The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma In Vivo Models Confers a Major Survival Advantage in a CD24-dependent Manner.

Neuroblastoma is the most common extracranial tumor, accounting for 15% of all childhood cancer-related deaths. The long-term survival of patients with high-risk tumors is less than 40%, and MYCN amplification is one of the most common indicators of poor outcomes. Zika virus (ZIKV) is a mosquito-borne flavivirus associated with mild constitutional symptoms outside the fetal period. Our published data showed that high-risk and recurrent neuroblastoma cells are permissive to ZIKV infection, resulting in cell type-specific lysis. In this study, we assessed the efficacy of ZIKV as an oncolytic treatment for high-risk neuroblastoma using in vivo tumor models. Utilizing both MYCN-amplified and non-amplified models, we demonstrated that the application of ZIKV had a rapid tumoricidal effect. This led to a nearly total loss of the tumor mass without evidence of recurrence, offering a robust survival advantage to the host. Detection of the viral NS1 protein within the tumors confirmed that a permissive infection preceded tissue necrosis. Despite robust titers within the tumor, viral shedding to the host was poor and diminished rapidly, correlating with no detectable side effects to the murine host. Assessments from both primary pretreatment and recurrent posttreatment isolates confirmed that permissive sensitivity to ZIKV killing was dependent on the expression of CD24, which was highly expressed in neuroblastomas and conferred a proliferative advantage to tumor growth. Exploiting this viral sensitivity to CD24 offers the possibility of its use as a prognostic target for a broad population of expressing cancers, many of which have shown resistance to current clinical therapies. SIGNIFICANCE: Sensitivity to the tumoricidal effect of ZIKV on high-risk neuroblastoma tumors is dependent on CD24 expression, offering a prognostic marker for this oncolytic therapy in an extensive array of CD24-expressing cancers.

Interactions of the anti-FcRn monoclonal antibody, rozanolixizumab, with Fcγ receptors and functional impact on immune cells in vitro.

Rozanolixizumab is a humanized anti-neonatal Fc receptor (FcRn) monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4) sub-class, currently in clinical development for the treatment of IgG autoantibody-driven diseases. This format is frequently used for therapeutic mAbs due to its intrinsic lower affinity for Fc gamma receptors (FcγR) and lack of C1q engagement. However, with growing evidence suggesting that no Fc-containing agent is truly "silent" in this respect, we explored the engagement of FcγRs and potential functional consequences with rozanolixizumab. In the study presented here, rozanolixizumab was shown to bind to FcγRs in both protein-protein and cell-based assays, and the kinetic data were broadly as expected based on published data for an IgG4 mAb. Rozanolixizumab was also able to mediate antibody bipolar bridging (ABB), a phenomenon that led to a reduction of labeled FcγRI from the surface of human macrophages in an FcRn-dependent manner. However, the presence of exogenous human IgG, even at low concentrations, was able to prevent both binding and ABB events. Furthermore, data from in vitro experiments using relevant human cell types that express both FcRn and FcγRI indicated no evidence for functional sequelae in relation to cellular activation events (e.g., intracellular signaling, cytokine production) upon either FcRn or FcγR binding of rozanolixizumab. These data raise important questions about whether therapeutic antagonistic mAbs like rozanolixizumab would necessarily engage FcγRs at doses typically administered to patients in the clinic, and hence challenge the relevance and interpretation of in vitro assays performed in the absence of competing IgG.

Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is caused by mutations in SMN1. SMN2 is a paralogous gene with a C•G-to-T•A transition in exon 7, which causes this exon to be skipped in most SMN2 transcripts, and results in low levels of the protein survival motor neuron (SMN). Here we show, in fibroblasts derived from patients with SMA and in a mouse model of SMA that, irrespective of the mutations in SMN1, adenosine base editors can be optimized to target the SMN2 exon-7 mutation or nearby regulatory elements to restore the normal expression of SMN. After optimizing and testing more than 100 guide RNAs and base editors, and leveraging Cas9 variants with high editing fidelity that are tolerant of different protospacer-adjacent motifs, we achieved the reversion of the exon-7 mutation via an A•T-to-G•C edit in up to 99% of fibroblasts, with concomitant increases in the levels of the SMN2 exon-7 transcript and of SMN. Targeting the SMN2 exon-7 mutation via base editing or other CRISPR-based methods may provide long-lasting outcomes to patients with SMA.

A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn-/-;SMN2 and intermediate Smn2B/- SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone's activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn-/-; SMN2 SMA and Smn+/-; SMN2 healthy mice, we identified molecular targets linked to prednisolone's ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone's potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.

Implementing an advanced physiotherapy outpatient triaging service as a model for improvement for patients recently discharged following surgical intervention for hip fracture.

Every year there are 1.3 million hip fractures globally; this is expected to rise to 6 million by 2050. Estimates of global cost is 1.75 million disability adjusted life years, and in established market economies, costs associated with hip fracture represent 1.4% of the total healthcare burden. New models of care will be required to meet this demand. Advance physiotherapy roles in elective arthroplasty across global settings have demonstrated benefit in safely reducing time burden on surgical teams and healthcare costs. The utility of similar roles in the care of hip fracture is unclear. This quality initiative (2020-2023) aimed to implement and evaluate a new model of care substituting a surgical registrar with an advanced physiotherapist in a post-discharge hip fracture clinic. Across many nonlinear, action/reflection cycles, a multi-disciplinary team engaged to operationalize key implementation strategies, mapped to the Expert Recommendations for Implementing Change (ERIC) project. Across the reporting period, 346 patients were seen by an advanced physiotherapist. Eighty-one patients seen by an advanced physiotherapist required informal discussion with the consultant surgeon. Fifteen patients required a formal consultant review. There were no patient complaints, critical incidents or other unintended consequences. The net surgical time realized over the three years was 110 hours.

Implementation of a primary care asthma management quality improvement programme across 68 general practice sites.

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p < 0.001) after the intervention. The odds ratio of reporting good asthma control following the intervention was 1.15 (95% CI 1.09-1.22), p < 0.0001. This asthma management programme produced modest but highly statistically significant improvements in asthma outcomes. Key lessons learnt from this small-scale implementation will enable the methodology to be improved to maximise benefit in a larger scale role out.

Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.

BACKGROUND: Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. METHODS: We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn-/-; SMN2 and the less severe Smn2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. We also used experimental models of denervation and muscle injury in pre-weaned wild-type (WT) animals and siRNA-mediated knockdown in C2C12 muscle cells to conduct additional mechanistic investigations. RESULTS: Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak-/-, and Fn14-/- mice revealed dysregulated myopathy, myogenesis, and glucose metabolism pathways as a common skeletal muscle feature, providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, administration of the TWEAK/Fn14 agonist Fc-TWEAK improved disease phenotypes in the two SMA mouse models. CONCLUSIONS: Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.

Application of the extended technology acceptance model to explore clinician likelihood to use robotics in rehabilitation.

PURPOSE: Evidence suggests that patients with upper limb impairment following a stroke do not receive recommended amounts of motor practice. Robotics provide a potential solution to address this gap, but clinical adoption is low. The aim of this study was to utilize the technology acceptance model as a framework to identify factors influencing clinician adoption of robotic devices into practice. MATERIALS AND METHOD: Mixed methods including survey data and focus group discussions with allied health clinicians whose primary caseload was rehabilitation of the neurologically impaired upper limb. Surveys based on the technology acceptance measure were completed pre/post exposure to and use of a robotic device. Focus groups discussions based on the theory of planned behaviour were conducted at the conclusion of the study. RESULTS: A total of 34 rehabilitation clinicians completed the surveys with pre-implementation data indicating that rehabilitation clinicians perceive robotic devices as complex to use, which influenced intention to use such devices in practice. The focus groups found that lack of experience and time to learn influenced confidence to implement robotic devices into practice. CONCLUSION: This study found that perceived usefulness and perceived ease of use of a robotic device in clinical rehabilitation can be improved through experience, training and embedded technological support. However, training and embedded support are not routinely offered, suggesting there is a discordance between current implementation and the learning needs of rehabilitation clinicians.IMPLICATIONS FOR REHABILITATIONPatients do not receive adequate amounts of upper limb motor practice following a stroke, and although robotic devices have the potential to address this gap, clinical adoption is low.The technology acceptance model identified that clinicians perceive robotic devices to be complex to use with current implementation efforts failing to consider their training needs.Implementation adoption of robotic devices in rehabilitation should be supported with adequate training and technological support if sustainable practice change is to be achieved.

Cognitive Health Worries, Reduced Physical Activity and Fewer Social Interactions Negatively Impact Psychological Wellbeing in Older Adults During the COVID-19 Pandemic.

The Coronavirus pandemic has significantly affected psychological wellbeing in older adults, with cases of depression, anxiety and loneliness rising in the general population. Cognitive health has also potentially been affected, as social isolation can lead to cognitive decline. Worrying about cognitive health can be damaging to psychological wellbeing and is especially relevant to explore in the context of the Coronavirus pandemic. The objective of the present study was to explore the associations between cognitive health worries and wellbeing, and to investigate whether physical activity and social contact can mitigate negative effects of the pandemic on psychological wellbeing. Older adults (N = 191) completed an online survey which included measures of cognitive health worries, depression, anxiety, loneliness, social isolation, fatigue, impact of the Coronavirus pandemic, quality of life, subjective vitality, and physical activity. Analyses indicated that cognitive health worries, lower levels of physical activity and smaller amounts of social interaction were associated with poorer psychological and physical wellbeing. Results showed that worrying about cognitive health is associated with poorer wellbeing, and so interventions are needed to encourage positive cognitive functioning in times of social isolation. Promoting physical activity and social interaction is also beneficial, as results show that exercise and social contact are linked with improved wellbeing.

Promoting clinical best practice in a user-centred design study of an upper limb rehabilitation robot.

PURPOSE: Despite their promise to increase therapy intensity in neurorehabilitation, robotic devices have not yet seen mainstream adoption. Whilst there are a number of contributing factors, it is obvious that the treating clinician should have a clear understanding of the objectives and limitations of robotic device use. This study sought to explore how devices can be developed to support a clinician in providing clinical best practice. METHODS AND MATERIALS: A user-centred design study of a robotic device was conducted, involving build-then-use iterations, where successive iterations are built based on feedback from the use cycle. This work reports results of an analysis of qualitative and quantitative data describing the use of the robotic device in the clinical sessions, and from a focus group with the treating clinicians. RESULTS AND CONCLUSIONS: The data indicated that use of the device did not result in patient goal-setting and may have resulted in poor movement quality. Therapists expected a higher level of autonomy from the robotic device, and this may have contributed to the above problems. These problems can and should be addressed through modification of both the study design and device to provide more explicit instructions to promote clinical best practice.IMPLICATIONS FOR REHABILITATIONEncouraging clinical best practice when using evaluating prototype devices within a clinical setting is important to ensure that best practice is maintained - and can be achieved through both study and device designSupport from device developers can significantly improve the confidence of therapists during the use of that device in rehabilitation, particularly with new or prototype devicesEnd effector-based robotic devices for rehabilitation show potential for a wide variety of patient presentations and capabilities.

The impact of COVID-19 restrictions on occupational balance: A mixed method study of the experience of Australian occupational therapists.

INTRODUCTION: COVID-19 has seen unprecedented changes to the daily occupational lives of citizens across the globe as a result social and physical restrictions. Frontline healthcare workers health and wellbeing have been impacted but what of occupational balance? The aim of this study was to investigate if there was a change in the occupational balance of occupational therapists working in a metropolitan hospital during a COVID-19 lockdown. METHODS: All occupational therapists working in a metropolitan hospital were invited to participate in an online survey. Occupational Balance was measured using the Occupational Balance Questionnaire-11 (OBQ11). Participants retrospectively rated their occupational balance before COVID-19 restrictions were in place and again rated their current status during the restrictions. Participants were also asked to comment on strategies used to help them during the COVID-19 restrictions. RESULTS: Forty-two occupational therapists completed the survey. The mean total score prior to the COVID-19 restrictions was 19.4 and during restrictions was 19.0 (Z = -0.4, p = 0.68). There was a significant decrease in having sufficient to do during the COVID-19 restrictions (Z = -3.6, p < 0.001). Satisfaction with how time was spent in rest, recovery and sleep significantly increased during the restrictions (Z = -3.3, p = 0.001). Strategies used included engaging in valued activities, finding alternate ways of doing and showing gratitude. CONCLUSION: Occupational balance of occupational therapists remained high and satisfaction in how time was spent improved during COVID-19 restrictions. Occupational therapists implemented their own theoretical approach of adaptation to cope with the COVID-19 restrictions.

Goal attainment scaling outcomes in general inpatient rehabilitation: association with functional independence and perceived goal importance and difficulty.

OBJECTIVE: To investigate the association of goal attainment scaling outcomes with change in the Func-tional Independence Measure, and the association between the perceived importance, difficulty and degree of achievement of individual goals in general inpatient rehabilitation. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 208 participants admitted to inpatient rehabilitation in a metropolitan tertiary referral hospital in Melbourne, Australia. METHODS: Participants determined the nature of the goals and their importance, and therapists determined the difficulty of the goals. The associations were investigated using median regression and random effect ordinal regression. RESULTS: An increase of each point in the goal attainment scaling score was associated with an adjusted median increase of 0.34 points (95% confidence interval (CI): 0.18-0.5, p < 0.001) in Functional Independence Measure change. More important goals of similar difficulty (very important vs a little important: adjusted common odds ratio (cOR) = 1.97, 95% CI: 1.01-3.83, p = 0.045) and less difficult goals of similar importance (moderately difficult vs a little difficult cOR = 0.59, 95% CI: 0.04-0.87, p = 0.007; very difficult vs a little difficult cOR = 0.59, 95% CI 0.37-0.94, p = 0.027) were better achieved. CONCLUSION: Rehabilitation progress measured using the goal attainment scaling method is associated with changes in functional outcomes. For goals with similar difficulty, those with higher importance were better achieved, while for goals with similar importance, less difficult goals were better achieved.

Evaluating Anti-CD32b F(ab) Conformation Using Molecular Dynamics and Small-Angle X-Ray Scattering.

Complementary strategies of small-angle x-ray scattering (SAXS) and crystallographic analysis are often used to determine atomistic three-dimensional models of macromolecules and their variability in solution. This combination of techniques is particularly valuable when applied to macromolecular complexes to detect changes within the individual binding partners. Here, we determine the x-ray crystallographic structure of a F(ab) fragment in complex with CD32b, the only inhibitory Fc-γ receptor in humans, and compare the structure of the F(ab) from the crystal complex to SAXS data for the F(ab) alone in solution. We investigate changes in F(ab) structure by predicting theoretical scattering profiles for atomistic structures extracted from molecular dynamics (MD) simulations of the F(ab) and assessing the agreement of these structures to our experimental SAXS data. Through principal component analysis, we are able to extract principal motions observed during the MD trajectory and evaluate the influence of these motions on the agreement of structures to the F(ab) SAXS data. Changes in the F(ab) elbow angle were found to be important to reach agreement with the experimental data; however, further discrepancies were apparent between our F(ab) structure from the crystal complex and SAXS data. By analyzing multiple MD structures observed in similar regions of the principal component analysis, we were able to pinpoint these discrepancies to a specific loop region in the F(ab) heavy chain. This method, therefore, not only allows determination of global changes but also allows identification of localized motions important for determining the agreement between atomistic structures and SAXS data. In this particular case, the findings allowed us to discount the hypothesis that structural changes were induced upon complex formation, a significant find informing the drug development process. The methodology described here is generally applicable to deconvolute global and local changes of macromolecular structures and is well suited to other systems.

Molecular evolution of fibropapilloma-associated herpesviruses infecting juvenile green and loggerhead sea turtles.

Chelonid Alphaherpesvirus 5 (ChHV5) has long been associated with fibropapillomatosis (FP) tumor disease in marine turtles. Presenting primarily in juvenile animals, FP results in fibromas of the skin, connective tissue, and internal organs, which may indirectly affect fitness by obstructing normal turtle processes. ChHV5 is near-universally present in tumorous tissues taken from affected animals, often at very high concentrations. However, there is also considerable asymptomatic carriage amongst healthy marine turtles, suggesting that asymptomatic hosts play an important role in disease ecology. Currently, there is a paucity of studies investigating variation in viral genetics between diseased and asymptomatic hosts, which could potentially explain why only some ChHV5 infections lead to tumor formation. Here, we generated a database containing DNA from over 400 tissue samples taken from green and loggerhead marine turtles, including multiple tissue types, a twenty year time span, and both diseased and asymptomatic animals. We used two molecular detection techniques, quantitative (q)PCR and nested PCR, to characterize the presence and genetic lineage of ChHV5 in each sample. We found that nested PCR across multiple loci out-performed qPCR and is a more powerful technique for determining infection status. Phylogenetic reconstruction of three viral loci from all ChHV5-positive samples indicated widespread panmixia of viral lineages, with samples taken across decades, species, disease states, and tissues all falling within the same evolutionary lineages. Haplotype networks produced similar results in that viral haplotypes were shared across species, tissue types and disease states with no evidence that viral lineages associated significantly with disease dynamics. Additionally, tests of selection on viral gene trees indicated signals of selection dividing major clades, though this selection did not divide sample categories. Based on these data, neither the presence of ChHV5 infection nor neutral genetic divergence between viral lineages infecting a juvenile marine turtle is sufficient to explain the development of FP within an individual.

Lessons learnt from a primary care asthma improvement project.

Asthma is a very common disease that can occur at any age. In the UK and in many other countries it is mainly managed in primary care. The published evidence suggests that the key to improving diagnosis and management lies in better training and education rather than in the discovery of new medications. An asthma improvement project managed through the British Lung Foundation is attempting to do this. The project has three pilot sites: two in England supported by the Department of Health and one in Scotland supported by the Scottish Government. If the project is successful it will be rolled out to other health areas within the UK. The results of this project are not yet available. This article highlights the challenges encountered in setting up the project and may well be applicable to other areas in the UK and to other countries where similar healthcare systems exist. The encountered challenges reflect the complex nature of healthcare systems and electronic data capture in primary care. We discuss the differences between general practices in their ability and willingness to support the project, the training and education of their staff on asthma management, governance issues in relation to information technology systems, and the quality of data capture. Virtually all the challenges have now been overcome, but discussing them should ensure that others become aware of them at an early stage should they wish to undertake similar projects in the future.

Interpreting "Mind-Cure": William James and the "chief task of the science of human nature".

The private papers of the philosopher-psychologist, William James, indicate that he frequented several mental healers during his life, undertaking 100-200 therapeutic sessions concerning a range of symptoms from angina to insomnia. The success of the mind-cure movement constituted for James both a corroboration, and an extension, of the new research into the subconscious self and the psychogenesis of disease. Epistemologically, the experiences of those converts to the "mind-cure religion" exemplified his conviction that positivistic scientific enquiry can only reveal only one part of a wider reality. Metaphysically their reports comprised a powerful body of support for the existence of a "higher consciousness," a supernatural world of some description. The positing of such a source of "supernormal" healing power was, for James, the best way to reconcile the accounts of those who had been regenerated, via their faith, despite having exhausted all natural reserves of energy and will.

The reliability of three visual perception tests used to assess adults.

Summary.-The reliability of three adult visual perceptual tests was investigated. Participants aged 20 years and older (N = 221; 49 adults with neurological impairment, 172 adults without) completed the Developmental Test of Visual Perception-Adolescent and Adult (DTVP-A), the Motor-Free Visual Perception Test-3 (MVPT-3), and the Test of Visual Perceptual Skills (non-motor) Third Edition (TVPS-3). Participants (n = 46) without neurological impairment completed these tests twice. Cronbach's alpha for the DTVP-A, MVPT-3, and TVPS-3 total scales were .86, .74, and .80 and test-retest correlations .51, .71, and .72, respectively.

Goal achievement in the six months after inpatient rehabilitation for stroke.

PURPOSE: The purpose of the project was to identify characteristics associated with successful re-integration into the community post-inpatient rehabilitation after stroke. A key issue was determining re-integration from the person's perspective, taking into account the person's preferred lifestyle choices. RESEARCH DESIGN: A prospective exploratory follow up study. PARTICIPANTS: A consecutive sample of 45 participants discharged from IP rehabilitation following stroke and 23 carers associated with the participants. MEASURES: Goal attainment scaling was utilised to determine successful community integration. Factors that may have contributed to goal achievement were measured prior to discharge and at 6 months post-discharge. Scales used include the Functional Independence Measure, Mini Mental test, the CES-D depression scale and a self-efficacy scale, Strategies Used by People to Promote Health. London Handicap Scale scores and Carer Strain Index were collected at 6 months. RESULTS: Twenty percent of participants achieved all their goals. Significant correlations were observed between goal achievement score and concurrent measures of physical function, depression and self efficacy at 6 months post-discharge. CONCLUSIONS: Stroke survivors who achieved their goals were less likely to be depressed, showed stronger self efficacy beliefs and more positive perceptions of their participation in everyday and community life.