Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

<p>Effekter av utvidet slagbehandling og samarbeid på tvers av forvaltningsnivå.</p><p>Hjerneslag er en av de hyppigste årsaker til alvorlig funksjonshemming og død i Norge, i tillegg at sykdommen medfører betydelige samfunnsmessige kostnader. Forekomsten er ca. 14 000 hjerneslag pr. år, og antallet forventes å øke betraktelig i årene fremover da antall eldre over 65 år vil øke sterkt.</p><p>Det er en stor utfordring å organisere helsetjenesten slik at behandlingstilbudet for denne pasientgruppen blir best mulig. Akuttbehandling i slagenhet er i dag det best dokumenterte behandlingstiltak, men effekten av videre rehabilitering og oppfølging har vært et lite prioritert område for forskning.</p><p>Hovedhensikten med denne avhandlingen har vært å framskaffe mer kunnskap om hva som kan oppnås for slagpasienter ved en systematisk organisering og samarbeid mellom sykehus og primærhelsetjeneste når det gjelder behandling og rehabilitering etter akuttbehandling i slagenhet. Studien som ligger til grunn for avhandlingen ble gjennomført ved Seksjon for hjerneslag, Medisinsk avdeling, St. Olavs Hospital i perioden 1995-1998.</p><p>Intervensjonen var å konstruere en ny behandlingskjede for slagpasienter hvor fokus på bedre samarbeid med primærhelsetjenesten, oppfølging av et ambulerende team, tidlig utreise fra sykehus og rehabilitering med utgangspunkt i hjemmet ble sterkt vektlagt. Den konstruerte behandlingskjeden ble evaluert med tanke på helsegevinst for den enkelte og bedre ressursutnytting sammenlignet med det tradisjonelle behandlingstilbudet.</p><p>Studien ble gjennomført som en klinisk randomisert kontrollert studie der 320 pasienter med akutt hjerneslag ble inkludert. 160 pasienter fikk ordinær slagenhet behandling med videre institusjonsrehabilitering og/eller oppfølging av primærhelsetjenesten, mens de øvrige 160 pasienter fikk oppfølging av et ambulerende team i henhold til den nye og konstruerte behandlingskjeden.</p><p>I de fire arbeidene som inngår i avhandlingen er det sett på risiko for alvorlig funksjonshemning og død, endring i funksjonsnivå og livskvalitet, samt kostnadsanalyser og ressursforbruk av helsetjenester. Pasientene i de to gruppene ble undersøkt og sammenlignet 6 og 12 måneder etter sykdomsdebut.</p><p>Resultatene av studien viste at sammenlignet med tradisjonell behandling oppnådde pasientene i intervensjonsgruppen signifikant bedre funksjonsnivå (p=0.017) og redusert risiko for alvorlig funksjonshemning og død (p=0.044) etter ett år. De viste også tendens til bedret livskvalitet samtidig som initial liggetid i institusjon ble redusert med 40 % (p=0.032). Det var ingen økning i totalt ressursforbruk eller kostnader i intervensjonsgruppen.</p><p>Oppsummert viser avhandlingen at en slagbehandlingskjede med fokus på samarbeid på tvers av forvaltningsnivå, oppfølging av et ambulerende team og rehabilitering mens pasientene bor hjemme gir meget positiv effekt.</p><p>Den kliniske betydning av disse resultater er at en oppfølging i form av en slagbehandlingskjede i tillegg til akutt behandling i slagenhet bør inngå som en integrert del av behandlingstilbudet for denne pasientgruppen.</p><p>Arbeidene er utført ved INM og ISM, Det medisinske fakultet, NTNU. 1.amanuensis, dr.med Bent Indredavik har vært hovedveileder og Professor dr.med Roar Johnsen biveileder.</p> / <p>Extended Stroke Unit Service and Early Supported Discharge. Short and Long-term Effects.</p><p><i>Background and purpose</i></p><p>Stroke imposes a considerable burden for patients, their caregivers and the society worldwide. It is a challenge to organise the healthcare service that can provide effective management of patients who have suffered from stroke. Several trials have shown that stroke unit care improves the outcome for stroke patients. More limited information exists about the most effective way to organise the follow-up care after the acute care in a stroke unit. Stroke patients conventionally receive a substantial part of their rehabilitation in hospital or in other institutions that offer 24 hours-stay.</p><p>The primary aim of this thesis was to increase knowledge about the organising of follow-up care for stroke patients after the acute care in a stroke unit. To achieve this we performed a trial to evaluate the short and long-term effects of an extended stroke unit service (ESUS), with early supported discharge from hospital, co-operation with the primary health care, and more emphasize on rehabilitation at home as essential elements.</p><p><i>Methods</i></p><p>We performed a randomized controlled trial in which 320 acute stroke patients admitted to the Stroke Unit at St. Olavs Hospital, Trondheim University Hospital were included and allocated either to ordinary stroke unit care (OSUS) (160 patients) with further in-patient rehabilitation or follow-up from the primary healthcare service, or to stroke unit care with early supported discharge (160 patients). The ESUS consisted of a mobile team which co-ordinate early supported discharge and further rehabilitation.</p><p>Included in this thesis are 4 papers based on data from this study population of acute stroke patients followed in one year after the onset of stroke. We wanted to compare the groups in relation to independency, quality of life (QoL) and resource use and costs.</p><p>• Functional outcome were measured as the proportion of patients who were independent as assessed by modified Rankin Scale (RS)(RS<2 =global independence) and Barthel Index (BI)(BI>95 = independent in ADL) at 26 weeks and 52 weeks, the differences in final residence and analyses to identify patients who benefited most of an early supported discharge service (paper I and II). All assessments were blinded.</p><p>• The outcome of QoL was measured by the Nottingham Health Profile (NHP) at 52 weeks. Other outcomes measured at 52 weeks were differences between the groups according to social activity, depression, cognitive function and the burden for carers’. (paper III).</p><p>• The use of all health services during the first 52 weeks was recorded prospectively in both groups; its costs were measured as service costs and represent a combination of calculated average costs and tariffs. Hospital expenses were measured as costs per inpatient day. The secondary objectives were to explore differences in costs between the groups with respect to different types of services, time of service delivery and stroke severity (paper IV).</p><p><i>Results</i></p><p>• Extended stroke unit service with early supported discharge and co-ordination by a mobile team improves functional outcome 6 months and 12 months after stroke. The Odds Ratio for independence at one year was 1.56 (95% C.I, 1.01-to 2.44). It was most beneficial for patients with moderate stroke (papers I and II).</p><p>• Extended stroke unit service with early supported discharge can improve long-term quality of life measured by global NHP. The ESUS group had a significant better QoL after one year than the OSUS group (p = 0.048). There were no significant differences between the groups in the secondary outcomes social activity, depression and cognitive function. The caregivers who got their patients early at home did not report an increased burden compared to caregivers whose patients became ordinary stroke unit care (paper III).</p><p>• The length of initial institutional stay (hospital and rehab.clinic) were reduced with 40 % for the patients offered extended stroke unit service (18.6 days in the ESUS versus 31.1 days in the OSUS) (p=0.032). There was also a reduction in average number of total inpatient days during the first year in favour of the ESD group (p = 0.012) (paper IV).</p><p>• The total health services costs for ESUS was equal or less than costs for ordinary care during the first year after stroke. There was a non-significant reduction in total mean service costs in the ESUS group (EUR 18937 / EUR 21824). The service seemed to be most cost effective for patients with moderate severity of stroke (23% lower mean costs compared to OSUS). The important cost savings caused by reduced length of institutional stay did not lead to an increase in costs for home-based rehabilitation (paper IV).</p><p><i>Conclusion</i></p><p>An extended stroke unit service with early supported discharge improved functional outcome and reduced the length of stay in institutions compared to traditional stroke unit care. It also seems that this service can improve long-term quality of life. The costs are equal or less than costs for ordinary care.</p><p>An early, well organised discharge from hospital co-ordinated by a mobile team seems to be an important contribution in the treatment of stroke patients and should be considered, in addition to organised in-patient stroke unit care, as a part of a comprehensive stroke care.</p>

Effekter av utvidet slagbehandling og samarbeid på tvers av forvaltningsnivå. Hjerneslag er en av de hyppigste årsaker til alvorlig funksjonshemming og død i Norge, i tillegg at sykdommen medfører betydelige samfunnsmessige kostnader. Forekomsten er ca. 14 000 hjerneslag pr. år, og antallet forventes å øke betraktelig i årene fremover da antall eldre over 65 år vil øke sterkt. Det er en stor utfordring å organisere helsetjenesten slik at behandlingstilbudet for denne pasientgruppen blir best mulig. Akuttbehandling i slagenhet er i dag det best dokumenterte behandlingstiltak, men effekten av videre rehabilitering og oppfølging har vært et lite prioritert område for forskning. Hovedhensikten med denne avhandlingen har vært å framskaffe mer kunnskap om hva som kan oppnås for slagpasienter ved en systematisk organisering og samarbeid mellom sykehus og primærhelsetjeneste når det gjelder behandling og rehabilitering etter akuttbehandling i slagenhet. Studien som ligger til grunn for avhandlingen ble gjennomført ved Seksjon for hjerneslag, Medisinsk avdeling, St. Olavs Hospital i perioden 1995-1998. Intervensjonen var å konstruere en ny behandlingskjede for slagpasienter hvor fokus på bedre samarbeid med primærhelsetjenesten, oppfølging av et ambulerende team, tidlig utreise fra sykehus og rehabilitering med utgangspunkt i hjemmet ble sterkt vektlagt. Den konstruerte behandlingskjeden ble evaluert med tanke på helsegevinst for den enkelte og bedre ressursutnytting sammenlignet med det tradisjonelle behandlingstilbudet. Studien ble gjennomført som en klinisk randomisert kontrollert studie der 320 pasienter med akutt hjerneslag ble inkludert. 160 pasienter fikk ordinær slagenhet behandling med videre institusjonsrehabilitering og/eller oppfølging av primærhelsetjenesten, mens de øvrige 160 pasienter fikk oppfølging av et ambulerende team i henhold til den nye og konstruerte behandlingskjeden. I de fire arbeidene som inngår i avhandlingen er det sett på risiko for alvorlig funksjonshemning og død, endring i funksjonsnivå og livskvalitet, samt kostnadsanalyser og ressursforbruk av helsetjenester. Pasientene i de to gruppene ble undersøkt og sammenlignet 6 og 12 måneder etter sykdomsdebut. Resultatene av studien viste at sammenlignet med tradisjonell behandling oppnådde pasientene i intervensjonsgruppen signifikant bedre funksjonsnivå (p=0.017) og redusert risiko for alvorlig funksjonshemning og død (p=0.044) etter ett år. De viste også tendens til bedret livskvalitet samtidig som initial liggetid i institusjon ble redusert med 40 % (p=0.032). Det var ingen økning i totalt ressursforbruk eller kostnader i intervensjonsgruppen. Oppsummert viser avhandlingen at en slagbehandlingskjede med fokus på samarbeid på tvers av forvaltningsnivå, oppfølging av et ambulerende team og rehabilitering mens pasientene bor hjemme gir meget positiv effekt. Den kliniske betydning av disse resultater er at en oppfølging i form av en slagbehandlingskjede i tillegg til akutt behandling i slagenhet bør inngå som en integrert del av behandlingstilbudet for denne pasientgruppen. Arbeidene er utført ved INM og ISM, Det medisinske fakultet, NTNU. 1.amanuensis, dr.med Bent Indredavik har vært hovedveileder og Professor dr.med Roar Johnsen biveileder. / Extended Stroke Unit Service and Early Supported Discharge. Short and Long-term Effects. Background and purpose Stroke imposes a considerable burden for patients, their caregivers and the society worldwide. It is a challenge to organise the healthcare service that can provide effective management of patients who have suffered from stroke. Several trials have shown that stroke unit care improves the outcome for stroke patients. More limited information exists about the most effective way to organise the follow-up care after the acute care in a stroke unit. Stroke patients conventionally receive a substantial part of their rehabilitation in hospital or in other institutions that offer 24 hours-stay. The primary aim of this thesis was to increase knowledge about the organising of follow-up care for stroke patients after the acute care in a stroke unit. To achieve this we performed a trial to evaluate the short and long-term effects of an extended stroke unit service (ESUS), with early supported discharge from hospital, co-operation with the primary health care, and more emphasize on rehabilitation at home as essential elements. Methods We performed a randomized controlled trial in which 320 acute stroke patients admitted to the Stroke Unit at St. Olavs Hospital, Trondheim University Hospital were included and allocated either to ordinary stroke unit care (OSUS) (160 patients) with further in-patient rehabilitation or follow-up from the primary healthcare service, or to stroke unit care with early supported discharge (160 patients). The ESUS consisted of a mobile team which co-ordinate early supported discharge and further rehabilitation. Included in this thesis are 4 papers based on data from this study population of acute stroke patients followed in one year after the onset of stroke. We wanted to compare the groups in relation to independency, quality of life (QoL) and resource use and costs. • Functional outcome were measured as the proportion of patients who were independent as assessed by modified Rankin Scale (RS)(RS&lt;2 =global independence) and Barthel Index (BI)(BI&gt;95 = independent in ADL) at 26 weeks and 52 weeks, the differences in final residence and analyses to identify patients who benefited most of an early supported discharge service (paper I and II). All assessments were blinded. • The outcome of QoL was measured by the Nottingham Health Profile (NHP) at 52 weeks. Other outcomes measured at 52 weeks were differences between the groups according to social activity, depression, cognitive function and the burden for carers’. (paper III). • The use of all health services during the first 52 weeks was recorded prospectively in both groups; its costs were measured as service costs and represent a combination of calculated average costs and tariffs. Hospital expenses were measured as costs per inpatient day. The secondary objectives were to explore differences in costs between the groups with respect to different types of services, time of service delivery and stroke severity (paper IV). Results • Extended stroke unit service with early supported discharge and co-ordination by a mobile team improves functional outcome 6 months and 12 months after stroke. The Odds Ratio for independence at one year was 1.56 (95% C.I, 1.01-to 2.44). It was most beneficial for patients with moderate stroke (papers I and II). • Extended stroke unit service with early supported discharge can improve long-term quality of life measured by global NHP. The ESUS group had a significant better QoL after one year than the OSUS group (p = 0.048). There were no significant differences between the groups in the secondary outcomes social activity, depression and cognitive function. The caregivers who got their patients early at home did not report an increased burden compared to caregivers whose patients became ordinary stroke unit care (paper III). • The length of initial institutional stay (hospital and rehab.clinic) were reduced with 40 % for the patients offered extended stroke unit service (18.6 days in the ESUS versus 31.1 days in the OSUS) (p=0.032). There was also a reduction in average number of total inpatient days during the first year in favour of the ESD group (p = 0.012) (paper IV). • The total health services costs for ESUS was equal or less than costs for ordinary care during the first year after stroke. There was a non-significant reduction in total mean service costs in the ESUS group (EUR 18937 / EUR 21824). The service seemed to be most cost effective for patients with moderate severity of stroke (23% lower mean costs compared to OSUS). The important cost savings caused by reduced length of institutional stay did not lead to an increase in costs for home-based rehabilitation (paper IV). Conclusion An extended stroke unit service with early supported discharge improved functional outcome and reduced the length of stay in institutions compared to traditional stroke unit care. It also seems that this service can improve long-term quality of life. The costs are equal or less than costs for ordinary care. An early, well organised discharge from hospital co-ordinated by a mobile team seems to be an important contribution in the treatment of stroke patients and should be considered, in addition to organised in-patient stroke unit care, as a part of a comprehensive stroke care.

Background Some degree of cognitive decline is a normal, non-clinical part of aging. Physical exercise has been suggested as one strategy which may improve cognition in nondemented older adults. The findings of randomised, controlled trials conducted since the 1980s have been promising, but not unequivocal, and much remains to be understood about the relationship between exercise and cognition in older adults. There have also been suggestions that combining exercise and cognitive training may be beneficial. There has, however, been only one reported study comparing the benefits of exercise training, and combined exercise and cognitive training (Fabre, Chamari, Mucci, Masse-Biron, & Prefaut, 2002). While combined training was reported to be even more effective than exercise training alone for improving cognition in older adults, the study had some substantial limitations. Aims The overall aims of this thesis were to further explore the effect of exercise training on cognition in older adults, and to compare exercise training alone with combined exercise and cognitive training. Following a narrative review of the relevant literature, this thesis is presented in two parts. In Part One a randomized, controlled trial comparing the impact of exercise training, and combined exercise and cognitive training, on the cognitive functioning, physical functioning, functional performance, and psychological well-being of communitydwelling older adults is presented. For Part One, there were three specific aims: (1) To assess the efficacy of a 16 week exercise program (relative to control), on measures of cognitive functioning, physical functioning, functional performance, and psychological well-being; (2) To compare the efficacy of the 16 week exercise program with that of a 16 week combined exercise and cognitive training program; and (3) To identify the physical, psychological and training factors associated with changes in cognitive and physical functioning from baseline to post-test. In Part Two a qualitative evaluation of older adults’ experiences and perceptions of exercise training, and combined exercise and cognitive training, is presented. Methods Thirty-nine community dwelling, older adults (aged between 60 and 80 years) were randomly allocated to one of three groups: Exercise, Combination or Control. Participants in the Exercise group attended three aerobic and strength training sessions per week for 16 weeks. Participants in the Combination group attended two aerobic and strength training sessions, and one cognitive training session, per week for 16 weeks. Participants in the Control group were contacted every four weeks. Assessments were conducted at baseline, post-test (16 weeks) and six-month follow-up (40 weeks). Measures of physical function, cognitive function, functional performance, and psychological wellbeing were collected, along with anthropometric and physiological measures. For the qualitative evaluation, participants from the Exercise and Combination groups provided written feedback to questions about their experiences of the two training programs and their perceptions of the outcomes. These qualitative data were collected after post-test. Results Significant within-group improvements in physical and cognitive function, from baseline to post-test, were seen in Exercise and Combination participants. Combination participants also showed significant within-group reductions in symptoms of anxiety and depression. There were, however, only a few significant between-group differences among Exercise and Control participants, and among Exercise and Combination participants. There were no significant within-group improvements in functional performance, from baseline to post-test, among Exercise or Combination participants. Six-month follow-up data were difficult to interpret, due to the paucity of between-group differences at post-test and the small sample size. There were several significant associations between physical, psychological and training factors, and changes in cognitive and physical functioning. The most pertinent finding was that baseline functioning was consistently associated with change, such that participants with low baseline scores were most likely to improve from baseline to posttest. In the qualitative evaluation participants reported positive experiences of the training programs and reported improvements in physical, cognitive, functional and psychological wellbeing. Participants also highlighted components of the programs which require improvement and made recommendations for future programs. Conclusions The results of this thesis provide some cautious support for the notion that exercise, and combined exercise and cognitive training, may result in small improvements in cognition, physical functioning, and psychological well-being in older adults. Some of the findings must be interpreted with caution, however, given the small sample size. More research is required into the functional (or ‘real world’) impact of this type of training, the long-term effects of training, and the factors associated with changes in cognitive and physical function. Based on these findings, recommendations for the development and implementation of future research were made. As the population ages and the public health burden attributable to aging increases, research into the development and efficacy of programs to enhance well-being and independence in older adults is of great importance.

Rationale Within Australia, cardiac rehabilitation attendance is poor, with typically thirty percent of eligible patients attending programs. The majority of cardiac patients are not receiving the support or detailed information required to increase physical activity participation after hospitalisation. Further, many cardiac patients are not exercising independently, regardless of their attendance at cardiac rehabilitation. As physical activity is important in the prevention and treatment of heart disease, there could be substantial benefits to the individual and cost savings for the health system if cardiac patients were more active. Physical activity interventions based on social cognitive theory have demonstrated success in improving physical activity among people with chronic diseases. However, there is little research conducted with cardiac patients, in particular, with those who do not attend cardiac rehabilitation. This research addresses this gap in public health practice by providing an intervention to cardiac patients, irrespective of their attendance at cardiac rehabilitation, thereby addressing a population that is often overlooked and hard to reach. Research aims ?? To determine the uptake rate of cardiac rehabilitation in the north Illawarra and Shoalhaven areas of New South Wales and identify the characteristics of cardiac rehabilitation attendees and non attendees. ?? To evaluate the efficacy of a pedometer based physical activity intervention in cardiac patients referred to cardiac rehabilitation. Methodology This thesis consisted of three related studies: a cross sectional analysis of the characteristics of cardiac rehabilitation referrals (n = 944) over a 10 month period; and two randomised controlled trials conducted simultaneously. The Cardiac Rehabilitation Trial participants (n = 110) were patients who had attended cardiac rehabilitation; Community Trial participants (n = 215) were those who did not attend cardiac rehabilitation. The six week intervention evaluated in the trials included self monitoring of daily physical activity using a pedometer and step calendar, and two behavioural counselling and goal setting sessions delivered via telephone. Additional support for intervention group participants was provided through two brief telephone calls made after the six week intervention period. Self reported physical activity levels were collected at baseline, six weeks and six months. The questionnaire also collected information about psychosocial factors affecting physical activity participation. The exercise capacity of the participants in the Cardiac Rehabilitation Trial was objectively measured at baseline, six weeks and six months using a gas exchange analysis system. Results The cardiac rehabilitation uptake rate was 28.8 per cent of referred patients. Cardiac rehabilitation attendees were significantly younger and more likely to have had a coronary artery bypass graft surgery (CABGS) or percutaneous coronary intervention (PCI) procedure than non attendees. Study groups in both trials were not significantly different at baseline. In the Cardiac Rehabilitation Trial, improvements in total weekly physical activity sessions (p=0.002), walking time (p=0.013) and walking sessions (p<0.001) in the intervention group were significantly greater than the change in the control group at the end of the six week intervention. At six months, improvements in the intervention group remained significantly greater than the control group in total physical activity time (p=0.044), total physical activity sessions (p=0.016) and walking sessions (p=0.035) after adjusting for baseline differences. These self reported behavioural changes were corroborated by improvements in cardiorespiratory fitness at six months in the intervention group (p=0.010). Improvements in the intervention group in behavioural (p=0.039) and cognitive (p=0.024) self management strategy use were significantly greater than the controls at six weeks after adjusting for baseline differences. The improvement in cognitive strategy use (p=0.001) remained significantly greater in the intervention group compared to controls at six months after adjusting for baseline differences. Self efficacy, outcome expectancies and psychological distress were not significantly different between groups at six weeks or six months after adjusting for baseline differences. In the Community Trial, improvements in total weekly physical activity time (p=0.027), total physical activity sessions (p=0.003), walking time (p=0.013) and walking sessions (p=0.002) in the intervention group were significantly greater than the control group at six weeks after adjusting for baseline differences. At six months, improvements in total physical activity time (p=0.015), total physical activity sessions (p=0.019), walking time (p=0.002) and walking sessions (p=0.026) in the intervention group remained significantly greater than the control group after adjusting for baseline differences. Improvements in outcome expectancies (p=0.038) and cognitive self management strategy use (p=0.028) in the intervention group were significantly greater than the change in the control group at six weeks, after adjusting for baseline differences. However, these differences did not remain significant at six months. Conclusion This research showed that participation in a six week pedometer based intervention significantly increased the physical activity level and psychosocial status of people with heart disease. These findings suggest the pedometer based intervention could be offered as an effective and accessible option for those who do not attend cardiac rehabilitation to increase their physical activity levels. This intervention could also be promoted as an important adjunct to existing cardiac rehabilitation programs to promote adherence to physical activity after cardiac rehabilitation attendance. These studies provide community based evidence of an effective physical activity intervention for those eligible for cardiac rehabilitation, including those who do not attend. This provides a public health approach to cardiac rehabilitation programs and has the potential to improve health outcomes in this population.

Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting an estimated 1% of the global population. Joint protection is one intervention with some quality evidence of efficacy for RA self-management. However, joint protection education is often provided only in urban centres during Arthritis Self-Management Programs (ASMPs) in classroom sessions at designated times. These programs, therefore, may not be available to all who need them. Providing and testing more accessible methods of delivering joint protection education to people living with RA may improve accessibility. Aims: (i) To develop a virtual world (VW) intervention available via the Internet in Second Life®, that aims to improve the knowledge of joint protection among people with RA and (ii) to undertake a pilot randomised controlled trial (RCT) to assess the feasibility of conducting a subsequent large scale RCT. Methods: First, qualitative interviews with occupational therapists and clients living with RA who had previous experiences teaching or taking arthritis self-management programmes were undertaken and thematically analysed. This analysis informed the design of the VW joint protection education intervention. Second, the intervention was constructed and tested with these same participants. Their feedback helped refine the VW intervention and select assessment tools for the pilot RCT. Third, in a pilot RCT, three primary methods of advertising and invitation were used to recruit subjects: (i) poster invitations with take-home paper copies from clinical settings; (ii) direct messages to Twitter® users living with RA; and (iii) online discussion forums. Participants were recruited after contacting the principal investigator, reading an invitation letter and giving written informed consent. Participants were randomised to intervention or (30-day) waiting list control group, and completed a series of measures. These were completed after 30 days of program access for the treatment group and on enrolment in the study for the control group. Survey completion was online and included piloted knowledge-based questions about joint protection, validated during the second phase of the study with occupational therapists who were experts in joint protection education. A higher score was indicative of better joint protection knowledge. Standardized measures used on the survey included the Arthritis Impact Measurement Scale, Short Form, version II (AIMS2SF) and Pain Self-Efficacy Questionnaire (PSEQ). Results: It was possible to develop a VW education program focused on RA and joint protection based on the content identified by participants in the first part of the study and test with the tools selected. The program developed included input from client users, following the theorectical basis of occupational therapy as a client-centred practice. Additionally, the program developed applied principles of adult-learning and the recommendations of existing programs regarding chronic disease management. Recruitment of 50 participants for the pilot RCT was challenging, taking 6 months with low response rates for all three methods. The poorest response rates were to poster and paper invitations in clinical settings. The most effective means of recruitment was via electronic bulletin boards, such as blogs. All subjects, once randomised to the control or intervention group completed the online questionnaire. However, adherence to the intervention was poor; only 15 out of 25 randomised reported using the program. On the other hand, all 15 who used the program indicated that this medium was acceptable to learn about joint protection, despite 5/15 of these subjects reporting some difficulty accessing the program. All participants completed the three questionnaires (knowledge, impact, pain self-efficacy) and these may be useful in a definitive RCT. Although the main purpose of using Intention to Treat Analysis in pilot studies is to practice and check that analysis is feasible, there was a positive statistically significant difference between the treatment (x̄=52.8%) and control (x̄=24%) group scores on a test of joint protection knowledge using an independent samples t-test (F value, 20.8 p < 0.05) comparing joint protection knowledge scores after the treatment group had access to the program for 30 days. A higher score was indicative of better joint protection knowledge. The difference between the two groups was considerable, with the intervention group score mean being more than double that of the control group. Given the magnitude of this difference between groups, a smaller difference between groups would also be worth finding. The difference between groups for the AIMS2SF and PSEQ were not statistically significant using an independent samples t-test (F values, 0.5 and 0.2) but there was some suggestion that the intervention group scored more favourably on some of the subscales more relevant to joint protection on both the AIMS2SF and PSEQ, particularly noteworthy was a higher score pertaining to ability to carry out work on both measures. In a definitive trial a sample size of 1250 participants would give 80% power to find a difference of 28.8% on joint protection knowledge, weighted score of 1.8 on the AIMS2SF and overall score of 1.8 on the PSEQ at 5% level of significance. Smaller samples would be required if the PSEQ was dropped as a measure in a future study. Sample sizes of 14 and 558 would be required for the joint protection knowledge and AIMS2SF respectively at the same level of power and significance. Conclusion: A VW intervention to improve joint protection knowledge has been developed and is worth testing further. The intellectual contribution of the creation of this program using this methodology is that an occupational therapy based study using client input and priniciples of adult learning to create the intervention has been conducted, applying client-centred practice in research, which is, in reality, present in a minority of studies at this time. A full RCT would be feasible, though very challenging, given the numbers of subjects required for recruitment, most likely recruiting via the Internet on relevant RA focus sites, such as RA bloggers, and using the same outcome measures as in this study. A sample size of 1250 could feasibly be recruited in 36 months if a full time study were undertaken with suggestions discussed to assist with future study recruitment. However, given the number of study dropouts at enrolment seen in this study, close to double this number would be needed, entailing a recruitment period of up to 72 months, or 6 years, making a full RCT less practical. A future study may need to consider either a longer enrolment period, different outcome measures as well as address the limitations of this study, including the limited time of enrolment in this pilot RCT. However, longer enrolment duration would increase the amount of time required for a future full RCT, reducing the feasibility of a future study. Findings from this study indicate that the program developed would likely to be useful to people who are not able to access the urban centred classroom based program. On the other hand, those participants who used the program incurred no costs, appeared to have no risks or detrimental impact with possible improvement in knowledge and self-efficacy. Now the intervention has been developed, refinement, maintenance, and use is low cost for service providers, so it could be used routinely now for those who prefer it to ASMPs with an ongoing preference trial.

Objectives: This thesis includes two distinct pieces of work. A systematic literature review (SLR) aimed to identify, organise and evaluate constructs and measures of adjustment and adaptation to retirement (AAR), as these are currently used in the literature. A meta-analysis (MA) sought to systematically evaluate the evidence of the relationship between retirement and self-reported symptoms of depression in later life. Methods: For the SLR, a comprehensive list of electronic databases, and additional sources, were searched (March-May 2013). The identified constructs of AAR were evaluated in relation to their content, clarity and frequency of use. The identified measures were evaluated in relation to pre-defined psychometric properties and frequency of use. For the MA, an equally comprehensive search strategy was used (December 2012-March 2013). A metaanalysis and systematic assessment of risk of bias were carried out on the studies eventually included. Results: In the SLR, 27 measures of AAR were put forward for evaluation, and 6 distinct clusters of constructs of AAR were identified. AAR is defined inconsistently in this literature. Most measures that are used to assess these constructs are adapted or imported from other contexts (e.g. mental health, well-being, life-satisfaction). The 7 measures that related specifically to AAR (‘retirement satisfaction and role adjustment’) lacked detailed psychometric information. Eight non-randomised studies were included in the MA, 5 cohort studies and 3 cross-sectional studies. Studies were grouped and analysed according to these two design-type subgroups There was evidence of high dispersion of effect sizes, variable risk of bias and methodological and statistical heterogeneity between studies in both sub-groups – cohort (Q=640.728, df =4, p<0.001), cross-sectional (Q=76.611, df=2, p<0.001). Summary effects were therefore not meaningful. Sensitivity and sub-group analyses did not account for high heterogeneity of effect sizes. Conclusions: The SLR concluded that the variability in outcomes of research on AAR found in this literature may be underpinned, in part, by the different constructs and measures that are used. The 27 measures evaluated did not seem, at face-value, to measure the same construct; their psychometric properties also varied. The interpretation of outcomes, and comparisons between studies, in this area is hindered by this inconsistency. The MA concluded that the relationship between retirement and self-reported depressive symptoms seems to be complex and variable. Effect-sizes of individual studies were small, non-significant and highly dispersed, and heterogeneity of true effects was high. These results may be limited by confounding factors in primary studies. This is discussed and contextualised in relation to the use of non-randomised studies in meta-analysis.

No description available.

Background: There is an established need to manage teasing and bullying of children who stutter (CWS) through changing the attitudes of their peers. The intervention, the Classroom Communication Resource (CCR), was implemented by teachers in classrooms. The primary objective of the main study was to determine the effectiveness of the CCR through a cluster Randomised Controlled Trial (RCT). The secondary objective of this study was to determine the treatment effect of the Stuttering Resource Outcomes Measure (SROM) within the subscales of Positive Social Distance (PSD), Social Pressure (SP) and Verbal Interaction (VI). The subgroup objective was to determine the primary objective between and across lower and higher school quintile clusters. Method: A cluster RCT was conducted. Participants in grade 7, aged 11 years and older, were randomly assigned to control and intervention groups using school and subgroup (quintile) clusters classifications. Following randomisation, stratification took place using a 1:1 allocation ratio. Participants viewed a video of a child who stuttered at baseline. Teachers administered the CCR (social story, role-play, discussion) in intervention groups only over a 60-90 minute session after they received an hour of training. Peer attitudes were measured at baseline and at 6 months post-intervention using the SROM in intervention and control groups. Results: A total of 10 schools were included whereby they were randomly allocated to control (k=5) and intervention groups (k=5). Within the schools, 454 participants were included with n =223 participants in the intervention and n= 231 in the control group. The study showed no statistically significant difference on the global SROM score (mean difference: -0.11 [95% confidence interval: -1.56, 1.34]; p = 0.88). Similarly, no significant differences were noted on SROM subscales: PSD (1.04 [-1.02,311]; p =0.32), SP (-0.45 [-1.22, 0.26]; p=0.21) and VI (0.05 [-1.01, 1.11]; 0.93), the secondary objective of this study. No significant subgroup effect on the global SROM score (lower vs higher quintile subgroups) [interaction p-value = 0.52] was observed during subgroup analysis. Results were however consistent with the hypothesis and quintile subgroups behaved similarly. Results were found clinically important when considering confidence intervals as well as the magnitude and direction of treatment effect. Conclusion: While the treatment effect showed no statistically significant differences on the global SROM and within the constructs of PSD, SP and VI, a clinically important result was noted when evaluating the meaningfulness of this study as well as its implications. Subgroup analysis showed that the quintiles behaved similarly, showing that the CCR was appropriate for schools within the lower and higher quintiles.