Data sharing across osteoarthritis research groups and disciplines: Opportunities and challenges.

Background: Osteoarthritis is a heterogeneous condition characterised by a wide variety of factors and represents a worldwide healthcare challenge. There are multiple clinical and research specialisms involved in the diagnosis, prognosis and treatment of osteoarthritis, and there may be opportunities to share or pool data which are currently not being utilised. However, there are challenges to doing so which require carefully structured solutions and partnership working. Methods: Interviews were conducted with nine experts from various fields within osteoarthritis research. A semi-structured approach was used, and thematic analysis applied to the results. Results: Generally, osteoarthritis researchers were supportive of data sharing, provided it is done responsibly and without impacting data integrity. Benefits identified included increasing typically low-powered data, the potential for machine learning opportunities, and the potential for improved patient outcomes. However, a number of challenges were identified, relating to: data security, data harmonisation, storage costs, ethical considerations and governance. Conclusions: There is clear support for increased data sharing and partnership working in osteoarthritis research. Further investigation will be required to navigate the complex issues identified; however, it is clear that collaborative opportunities should be better facilitated and there may be innovative ways to do this. It is also clear that nomenclature within different disciplines could be better streamlined, to improve existing opportunities to harmonise data.

Gait function improvements, using Cardiff Classifier, are related to patient-reported function and pain following hip arthroplasty.

Summarizing results of three-dimensional (3D) gait analysis into a comprehensive measure of overall gait function is valuable to discern to what extent gait function is affected, and later recovered after surgery and rehabilitation. This study aimed to investigate whether preoperative gait function, quantified and summarized using the Cardiff Classifier, can predict improvements in postoperative patient-reported activities of daily living, and overall gait function 1 year after total hip arthroplasty (THA). Secondly, to explore relationships between pre-to-post surgical change in gait function versus changes in patient-reported and performance-based function. Thirty-two patients scheduled for THA and 25 nonpathological individuals were included in this prospective cohort study. Patients were evaluated before THA and 1 year postoperatively using 3D gait analysis, patient-reported outcomes, and performance-based tests. Kinematic and kinetic gait parameters, derived from 3D gait analysis, were quantified using the Cardiff Classifier. Linear regressions investigated the predictive value of preoperative gait function on postoperative outcomes of function, and univariate correlations explored relationships between pre-to-post surgical changes in outcome measures. Preoperative gait function, by means of Cardiff Classifier, explained 35% and 30% of the total variance in change in patient-reported activities of daily living, and in gait function, respectively. Moderate-to-strong correlations were found between change in gait function and change in patient-reported function and pain, while no correlations were found between change in gait function and performance-based function. Clinical significance: Preoperative gait function predicts postsurgical function to a moderate degree, while improvements in gait function after surgery are more closely related to how patients perceive function than their maximal performance of functional tests.

High tibial osteotomy results in improved frontal plane knee moments, gait patterns and patient-reported outcomes.

PURPOSE: The purpose of this study was to quantify changes in knee loading in the three clinical planes, compensatory gait adaptations and patient-reported outcome measures (PROMS) resulting from opening wedge high tibial osteotomy (HTO). METHODS: Gait analysis was performed on 18 participants (19 knees) with medial osteoarthritis (OA) and varus alignment pre- and post-HTO, along with 18 controls, to calculate temporal, kinematic and kinetic measures. Oxford Knee Score, Knee Outcome Survey and visual analogue pain scores were collected. Paired and independent sample tests identified changes following surgery and deviations from controls. RESULTS: HTO restored frontal and transverse plane knee joint loading to that of the control group, while reductions remained in the sagittal plane. Elevated frontal plane trunk sway (p = 0.031) and reduced gait speed (p = 0.042), adopted as compensatory gait changes pre-HTO, were corrected by the surgery. PROMs significantly improved (p ≤ 0.002). Centre of pressure (COP) was lateralised relative to the knee post-HTO (p < 0.001). Energy absorbed in the sagittal plane significantly increased post-HTO (p = 0.007), whilst work done in the transverse plane reduced (p ≤ 0.008). Pre-operative gait deviations from the control group that were retained post-HTO included smaller sagittal (p = 0.003) knee range of motion during gait, greater stance duration (p = 0.008) and altered COP location (anterior to the knee) in early stance (p = 0.025). CONCLUSIONS: HTO surgery restored frontal and transverse plane knee loading to normal levels and improved PROMs. Gait adaptations known to reduce knee loading employed pre-HTO were not retained post-HTO. Some gait features were found to differ between post-HTO subjects and controls. LEVEL OF EVIDENCE: II.

Identifying non-specific low back pain clinical subgroups from sitting and standing repositioning posture tasks using a novel Cardiff Dempster-Shafer Theory Classifier.

BACKGROUND: Low back pain (LBP) classification systems are used to deliver targeted treatments matched to an individual profile, however, distinguishing between different subsets of LBP remains a clinical challenge. METHODS: A novel application of the Cardiff Dempster-Shafer Theory Classifier was employed to identify clinical subgroups of LBP on the basis of repositioning accuracy for subjects performing a sitting and standing posture task. 87 LBP subjects, clinically subclassified into flexion (n = 50), passive extension (n = 14), and active extension (n = 23) motor control impairment subgroups and 31 subjects with no LBP were recruited. Thoracic, lumbar and pelvic repositioning errors were quantified. The Classifier then transformed the error variables from each subject into a set of three belief values: (i) consistent with no LBP, (ii) consistent with LBP, (iii) indicating either LBP or no LBP. FINDINGS: In discriminating LBP from no LBP the Classifier accuracy was 96.61%. From no-LBP, subsets of flexion LBP, active extension and passive extension achieved 93.83, 98.15% and 97.62% accuracy, respectively. Classification accuracies of 96.8%, 87.7% and 70.27% were found when discriminating flexion from passive extension, flexion from active extension and active from passive extension subsets, respectively. Sitting lumbar error magnitude best discriminated LBP from no LBP (92.4% accuracy) and the flexion subset from no-LBP (90.1% accuracy). Standing lumbar error best discriminated active and passive extension from no LBP (94.4% and 95.2% accuracy, respectively). INTERPRETATION: Using repositioning accuracy, the Cardiff Dempster-Shafer Theory Classifier distinguishes between subsets of LBP and could assist decision making for targeted exercise in LBP management.

Comparison of gait, functional activities, and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: an exploratory case-control analysis.

OBJECTIVE: To examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA. METHODS: Participants with unilateral moderate knee OA (Kellgren-Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life-5 Dimensions). RESULTS: Eight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120-130 vs 100-110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes. CONCLUSION: Several objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials.

Which osteoarthritic gait features recover following total knee replacement surgery?

BACKGROUND: Gait analysis can be used to measure variations in joint function in patients with knee osteoarthritis (OA), and is useful when observing longitudinal biomechanical changes following Total Knee Replacement (TKR) surgery. The Cardiff Classifier is an objective classification tool applied previously to examine the extent of biomechanical recovery following TKR. In this study, it is further developed to reveal the salient features that contribute to recovery towards healthy function. METHODS: Gait analysis was performed on 30 patients before and after TKR surgery, and 30 healthy controls. Median TKR follow-up time was 13 months. The combined application of principal component analysis (PCA) and the Cardiff Classifier defined 18 biomechanical features that discriminated OA from healthy gait. Statistical analysis tested whether these features were affected by TKR surgery and, if so, whether they recovered to values found for the controls. RESULTS: The Cardiff Classifier successfully discriminated between OA and healthy gait in all 60 cases. Of the 18 discriminatory features, only six (33%) were significantly affected by surgery, including features in all three planes of the ground reaction force (p<0.001), ankle dorsiflexion moment (p<0.001), hip adduction moment (p = 0.003), and transverse hip angle (p = 0.007). All but two (89%) of these features remained significantly different to those of the control group after surgery. CONCLUSIONS: This approach was able to discriminate gait biomechanics associated with knee OA. The ground reaction force provided the strongest discriminatory features. Despite increased gait velocity and improvements in self-reported pain and function, which would normally be clinical indicators of recovery, the majority of features were not affected by TKR surgery. This TKR cohort retained pre-operative gait patterns; reduced sagittal hip and knee moments, decreased knee flexion, increased hip flexion, and reduced hip adduction. The changes that were associated with surgery were predominantly found at the ankle and hip, rather than at the knee.

Does Gait Retraining Have the Potential to Reduce Medial Compartmental Loading in Individuals With Knee Osteoarthritis While Not Adversely Affecting the Other Lower Limb Joints? A Systematic Review.

OBJECTIVES: To review the literature regarding gait retraining to reduce knee adduction moments and their effects on hip and ankle biomechanics. DATA SOURCES: Twelve academic databases were searched from inception to January 2019. Key words "walk*" OR "gait," "knee" OR "adduction moment," "osteoarthriti*" OR "arthriti*" OR "osteo arthriti*" OR "OA," and "hip" OR "ankle" were combined with conjunction "and" in all fields. STUDY SELECTION: Abstracts and full-text articles were assessed by 2 individuals against a predefined criterion. DATA SYNTHESIS: Of the 11 studies, sample sizes varied from 8-40 participants. Eight different gait retraining styles were evaluated: hip internal rotation, lateral trunk lean, toe-in, toe-out, increased step width, medial thrust, contralateral pelvic drop, and medial foot weight transfer. Using the Black and Downs tool, the methodological quality of the included studies was fair to moderate ranging between 12 of 25 to 18 of 28. Trunk lean and medial thrust produced the biggest reductions in first peak knee adduction moment. Studies lacked collective sagittal and frontal plane hip and ankle joint biomechanics. Generally, studies had a low sample size of healthy participants with no osteoarthritis and assessed gait retraining during 1 laboratory visit while not documenting the difficulty of the gait retraining style. CONCLUSIONS: Gait retraining techniques may reduce knee joint loading; however, the biomechanical effects to the pelvis, hip, and ankle is unknown, and there is a lack of understanding for the ease of application of the gait retraining styles.

Development of a methodology for the standardisation and improvement of 'Smartphone' photography of patterned bruises and other cutaneous injuries.

Human bite-mark analyses can play a prominent role in forensic case investigations, including those involving sexual assault. High-quality photographs routinely secure a link between a bite-mark and an individual's dentition. Access to around the clock forensic photography, however, is often limited, resulting in delay and/or missed opportunities to record valuable evidence. The emergence of Smartphone high-quality photographic technology now provides a previously unimagined opportunity to gather timely forensic photographic evidence. Problems can arise, however, due to the relatively poor quality of the photographs, as a result of many of those taking photographs having received little or no forensic photography training. This study compares unassisted photography with assisted photography, by a specifically developed camera application (App), to provide a standardised method for taking forensic photographs. An App, written in Java, was hosted on the Google Android Operating System, on a Samsung Galaxy SII Smartphone. Twenty-four volunteers participated in a study to photograph a pseudo bite-mark using three methods, (1) unassisted (as a control), (2) assisted by an ABFO No.2 right-angled photographic reference scale and (3) assisted by the App. The App, method (3), was shown to consistently outperform methods (1) and (2), demonstrating greater standardisation and precision (p<0.001). Analysis of the data showed the extent to which acquiring an accurate photograph depends on the image being orthogonal to the camera. It appears likely that the relatively inaccurate photographs acquired by methods (1) and (2), were as a result of deviation from the plane, orthogonal to the bite-mark. Therefore, the App was successful in ensuring that the camera was both orthogonal and at an appropriate distance, relative to the bite-mark. Thus, the App enhanced the abilities of non-experts to acquire more accurate photographs and created the potential to significantly improve the quality of forensic photographs.

Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia.

BACKGROUND: The major clinical feature of ataxia telangiectasia (A-T) is severe progressive neurodegeneration with onset in infancy. This classical A-T phenotype is caused by biallelic null mutations in the ATM gene, leading to the absence of ATM protein and increased cellular radiosensitivity. We report an unusual case of A-T in a 41-year-old mother, A-T210, who had very mild neurological symptoms despite complete loss of ATM protein. METHODS: A neurological examination was performed, cellular radiosensitivity was assessed, and the ATM gene was sequenced. Skin fibroblasts and a lymphoblastoid cell line (LCL) were assayed for ATM protein expression and kinase activity. RESULTS: Patient A-T210 showed mild chorea, dystonia, and gait ataxia, walked independently, and drove a car. LCL and skin fibroblasts were radiosensitive and did not express ATM protein. Two ATM-null mutations were identified. CONCLUSIONS: The severe neurodegeneration resulting from loss of ATM can be mitigated in some circumstances.

Ataxia telangiectasia mutated-deficient B-cell chronic lymphocytic leukemia occurs in pregerminal center cells and results in defective damage response and unrepaired chromosome damage.

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease involving more than one molecular mechanism that leads to the transformation of CD5(+) B cells at either the pregerminal or postgerminal center stage of differentiation. It was previously demonstrated that ataxia telangiectasia mutated (ATM) gene mutations can occur in B-CLL and cause a defect in the p53 pathway. Here the role of ATM mutations in the pathogenesis of B-CLL is addressed. Of 50 B-CLL tumors with fully analyzed ATM and TP53, 16 had ATM mutations. Six of 50 B-CLLs showed mutations in TP53 and the remaining 28 tumors had wild-type ATM or TP53. No tumor had both ATM and TP53 mutations. Remarkably, all 16 ATM mutant B-CLLs showed the absence of somatic variable region heavy chain hypermutation indicating a pregerminal center cell origin and a common pathogenesis for these tumors. Furthermore, in 5 of the 16 B-CLLs, ATM mutation preceded the transformation stage of differentiation. At the cellular level, ATM mutant tumors exhibited a deficient ATM-dependent p53 response to gamma irradiation, failure to up-regulate TRAIL-R2, a downstream target that links irradiation-induced p53 response with apoptosis, and an inability to repair induced chromosome breaks. Mantle cell lymphoma (MCL) is also of pregerminal center origin and ATM mutations are frequent in this malignancy. It is concluded that ATM is likely to play an important role at the pregerminal center stage and a model is proposed where loss of ATM function during B-cell ontogeny drives B-CLL tumorigenesis in pregerminal B cells by a dual defect in p53 damage response and repair of chromosome breaks.