Load bearing exercises and functional outcome of individuals with transfemoral amputation fitted with OPRA fixation

Individuals with lower limb amputation fitted with an OPRA osseointegrated fixation are facing an extensive rehabilitation program including static load bearing exercises (LBE). The application of a suitable amount of stress stimulates osseointegration and prepares the bone to tolerate the forces and moments that will be incurred during activities of daily living (ADL. At present, the monitoring is typically carried out using a normal bathroom weighing scale. This scale provides information only on the magnitude of the vertical component of the applied force. The moment around the long axis of the fixation when the femur is perpendicular to the ground is not assessed and neither are the components of force and moment generated on the other two axes.

Spatio-temporal characteristics of locomotion and functional outcomes of individuals with transfemoral amputation fitted with OPRA fixation

The conventional method of attachment of prosthesis involves a socket. A new method relying on osseointegrated fixation has emerged in the last decades. It has significant prosthetic benefits. Only a few studies demonstrated the biomechanical benefits. The ultimate aim of this study was to characterise the functional outcome of individuals with lower limb amputation fitted with osseointegrated fixation, which can be assess through temporal and spatial gait characteristics. The specific objective of this study was to present the key temporal and spatial gait characteristics of individuals with transfemoral amputation (TFA).

Hip joint stabilization vs. propulsion and resistance in individuals with transfemoral amputation

Joint moments and joint powers are widely used to determine the effects of rehabilitation programs and prosthetic components (e.g., alignments). A complementary analysis of the 3D angle between joint moment and joint angular velocity has been proposed to assess whether the joints are predominantly driven or stabilized.

Static load bearing exercises during rehabilitation of individuals with transfemoral amputation fitted with osseointegrated implant: Kinetic analysis

The desire to solve problems caused by socket prostheses in transfemoral amputees and the acquired success of osseointegration in the dental application has led to the introduction of osseointegration in the orthopedic surgery. Since its first introduction in 1990 in Gothenburg Sweden the osseointegrated (OI) orthopedic fixation has proven several benefits[1]. The surgery consists of two surgical procedures followed by a lengthy rehabilitation program. The rehabilitation program after an OI implant includes a specific training period with a short training prosthesis. Since mechanical loading is considered to be one of the key factors that influence bone mass and the osseointegration of bone-anchored implants, the rehabilitation program will also need to include some form of load bearing exercises (LBE). To date there are two frequently used commercially available human implants. We can find proof in the literature that load bearing exercises are performed by patients with both types of OI implants. We refer to two articles, a first one written by Dr. Aschoff and all and published in 2010 in the Journal of Bone and Joint Surgery.[2] The second one presented by Hagberg et al in 2009 gives a very thorough description of the rehabilitation program of TFA fitted with an OPRA implant. The progression of the load however is determined individually according to the residual skeleton’s quality, pain level and body weight of the participant.[1] Patients are using a classical bathroom weighing scale to control the load on the implant during the course of their rehabilitation. The bathroom scale is an affordable and easy-to-use device but it has some important shortcomings. The scale provides instantaneous feedback to the patient only on the magnitude of the vertical component of the applied force. The forces and moments applied along and around the three axes of the implant are unknown. Although there are different ways to assess the load on the implant for instance through inverse dynamics in a motion analysis laboratory [3-6] this assessment is challenging. A recent proof- of-concept study by Frossard et al (2009) showed that the shortcomings of the weighing scale can be overcome by a portable kinetic system based on a commercial transducer[7].

Walking ability of individuals with transfemoral amputation fitted with osseointegrated implant

The prosthetic benefits of osseointegrated fixation for individuals with limb loss, particularly those with transfemoral amputation (TFA), have been clearly demonstrated in the literature. However, very little information is currently available to established how this prosthetic benefits are translated into functional outcomes and, more precisely, walking abilities [1-3]. The ultimate aim of this presentation was to explore how walking abilities of a TFA fitted with an OPRA fixation could be assess through typical temporal and spatial gait characteristics[2].

Static load bearing exercises of individuals with transfemoral amputation fitted with an osseointegrated implant: Reliability of kinetic data

This study aimed at presenting the intra-tester reliability of the static load bearing exercises (LBEs) performed by individuals with transfemoral amputation (TFA) fitted with an osseointegrated implant to stimulate the bone remodelling process. There is a need for a better understanding of the implementation of these exercises particularly the reliability. The intra-tester reliability is discussed with a particular emphasis on inter-load prescribed, inter-axis and inter-component reliabilities as well as the effect of body weight normalisation. Eleven unilateral TFAs fitted with an OPRA implant performed five trials in four loading conditions. The forces and moments on the three axes of the implant were measured directly with an instrumented pylon including a six-channel transducer. Reliability of loading variables was assessed using intraclass correlation coefficients (ICCs) and percentage standard error of measurement values (%SEMs). The ICCs of all variables were above 0.9 and the %SEM values ranged between 0 and 87%. This study showed a high between-participants’ variance highlighting the lack of loading consistency typical of symptomatic population as well as a high reliability between the loading sessions indicating a plausible correct repetition of the LBE by the participants. However, these outcomes must be understood within the framework of the proposed experimental protocol.

One step closer into the design of fall protective device for individuals fitted with a bone-anchored prosthesis

The consequences of falls are often dreadful for individuals with lower limb amputation using bone-anchored prosthesis.[1-5] Typically, the impact on the fixation is responsible for bending the intercutaneous piece that could lead to a complete breakage over time. .[3, 5-8] The surgical replacement of this piece is possible but complex and expensive. Clearly, there is a need for solid data enabling an evidence-based design of protective devices limiting impact forces and torsion applied during a fall. The impact on the fixation during an actual fall is obviously difficult to record during a scientific experiment.[6, 8-13] Consequently, Schwartze and colleagues opted for one of the next best options science has to offer: simulation with an able-bodied participant. They recorded body movements and knee impacts on the floor while mimicking several plausible falling scenarios. Then, they calculated the forces and moments that would be applied at four levels along the femur corresponding to amputation heights.[6, 8-11, 14-25] The overall forces applied during the falls were similar regardless of the amputation height indicating that the impact forces were simply translated along the femur. As expected, they showed that overall moments generally increased with amputation height due to changes in lever arm. This work demonstrates that devices preventing only against force overload do not require considering amputation height while those protecting against bending moments should. Another significant contribution is to provide, for the time, the magnitude of the impact load during different falls. This loading range is crucial to the overall design and, more precisely, the triggering threshold of protective devices. Unfortunately, the analysis of only a single able-bodied participant replicating falls limits greatly the generalisation of the findings. Nonetheless, this case study is an important milestone contributing to a better understanding of load impact during a fall. This new knowledge will improve the treatment, the safe ambulation and, ultimately, the quality of life of individuals fitted with bone-anchored prosthesis.

Safety of OPRA procedure for individuals with upper limb amputation

Surgical implantations of osseointegrated fixations for bone-anchored prosthesis are developing at an unprecedented pace worldwide while initial skepticism in the orthopedic community is slowly fading away. Clearly, this option is becoming accessible to a wide range of individuals with limb loss. [1-18] The team led by Dr Rickard Branemark has previously published a number of landmark articles focusing on the benefits and safety of the OPRA fixation mainly for individual with lower limb loss, particularly those with transfemoral amputation. [1-3, 19-32] However, similar information is lacking for those with upper limb amputation. This team is once again taking a leading role by sharing a retrospective study focusing on the implant survival, adverse events, implant stability, and bone remodelling for 18 individuals with transhumeral amputation over a 5-year post-operative period. Therefore, a comprehensive analysis of the safety of the procedure is accessible for the first time. In essence, the results showed an implant survival rate of 83% and 80% at 2 and 5 year follow ups, respectively. The most frequent adverse events were superficial skin infections that occurred for 28% (5) participants while the least frequent was deep bone infection that happened only once. More importantly, 38% of complications due to infections were effectively managed with nonoperative treatments (e.g., revision of skin penetration site, local cleaning, antibiotics, restriction of soft tissue mobility). Implant stability and bone remodelling were satisfactory. Clearly, this study provided better understanding of the safety of the OPRA surgical and rehabilitation procedure for individuals with upper limb amputation while establishing standards and benchmark data for future studies. However, strong evidences of the benefits are yet to be demonstrated. However, increase in health related quality of life and functional outcomes (e.g., range of movement) are likely. Altogether, the team of authors are providing further evidence that bone-anchored attachment is definitely a promising alternative to socket prostheses.

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (​HFE, ​SLC40A1, ​TF, ​TFR2, ​TFRC, ​TMPRSS6) and others novel (​ABO, ​ARNTL, ​FADS2, ​NAT2, ​TEX14). SNPs at ​ARNTL, ​TF, and ​TFR2 affect iron markers in ​HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

The impact of neuropsychological functioning and coping style on perceived stress in individuals with first-episode psychosis and healthy controls

Stress is implicated in the development and course of psychotic illness, but the factors that influence stress levels are not well understood. The aim of this study was to examine the impact of neuropsychological functioning and coping styles on perceived stress in people with first-episode psychosis (FEP) and healthy controls (HC). Thirty-four minimally treated FEP patients from the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, and 26 HC participants from a similar demographic area participated in the study. Participants completed a comprehensive neuropsychological test battery as well as the Coping Inventory for Stressful Situations (task-, emotion- and avoidance-focussed coping styles) and Perceived Stress Scale (PSS). Linear regressions were used to determine the contribution of neuropsychological functioning and coping style to perceived stress in the two groups. In the FEP group, higher levels of emotion-focussed and lower levels of task-focussed coping were associated with elevated stress. Higher premorbid IQ and working memory were also associated with higher subjective stress. In the HC group, higher levels of emotion-focussed coping, and contrary to the FEP group, lower premorbid IQ, working memory and executive functioning, were associated with increased stress. Lower intellectual functioning may provide some protection against perceived stress in FEP.

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis

Background We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. Methods Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. Results Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (−6%; p = .032). Conclusions The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

The optimal frequency of aquatic physiotherapy for individuals with chronic musculoskeletal pain: a randomised controlled trial

Purpose: To establish whether there was a difference in health-related quality of life (HRQoL) in people with chronic musculoskeletal disorders (PwCMSKD) after participating in a multimodal physiotherapy program (MPP) either two or three sessions a week. Methods: Total of 114 PwCMSKD participated in this prospective randomised controlled trial. An individualised MPP, consisting of exercises for mobility, motor-control, muscle strengthening, cardiovascular training, and health education, was implemented either twice a week (G2: n = 58) or three times a week) (G3: n = 56) for 1 year. Outcomes: HRQoL physical and mental health state (PHS/MHS), Roland Morris disability Questionnaire (RMQ), Neck-Disability-Index (NDI) and Western Ontario and McMaster Universities’ Arthritis Index (WOMAC) were used to measure outcomes of MPP for people with chronic low back pain, chronic neck pain and osteoarthritis, respectively. Measures were taken at baseline, 8 weeks (8 w), 6 months (6 m), and 1 year (1 y) after starting the programme. Results: No statistically significant differences were found between the two groups (G2 and G3), except in NDI at 8 w (−3.34, (CI 95%: −6.94/0.84, p = 0.025 (scale 0–50)). All variables showed improvement reaching the following values (from baseline to 1 y) G2: PHS: 57.72 (baseline: 41.17; (improvement: 16.55%), MHS: 74.51 (baseline: 47.46, 27.05%), HRQoL 0.90 (baseline: 0.72, 18%)), HRQoL-VAS 84.29 (baseline: 58.04, 26.25%), RMQ 4.15 (baseline: 7.85, 15.42%), NDI 3.96 (baseline: 21.87, 35.82%), WOMAC 7.17 (baseline: 25.51, 19.10%). G3: PHS: 58.64 (baseline: 39.75, 18.89%), MHS: 75.50 (baseline: 45.45, (30.05%), HRQoL 0.67 (baseline: 0.88, 21%), HRQoL-VAS 86.91 (baseline: 52.64, 34.27%), RMQ 4.83 (baseline: 8.93, 17.08%), NDI 4.91 (baseline: 23.82, 37.82%), WOMAC 6.35 (baseline: 15.30, 9.32%). Conclusions: No significant differences between the two groups were found in the outcomes of a MPP except in the NDI at 8 weeks, but both groups improved in all variables during the course of 1 year under study.

IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection

Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases. The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset. A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.

Rehabilitation of individuals with bone-anchored prosthesis: State-of-the-art and challenges

Individuals with limb amputation fitted with conventional socket-suspended prostheses often experience socket-related discomfort leading to a significant decrease in quality of life. Bone-anchored prostheses are increasingly acknowledged as viable alternative method of attachment of artificial limb. In this case, the prosthesis is attached directly to the residual skeleton through a percutaneous fixation. To date, a few osseointegration fixations are commercially available. Several devices are at different stages of development particularly in Europe and the US.[1-15] Clearly, surgical procedures are currently blooming worldwide. Indeed, Australia and Queensland in particular have one of the fastest growing populations. Previous studies involving either screw-type implants or press-fit fixations for bone-anchorage have focused on fragmented biomechanics aspects as well as the clinical benefits and safety of the procedure. However, very few publications have synthetized this information and provided an overview of the current developments in bone-anchored prostheses worldwide, let alone in Australia. The purposes of the presentation will be: 1. To provide an overview of the state-of-art developments in bone-anchored prostheses with as strong emphasis on the design of fixations, treatment, benefits, risks as well as future opportunities and challenges, 2. To present the current international developments of procedures for bone-anchored prostheses in terms of numbers of centers, number of cases and typical case-mix, 3. To highlight the current role Australia is playing as a leader worldwide in terms of growing population, broadest range of case-mix, choices of fixations, development of reimbursement schemes, unique clinical outcome registry for evidence-based practice, cutting-edge research, consumer demand and general public interest.