structural features are foundational for practising responsible data sharing: independence and transparency; interdisciplinarity; and participant-centric decision-making. We observe that the international research community is proactively working towards optimising the use of research data, integrating/linking these data with routine data generated by health and social care services and other administrative data services to improve the analysis, interpretation and utility of these data. The governance of these new complex data assemblages will require a range of expertise from across a number of domains and disciplines, including that of study participants. Human-mediated decision-making bodies will be central to ensuring achievable, reasoned and responsible decisions about the use of these data; the METADAC model described in this paper provides an example of how this could be realised.

Spine-hip relations in patients with hip osteoarthritis.

Patients with hip osteoarthritis often have an abnormal spine-hip relation (SHR), meaning the presence of a clinically deleterious spine-hip and/or hip-spine syndrome.Definition of the individual SHR is ideally done using the EOS® imaging system or, if not available, with conventional lumbopelvic lateral radiographs.By pre-operatively screening patients with abnormal SHR, it is possible to refine total hip replacement (THR) surgical planning, which may improve outcomes.An important component of the concept of kinematically aligned total hip arthroplasty (KA THA) consists of defining the optimal acetabular cup design and orientation based on the assessment of an individual's SHR, and use of the transverse acetabular ligament to adjust the cup positioning.The Bordeaux classification might advance the understanding of SHR and hopefully help improve THR outcomes. Cite this article: EFORT Open Rev 2018;3:39-44. DOI: 10.1302/2058-5241.3.170020.