Physiotherapy - Theses

Haematological cancers are diagnosed in 50 people per day in Australia and are the second most common cause of cancer-related death in Australia. Treatment for haematological cancer needs to be systemic and often includes chemotherapy, whole-body radiotherapy and/or bone marrow transplantation (BMT). Side-effects of treatment with BMT are multifactorial, associated with the underlying disease, the patient factors (for example comorbidities) and concomitant medications (for example steroids and immunosuppressants). An allogeneic BMT uses stem cells from a healthy donor and is generally higher-risk and higher intensity compared to autologous BMT which uses the patient’s own stem cells. Common symptoms associated with BMT include fatigue, reduced physical function, pain, weight loss, poor health-related quality of life (HRQoL), anxiety and depression. Exercise has potential to improve the physical and psychological burden of BMT, however is not part of routine care before, during or following BMT in many countries globally and particularly in Australia, and more research is required to facilitate this implementation. Study 1 of this thesis is a systematic review synthesising the evidence examining the effect of exercise on outcomes such as functional exercise capacity, HRQoL and healthcare resource usage among adults treated for haematological disease with BMT. This systematic review included 24 randomised controlled trials (RCTs) and 3 prospective non-randomised experimental trials with a total of 2432 participants; and 19 RCTs were included in the meta-analysis. Thirteen studies included only recipients of allogeneic BMT or published subgroup analyses of allogeneic BMT recipients; five studies included only recipients of autologous BMT, and ten studies included a mixed population of allogeneic or autologous BMT. Studies included in this systematic review were generally of poor to moderate methodological quality and there was too much heterogeneity among factors including population, intervention and outcomes to provide conclusions regarding ideal mode and timing of exercise. The Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the quality of evidence for each meta-analysis. The meta-analysis found moderate-quality evidence that exercise compared to control (no exercise) improves functional exercise capacity, fatigue and global HRQoL. There was low-quality evidence that exercise compared to control reduces hospital length of stay, improves strength and increases overall body weight. Most of the effects of exercise were more pronounced in allogeneic BMT although this evidence was generally rated low-quality. There were no between-group effects for bone marrow engraftment, physical activity, respiratory function, fat mass or lean body mass, anxiety and depression. No serious adverse events were associated with the exercise interventions. Study 2 of this thesis is a prospective cohort study which primarily aimed to explore the feasibility of ‘late-commencing’ group-based exercise following allogeneic BMT. The phrase ‘late-commencing’ is used as the intervention commenced following hospital discharge at 60-days post-transplant, which is ‘late’ in comparison to the intervention in the subsequent Study 3. In Study 2, forty-three consecutive adults planned for allogeneic BMT for haematological disease were recruited and conducted baseline outcome testing pre-transplant, then commenced a group-based exercise and education intervention at 60-days post-transplant. The consent rate pre-transplant was 93%, eligibility to commence the intervention post-transplant was 77% (n=33 from 43; due to death, cancellation of transplant, or being medically unwell), and a further 16% (n=7) declined to participate in the intervention. Of the n=26 who commenced the intervention, 81% (n=21) completed it with 81% adherence to the exercise sessions. This study observed significant decline in functional exercise capacity and HRQoL from pre- to 60-days post-transplant; followed by significant improvement in these outcomes from 60-days to completion of intervention. Whilst these results should be interpreted with caution, this significant decline in outcomes raised the question that perhaps intervention is required earlier in the continuum of allogeneic BMT. Thus, Study 3 of this thesis is a prospective cohort study which introduced an ‘early-commencing’ group-based exercise program, defined as ‘early’ as it commenced upon admission to hospital prior to allogeneic BMT, which is early in comparison to the intervention in the aforementioned Study 2. In Study 3, forty-two consecutive adults with haematological disease were recruited and had baseline outcome testing prior to allogeneic BMT, then commenced the group-based exercise intervention upon hospital admission, a median [IQR] of 5.5 [1-7] days prior to BMT. There was 100% consent rate; 83% (n=35) continued the inpatient intervention until hospital discharge and 95% (n=40) completed at least some aspects of final outcome testing at 60-days post-transplant. Fifty-one percent of participants attended the group-based intervention greater than or equal to 3 times per week, and 83% attended greater than or equal to 2 times per week. There were no adverse events associated with the intervention, and the intervention was deemed to be safe and feasible for participants to participate in group-based exercise greater than or equal to 2 times per week during hospitalisation. Except for emotional wellbeing which improved over time, all other outcomes significantly declined during acute hospitalisation and recovered slightly, though not significantly, following discharge. This persistent significant decline suggests there may be biological contributing factors such as transplant toxicities and/or effects from medications such as steroids. It was observed that participants who attended exercise sessions more frequently demonstrated lower signs of clinical frailty at baseline and higher functional exercise capacity at 60-days post BMT. These observations suggest that increased emphasis on pre-transplant assessment of factors such as frailty may aid in targeting exercise interventions at those who need it most. Furthermore, understanding factors that may impact adherence to exercise is important, hence a qualitative study was conducted concurrently. Study 4 of this thesis is a qualitative study which conducted individual semi-structured interviews with 35 participants of Study 2 and Study 3 to characterise experiences and views, including barriers and facilitators, of participation in a group-based exercise program during or after allogeneic BMT. Six major themes were identified including (1) motivation, (2) physical opportunity and (3) capability to exercise; (4) psychosocial effects of group-based exercise; (5) experienced impact of participation in exercise; and (6) intervention design considerations. Main barriers to exercise participation included symptom severity; fluctuating health status; and distance or difficult access to an exercise facility or equipment. Main facilitators included encouragement from healthcare staff; peer-support in a group-based setting; flexibility; education; and ability to measure change. The improvement in emotional wellbeing seen in Study 3, was echoed in participant views which noted that the psychological impact of group-based exercise should not be underestimated. Ultimately the study highlighted the importance of individual exercise preferences, and flexible interventions with consideration of physical and psychological capability, opportunity and motivation to sustain exercise behaviours following BMT. The findings of this thesis support the safety and feasibility of exercise in BMT, and with moderate to low confidence note that exercise improves physical and psychosocial health outcomes. The feasibility of group-based exercise has been established through this thesis, and this approach may have benefits to psychological wellbeing and may be more cost-effective than individual supervised exercise. To build towards implementation of exercise into routine clinical care for adults treated with BMT, large multi-centre, powered, well-designed RCTs are required to confirm efficacy. It is recommended that these RCTs include measurement of pre-transplant frailty, treatment toxicities and use of medications (steroids, immunosuppressants) to determine the influence of these factors on ability of exercise to maintain or improve physical outcomes such as exercise capacity. Future RCTs should be designed in partnership with key stakeholders including patients, caregivers, clinicians, policymakers and administrators to maximise adoption. These RCTs should consider adopting similar principles of intervention and outcome testing that have demonstrated efficacy in previous RCTs and consider group-based elements to maximise psychological wellbeing. Future RCTs should prioritise measurement of cost-effectiveness to ascertain sustainability of the intervention in the real-world context.

Children born preterm are at greater risk of motor impairment, including cerebral palsy (CP) and developmental coordination disorder, compared with children born at term. Despite the important role participation, including participation in physical activity (PA), plays in promoting motor development, very little is known about participation for children born preterm at preschool age. Participation includes two components: attendance and involvement. It is a complex phenomenon, influenced by environmental and personal factors, and is recognised as an important outcome for children with motor impairment. This thesis aims to better understand correlates of participation for preschool age children born preterm, as well as means of promoting participation for this group. Study one focused on correlates of participation. It compared community participation for preschool age children born at <30 weeks’ gestation (VP) and at term, and explored motor impairment and social risk as possible correlates of participation. Perceived environmental barriers and facilitators of community participation were also assessed. Children born VP participated less frequently in community activities compared with children born at term. Higher social risk was associated with poorer participation outcomes for children born VP but not term, while there was little evidence motor impairment was associated with community participation. Finally, parents of children born VP perceived greater environmental barriers to participation compared with parents of children born at term. Study two was a systematic review exploring the efficacy of movement-based interventions for preschool age children (3-6 years), with or at risk of motor impairment, including children born preterm (<37 weeks’ gestation). This review highlighted the scarcity of randomised controlled trials (RCTs) or quasi RCTs exploring movement-based interventions for this age group. Overall, movement-based interventions did not significantly improve body structure and function or activity outcomes, while the heterogeneity of intervention design and study quality made it difficult to establish definite conclusions. In particular, there were no studies that assessed participation as an outcome. Study three explored the feasibility and acceptability of a novel intervention known as Dance PREEMIE (a Dance PaRticipation intervention for Extremely prEterm children with Motor Impairment at prEschool age), which aimed to improve PA participation for preschool age children born extremely preterm (<28 weeks’ gestation) or extremely low birthweight (<1000g), with motor impairment. Children enrolled in Dance PREEMIE were allocated to a weekly community dance class (8 weeks duration) taught by dance teachers who received study-specific training. Dance PREEMIE was feasible to implement in Melbourne, Australia. Classes were well-attended and enjoyable for children, while dance teachers reported improved self-efficacy for teaching children with motor impairment after the training. Overall, Dance PREEMIE was acceptable to both parents of participating children and dance teachers. Findings from this thesis indicate that preschool age children born preterm have poorer participation outcomes compared with their term born peers, and present evidence on the feasibility and acceptability of Dance PREEMIE, a novel PA participation intervention.

Physiotherapy - Theses

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