Australian New Zealand Clinical Trials Registry Research Articles

Fasting as an intervention to alter the impact of simulated night-shift work on glucose metabolism in healthy adults: a cluster randomised controlled trial.

Night-shift work causes circadian misalignment and impairs glucose metabolism. We hypothesise that food intake during night shifts may contribute to this phenomenon. This open-label, multi-arm, single-site, parallel-group controlled trial involved a 6 day stay at the University of South Australia's sleep laboratory (Adelaide, SA, Australia). Healthy, non-shift-working adults without obesity (N=55; age 24.5 ± 4.8 years; BMI 24.8 ± 2.8 kg/m2) were assigned to the next available run date and cluster randomised (1:1:1) to fasting-at-night (N=20), snack-at-night (N=17), or meal-at-night (N=18) conditions. One participant withdrew from each group, prior to starting the study. Due to study design, neither participants nor people collecting their measurements could be blinded. Statistical and laboratory staff were concealed to study allocation. Participants were fed at calculated energy balance, with the macronutrient composition of meals being similar across conditions. The primary outcomes were a linear mixed-effects model of glucose, insulin and NEFA AUC in response to a 75 g OGTT that was conducted prior to and after 4 consecutive nights of shift work plus 1 night of recovery sleep. Insulin sensitivity, insulinogenic and disposition indexes were also calculated. Night-shift work impaired insulin sensitivity, as measured by insulin AUC (p=0.035) and the insulin sensitivity index (p=0.016) across all conditions. Insulin secretion, as measured by the insulinogenic index, was increased in the fasting-at-night condition only (p=0.030), resulting in a day×condition interaction in glucose AUC (p<0.001) such that glucose tolerance was impaired in the meal-at night (+2.00 [95% CI 1.45, 2.56], p<0.001) and snack at-night (+0.96 [0.36, 1.56], p=0.022) conditions vs the fasting-at-night (+0.34 [-0.21, 0.89]) condition. A day×condition interaction was also observed in NEFA AUC (p<0.001), being higher in the meal-at-night (+0.07 [0.03, 0.10]. p=0.001) and snack-at-night (0.01 [-0.03, 0.05], p=0.045) conditions vs the fasting-at-night condition (-0.02 [-0.06, 0.01]). No adverse events occurred. The timing of food intake has a critical effect on glucose metabolism during simulated night-shift work, which was readily amendable to a meal re-timing intervention. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001556437 FUNDING: This work was funded by the National Health and Medical Research Council (NHMRC), APP1099077.

Participant Motivators and Expectations in the MEL-SELF Randomized Clinical Trial of Patient-Led Surveillance for Recurrent Melanoma: Content Analysis of Survey Responses.

Limited data exist on the motivations and expectations of participants when enrolling in dermatology clinical trials, including melanoma early detection trials. Understanding participant motivators for research engagement has been identified as a prioritized area for trial methodology research. The study aimed to determine motivators of participation and expectations from trial involvement among patients enrolled in the MEL-SELF randomized clinical trial of patient-led surveillance for new or recurrent melanoma. The MEL-SELF trial is recruiting patients previously treated for localized melanoma, who own a smartphone, have a partner to assist with skin self-examination (SSE), and attend routinely scheduled follow-up at specialist and primary care skin clinics in Australia. We evaluated responses from the first 100 randomized participants to 2 open-ended questions about their motivations and expectations for participating in the trial, administered through the internet-based baseline questionnaire. A total of 3 coders independently coded the free-text responses and resolved discrepancies through consensus. Qualitative content analysis by an iterative process was used to group responses into themes. Responses from potential participants who were not randomized and the 404 participants randomized subsequently into the trial, were also checked for new themes. Coding and analysis were conducted in Microsoft Excel. Out of the 100 survey participants, 98 (98%) answered at least 1 of the 2 questions. Overall, responses across the motivation and expectation items indicated 3 broad themes: community benefit, perceived personal benefit, and trusting relationship with their health care provider. The most common motivators for participation were related to community benefit. These included progressing medical research, benefitting future melanoma patients who may have similar experiences, and broader altruistic sentiments such as "helping others" or "giving back." The most common expectations from the trial related to personal benefit. These included perceived improved outcomes such as earlier diagnosis and treatment, access to additional care, and increased self-empowerment to take actions themselves that benefit their health. Patients expressed a desire to gain health-related knowledge and skills and were interested in the potential advantages of teledermatology. There were no new themes in responses from those who were not randomized or were randomized subsequent to the first 100. We report a tailorable, patient-focused approach to identify drivers of research engagement in clinical research. Clinical trials offer an opportunity to collate a substantial evidence base on determinants of research participation and to identify context-specific factors. Results from the MEL-SELF trial emphasized notable altruism, self-empowerment, and perceived advantages of teledermatology as specific motivators. These findings informed consent processes, recruitment, retention, response to trial tasks, and intervention adherence for the MEL-SELF host trial. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379527.

Integrated model of secondary fracture prevention in primary care (INTERCEPT): protocol for a cluster randomised controlled multicentre trial

BackgroundOsteoporotic fractures signal severely compromised bone strength and are associated with a greatly increased risk of refracture. Despite the availability of effective and safe medications that reduce fracture risk, 70–80% of patients are inadequately investigated or treated for osteoporosis following an initial fracture, constituting a significant ‘osteoporosis care gap’. Optimal methods of bridging this gap with primary care at the forefront of secondary fracture prevention remain undetermined. This protocol describes a cluster randomised controlled trial to evaluate the effectiveness of a novel integrated model of secondary fracture prevention and management in primary care.MethodsThe cluster randomised controlled trial involves multiple branches of a community-based radiology provider (CRP), a hospital-based secondary fracture prevention program (SFPP) and numerous primary care practices in metropolitan Sydney that refer to either the CRP or SFPP. Using natural language processing tools, patients diagnosed with a potential osteoporotic fracture will be identified by automatically screening radiology reports generated at the CRP or SFPP. The primary care practices that these patients attend will be randomised (1:1) to either the intervention or usual care. The intervention consists of (i) electronic and fax alerts informing the practice/primary care physician that their patient has been diagnosed with a potential osteoporotic fracture; (ii) provision of osteoporosis management guidelines and (iii) follow-up surveys at 4 weeks and 6 months. Practices in the usual care (control) group will receive no alerts and provide usual care. The primary outcome is the proportion of patients undergoing a bone density scan and/or filling a prescription for osteo-protective pharmacotherapy within 3 months of the initial diagnostic imaging report. Secondary outcomes are the proportion of patients: (i) undergoing an osteoporosis-related blood test within 3 months of the initial diagnostic imaging report; (ii) initiated on a chronic disease management plan within 3 months of the diagnostic report, and (iii) filling a second prescription for osteo-protective pharmacotherapy within 9 months post initial diagnostic imaging report. Outcomes will be obtained through de-identified linked data from Medical Benefits Schedule and Pharmaceutical Benefits Scheme held by the Australian Institute of Health and Welfare.DiscussionThis is the first randomised trial to integrate case-detection of potential osteoporotic fractures in a hospital and community setting with direct alerts to the patient’s primary care provider. This study will determine whether such an intervention is effective in improving investigation and/or treatment rates of osteoporosis in patients with a potential osteoporotic fracture.Trial registrationThis study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000658617p.

Study protocol: Optimising patient positioning for the planning of accelerated partial breast radiotherapy for the integrated magnetic resonance linear accelerator: OPRAH MRL

BackgroundAccelerated partial breast irradiation (APBI) is an accepted treatment option for early breast cancer. Treatment delivered on the Magnetic Resonance integrated Linear Accelerator (MRL) provides the added assurance of improved soft tissue visibility, important in the delivery of APBI. This technique can be delivered in both the supine and prone positions, however current literature suggests that prone treatment on the MRL is infeasible due to physical limitations with bore size. This study aims to investigate the feasibility of positioning patients on a custom designed prone breast board compared with supine positioning on a personalised vacuum bag. Geometric distortion, the relative position of Organs at Risk (OAR) to the tumour bed and breathing motion (intrafraction motion) will be compared between the supine and prone positions. The study will also investigate the positional impact on dosimetry, patient experience, and position preference.MethodsUp to 30 patients will be recruited over a 12-month period for participation in this Human Research Ethics Committee approved exploratory cohort study. Patients will be scanned on the magnetic resonance imaging (MRI) Simulator in both the supine and prone positions as per current standard of care for APBI simulation. Supine and prone positioning comparisons will all be assessed on de-identified MRI image pairs, acquired using appropriate software. Patient experience will be explored through completion of a short, anonymous electronic survey. Descriptive statistics will be used for reporting of results with categorical, parametric/non-parametric tests applied (data format dependent). Survey results will be interpreted by comparison of percentage frequencies across the Likert scales. Thematic content analysis will be used to interpret qualitative data from the open-ended survey questions.DiscussionThe results of this study will be used to assess the feasibility of treating patients with APBI in the prone position on a custom designed board on the MRL. It may also be used to assist with identification of patients who would benefit from this position over supine without the need to perform both scans. Patient experience and technical considerations will be utilised to develop a tool to assist in this process.Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1262400067583. Registered 28th of May 2024. https://www.anzctr.org.au/ACTRN12624000679583.aspx

Data-Driven Implementation Strategy to Optimise Clinician Behaviour Change at Scale in Complex Clinical Environments: A Multicentre Emergency Care Study.

To develop an evidence-driven, behaviour change focused strategy to maximise implementation and uptake of HIRAID (History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) in 30 Australian rural, regional and metropolitan emergency departments. An embedded, mixed-methods study. This study is the first phase of a step-wedge cluster randomised control trial of HIRAID involving over 1300 emergency nurses. Concurrent quantitative and qualitative data were collected via an electronic survey sent to all nurses to identify preliminary barriers and enablers to HIRAID implementation. The survey was informed by the Theoretical Domains Framework, which is a synthesis of behavioural change theories that applies the science of intervention implementation in health care to effect change. Quantitative data were analysed using descriptive statistics and qualitative data with inductive content analysis. Data were then integrated to generate barriers and enablers to HIRAID implementation which were mapped to the Theoretical Domains Framework. Corresponding intervention functions and Behaviour Change techniques were selected and an overarching implementation strategy was developed through stakeholder consultation and application of the APEASE criteria (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety and Equity). Six barriers to HIRAID implementation were identified by 670 respondents (response rate ~58%) representing all 30 sites: (i) lack of knowledge about HIRAID; (ii) high workload, (iii) lack of belief anything would change; (iv) not suitable for workplace; (v), uncertainty about what to do and (vi) lack of support or time for education. The three enablers were as follows: (i) willingness to learn and adopt something new; (ii) recognition of the need for something new and (iii) wanting to do what is best for patient care. The 10 corresponding domains were mapped to seven intervention functions, 21 behaviour change techniques and 45 mechanisms. The major components of the implementation strategy were a scaffolded education programme, clinical support and environmental modifications. A systematic process guided by the behaviour change wheel resulted in the generation of a multifaceted implementation strategy to implement HIRAID across rural, regional and metropolitan emergency departments. Implementation fidelity, reach and impact now require evaluation. HIRAID emergency nursing assessment framework reduced clinical deterioration relating to emergency care and improved self-confidence and documentation in emergency departments in pilot studies. Successful implementation of any intervention in the emergency department is notoriously difficult due to workload unpredictability, the undifferentiated nature of patients and high staff turnover. Key barriers and enablers were identified, and a successful implementation strategy was developed. This study uses theoretical frameworks to identify barriers and enablers to develop a data-driven, behavioural-focused implementation strategy to optimise the uptake of HIRAID in geographically diverse emergency departments which can be used to inform future implementation efforts involving emergency nurses. The CROSS reporting method (Supporting Information S3) was used to adhere to EQUATOR guidelines. No Patient or Public Contribution. Australian New Zealand; Clinical Trials Registry (ANZCTR) number: ACTRN12621001456842, registered 25/10/2021.

Exploring the Feasibility of Digital Voice Assistants for Delivery of a Home-Based Exercise Intervention in Older Adults With Obesity and Type 2 Diabetes Mellitus: Randomized Controlled Trial.

Current clinical guidelines for the management of type 2 diabetes mellitus (T2DM) in older adults recommend the use of antihyperglycemic medications, monitoring of blood glucose levels, regular exercise, and a healthy diet to improve glycemic control and reduce associated comorbidities. However, adherence to traditional exercise programs is poor (<35%). Common barriers to adherence include fear of hypoglycemia and the need for blood glucose level monitoring before exercise. Digital health strategies offer great promise for managing T2DM as they facilitate patient-practitioner communication, support self-management, and improve access to health care services for underserved populations. We have developed a novel web-based software program allowing practitioners to create tailored interventions and deliver them to patients via digital voice assistants (DVAs) in their own homes. We aim to evaluate the feasibility of a 12-week, home-based, personalized lifestyle intervention delivered and monitored by DVAs for older adults with obesity and T2DM. In total, 50 older adults with obesity aged 50-75 years with oral hypoglycemic agent-treated T2DM were randomized to the intervention (DVA, n=25) or a control group (n=25). Participants allocated to the DVA group were prescribed a home-based muscle strengthening exercise program (~20- to 30-min sessions) and healthy eating intervention, delivered via DVAs (Alexa Echo Show 8; Amazon) using newly developed software ("Buddy Link"; Great Australian Pty Ltd). Control group participants received generalized physical activity information via email. Outcomes were feasibility, DVA usability (System Usability Scale), and objectively assessed physical activity and sedentary time (wrist-worn accelerometers). In total, 45 (90%) out of 50 participants completed this study. Mean adherence to prescribed exercise was 85% (SD 43%) with no intervention-related adverse events. System usability was rated above average (70.4, SD 16.9 out of 100). Compared with controls, the DVA group significantly decreased sedentary time (mean difference -67, SD 23; 95% CI -113 to -21 min/d), which was represented by a medium to large effect size (d=-0.6). A home-based lifestyle intervention delivered and monitored by health professionals using DVAs was feasible for reducing sedentary behavior and increasing moderate-intensity activity in older adults with obesity and T2DM. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000307808; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381364&isReview=true.

Obstructive sleep apnea and cerebral small vessel disease in community-based older people: an aspirin in reducing events in the elderly imaging substudy

Abstract Study Objectives Obstructive sleep apnea (OSA) may increase the risk of dementia. A potential pathway for this risk is through cerebral small vessel disease (CSVD). In the context of an existing randomized trial of aspirin for primary prevention, we aimed to investigate OSA’s impact on CSVD imaging measures and explore whether aspirin effects these measures over 3 years that differ in the presence or absence of OSA. Methods A substudy of the aspirin in reducing events in the elderly (ASPREE) randomized placebo-controlled trial of low-dose aspirin. Community-dwelling participants aged 70 years and above, without cognitive impairment, cardiovascular disease, or known OSA completed an unattended limited-channel sleep study that calculated the oxygen desaturation index and apnea–hypopnea index. At baseline and 3 years later, volumes of white matter hyperintensities (WMH) and silent brain infarctions (SBI) were measured on 1.5 Tesla brain magnetic resonance imaging, and retinal vessel calibers were calculated from retinal vascular imaging. Results Mild and moderate/severe OSA was detected in 48.9% and 29.9%, respectively, of the 311 participants, who had a mean age of 73.7 years (SD 3.4 years), 38.6% female. OSA of any severity was not associated with WMH volumes, SBI, nor retinal vessel calibers at baseline, nor with change in these measures in the 277 participants with repeated measures acquired after 3 years. OSA of any severity did not interact with aspirin on change in these measures over 3 years. Conclusions In healthy older adults undiagnosed OSA was not associated with retinal vascular calibers and neuroimaging measures of CSVD. Clinical Trial Information ASPREE trial has registration with the International Standard Randomized Controlled Trial Number (ISRCTN) www.isrctn.com, ISRCTN83772183 and with www.clinicaltrials.gov, NCT01038583. SNORE-ASA has registration with the Australian New Zealand Clinical Trials Registry (ANZCTR) at www.anzctr.org.au, ACTRN12612000891820.

Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference -1.7%; 95% confidence interval -7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 .

Effectiveness of Cosmos caudatus Extract in Improving Health-Related Parameters among Older Adults with Sarcopenia: A Study Protocol

This is a randomized, two-arm, double-blind, placebo-controlled study that will be performed among older adults in Kelantan, Malaysia, for 12 weeks. This study aims to determine the effectiveness of a 12-week Cosmos caudatus (C. caudatus) extract supplementation on dietary intake, cognition, mental health, sleep quality, disability, gut microbiota, physical activity, frailty, metabolites, and protein synthesis pathways among older adults with sarcopenia. This study will involve 64 older adults diagnosed with sarcopenia that will be enrolled and randomly allocated with 1:1 ratio, where 32 subjects required in both intervention and placebo group. The intervention group will receive 500 mg/day of C. caudatus supplementation, while the placebo group will be given 500 mg/day of maltodextrin. Study outcomes including sarcopenia status, dementia, motoric cognitive risk, dietary pattern, anthropometric data, physical fitness, mental health, disability and sleep quality will be measured. Blood will be taken for analysis of protein synthesis pathways (using blood plasma) and untargeted metabolomics at baseline and the 12th week. Fecal sample will be collected from a subsample of 24 subjects for gut microbiota analysis. This study is one of the pioneers randomized controlled trials to evaluate C. caudatus efficacy on various health related outcomes among sarcopenic community-dwelling elderly. This study findings are hoped to have the potential to improve health awareness of ulam or fresh salad consumption, specifically C. caudatus and prove its effectiveness as a nutraceutical product for older adults with sarcopenia. The Australian New Zealand Clinical Trials Registry (ANZCTR) has this trial listed as registered with code (ACTRN12623000046606p).

A Qualitative Investigation of a Prenatal Mindfulness Relationship-Based (PMRB) Program to Support Maternal Mental Health and Mother–Baby Relationship During Pregnancy and Post-Partum

BackgroundPregnancy and the postpartum period are times of significant transition for women, with changes in maternal physical and mental health. The formation of a relationship between a mother and her baby is vital and has been recognised as laying the foundation for later child development. There is considerable evidence that this early relationship is influenced by a woman’s well-being during pregnancy and in the early post-partum period. Mindfulness-based programs have previously revealed positive outcomes, primarily in reducing maternal stress, anxiety, and depression. However, there remains a need for considering the influence of mindfulness on the mother-baby relationship and embodiment during pregnancy and the first trimester post-partum. This study aimed to conduct an in-depth exploration of pregnant women’s experiences of a nine-session prenatal mindfulness relationship-based (PMRB) program to support its feasibility.MethodsInformation about pregnant women’s (n = 13) experiences of the PMRB program was collected through online interviews during the sessions, including their birth stories. Responses to an open-ended question about how the program had supported them during pregnancy, labour/birth, and the first post-partum trimester were summarised using thematic analysis.ResultsSixteen themes were identified and organised in four categories: (1) expectations and motivations (healthy pregnancy and mental health, non-medicalised birth, contribution to the field); (2) experiences of the PMRB program (positive experiences, shared experience, engagement with mindfulness practices, pain, stress, and anxiety relief); (3) changes attributed to the PMRB program (a new way of responding to stressors, trusting the process, connecting to body, breath, and unborn baby, awareness of the unborn baby as a sentient being); (4) changes attributed to the mindfulness practice (increased mindfulness/self-awareness, stop look listen, embracing the moment, acceptance).ConclusionsThe evaluation suggested the PMRB program may help women cope with pain and emotional challenges and be more connected to their bodies and infant. The program may also help women become more aware of their unborn baby as a sentient being and the influence of their health and mental well-being on the baby development and health. Furthermore, the program may facilitate the mother-baby relationship during pregnancy, post-partum, and breastfeeding.PreregistrationThe trial has been successfully registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) following ethical approval from Bond University Human Research Ethics Committee (BUHREC—Application AS03534, approved 20 December 2022) and allocated the Australian clinical trials registration number (ACTRN): ACTRN12623000679684.

SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas

BackgroundComplete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC.MethodsSCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included.DiscussionBetter classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options.Trial registrationThe SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).

Process evaluation of a data-driven quality improvement program within a cluster randomised controlled trial to improve coronary heart disease management in Australian primary care.

This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states. Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices. Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention. Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions. Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

The Exercise Right for Active Ageing study: A pre-post evaluation of health-related quality of life and cost-utility in older Australians following a 12-week exercise programme

ObjectivesTo determine the effect of a 12-week subsidised exercise programme on health-related quality of life (HRQoL) in community-dwelling older Australians, and the cost-utility of the programme. DesignQuasi-experimental, pre-post study. MethodsParticipants included community-dwelling older adults, aged ≥65 years, from every state and territory of Australia. The intervention consisted of 12 one-hour, weekly, low-to-moderate-intensity exercise classes, delivered by accredited exercise scientists or physiologists (AESs/AEPs). Health-related quality of life was measured before and after programme participation using the EQ-5D-3L and converted to a utility index using Australian value tariffs. Participant, organisational and service provider costs were reported. Multivariable linear mixed models were used to evaluate the change in HRQoL following programme completion. Cost-utility outcomes were reported as incremental cost-effectiveness ratios (ICERs), based on programme costs and the change in utility scores. Results3511 older adults (77 % female) with a median (IQR) age of 72 (69–77) years completed follow-up testing. There was a small improvement in EQ-5D-3L utility scores after programme completion (0.04, 95 % CI: 0.04, 0.05, p < 0.001). The cost per quality-adjusted life year (QALY) gained was $12,893. ConclusionsOlder Australians who participated in the Exercise Right for Active Ageing programme reported small improvements in HRQoL following programme completion, and this included older adults living in regional/rural areas. Funding subsidised exercise classes, may be a low-cost strategy for improving health outcomes in older adults and reducing geographic health disparities. Clinical trial registrationThe study was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000483651).

Validity of the Active Australia Survey in an Australian cardiac rehabilitation population

ObjectivesTo examine the long-term validity of the Active Australia Survey in a cardiac rehabilitation population using accelerometry as the reference measure. DesignCohort validation study. MethodsCardiac rehabilitation participants with coronary heart disease were recruited to a prospective cohort study. Over 7-days, 61 participants wore an ActiGraph ActiSleep accelerometer (1-second epoch, 10-minute bout) and completed the self-administered Active Australia Survey at baseline, 6-weeks, 6 and 12-months. Total daily moderate-to-vigorous physical activity from both methods was compared using Bland-Altman plots and Spearman rank-order correlations. ResultsParticipants tended to over-report moderate-to-vigorous physical activity, with more active participants more likely to over-report moderate-to-vigorous physical activity. There was a good level of agreement between the accelerometer 1-second epochs and Active Australia Survey at all time points (mean bias (ratio) 1.04, 1.16, 1.14, and 1.06, respectively), with weak-moderate correlations (ρ = 0.3-0.48). Conversely, there was a poor level of agreement between the accelerometer 10-minute bouts and Active Australia Survey at all time points (mean bias (ratio) 6.78, 9.09, 6.35, and 5.68, respectively), with weak-moderate correlations (ρ = 0.3-0.52). Agreement between the two measures did not improve over time for both 1-second and 10-minute bout accelerometry data. ConclusionsThe Active Australia Survey may be an acceptable self-report measure of moderate-to-vigorous physical activity in cardiac rehabilitation attendees when capturing any time spent in moderate-to-vigorous physical activity. The Active Australia Survey may be useful to routinely monitor physical activity levels over-time in Australian cardiac rehabilitation programs at both individual and group levels. Trial registrationTrial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12615000995572, http://www.ANZCTR.org.au/ACTRN12615000995572.aspx.

Decentralised clinical trials in rural Australia: Opportunities and challenges

AbstractAimsTo present opportunities and a model to redress the under‐representation of rural communities and people in Australian clinical trials.ContextClinical trials are essential for building and understanding the health evidence base. The lack of representation of rural people in clinical trials is evident in other countries. Examining the Australian New Zealand Clinical Trial Registry (ANZCTR) suggests this is also the case in Australia.ApproachWe propose an approach that empowers rurally based academics and clinicians to co‐design clinical trials and increase rural Australians' participation in clinical trials to address this inequality of access. A case study of a decentralised, co‐designed clinical trial is presented to support this approach.ConclusionDecentralising clinical trials could improve access to clinical trials, strengthen the social capital of rural communities and help address the health inequalities that exist between rural and metropolitan communities.

Habitual consumption of anthocyanin is associated with improvements in mood and cognitive performance in older people with memory complaints

The role of flavonoids on cognitive performance in older adults has been intensively studied, with the subclass of anthocyanins showing promising outcomes(1). However, there is conflicting evidence in the case of individuals at high risk of developing dementia, namely those with mild cognitive impairment (MCI). A recent study has suggested that cognitive scores in people with MCI were higher in those who had higher anthocyanin intake (&gt;10 mg)(2). Baseline data from 65 participants of an ongoing clinical trial that had an MIS (Memory Index Score) score ≤ 13 with self-reported subjective memory complaints, (mean age 69.1y ± 6.2) were used to investigate the relationship between dietary anthocyanin intake and indices of mood and cognitive performance. Repeated 24-hour dietary intake was recorded through Intake24 (a computer-based program) for three days (2Xweekday and 1Xweekend day) and anthocyanin intake was quantified using the PhenolExplorer food composition database. The primary outcome of interest was the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall (FCSRT+IR) (assesses auditory anterograde memory functioning), while other cognitive functions assessed included: Spot the Word-2 (assessing premorbid estimate); Oral Symbol Digit Test (speed of processing); List Sorting (working memory); Trail Making Test A &amp; B (speed of processing/executive function); and Verbal Fluency (language/semantic memory). Subjective memory complaints were assessed using the Memory Assessment Clinic-Q (MAC-Q) and mood was assessed using the Geriatric Depression Scale (GDS). Independent t-tests were used to compare differences in cognitive tasks and mood scores between high (&gt;10 mg/d) and low consumers of anthocyanins (&lt;10 mg/d). There was a trend for high anthocyanin consumers (n = 35, median = 44.87 (10.01, 177.83)) to score better on FCSRT-Delayed Free Recall scores (16.57 ± 3.74) compared to lower consumers (n = 30, median = 0.01 (0, 9.51)), (15.97 ± 0.18) with a mean difference (SE) of −1.06 (0.58) (p = 0.06) suggesting recall of 1.06 more words after a 20-30 minute delay. Higher consumers had a lower GDS score (1.77 ± 3.73) compared to lower consumers (3.73 ± 1.77), p = 0.01. Spot the word test scores (assesses premorbid verbal abilities using a robust lexical decision task) were higher for high anthocyanin consumers (53.06 ± 4.38) compared to lower consumers (50.40 ± 4.38), mean difference (SE) = −2.66 (1.10), p = 0.01, meaning participants with higher intake of dietary anthocyanin were able to point at 2.7 more real words than low consumers. Dietary consumption of anthocyanin in older adults with MIS is associated with beneficial effects on depressive scores and the ability to retrieve words. Further research is warranted to identify optimal dosage for recommended intake. This cross-sectional study used baseline data from a randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ANZCTR):12622000065796.

Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE): protocol for a helix-counterbalanced randomised controlled trial

IntroductionClinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia’s new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care.Methods and analysisThe Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level.DiscussionThe EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 — retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx.

Single-centre, randomised clinical trial of the immunomodulatory mechanisms of daily supplementation of palm tocotrienol-rich fraction in healthy human volunteers following influenza vaccination.

Vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), has been shown to have immune-enhancing activity. To date, only one dose of TRF (400 mg daily) has been tested in a clinical trial. The proposed study will evaluate the immune-enhancing activity effects of lower doses (200, 100 and 50 mg) in a clinical trial using an influenza vaccine as the immunological challenge. A single-centre, randomised, parallel, double-blinded, placebo-controlled clinical trial with balance allocation involving five arms will be conducted. The healthy volunteers recruited will be randomly assigned to one of the arms, and they will be asked to take the respective supplements (400 mg, 200 mg, 100 mg, 50 mg of TRF or placebo) daily with their dinner. The volunteers will receive the influenza vaccine after four weeks. They will be asked to return to the study site four weeks later. A blood sample will be taken for the study at baseline, four and eight weeks. Primary outcome measures will be antibody levels to influenza, blood leucocyte profile and cytokine production. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns. The findings from this study will be published in relevant peer-reviewed journals and presented at relevant national and international scientific meetings. The recent world events have created the awareness of having a healthy and functional immune system. Nutrition plays an important role in helping the immune system to function optimally. This study will show the effects of lower doses of TRF in boosting the immune response of healthy individuals and also elucidate the mechanisms through which TRF exerts its immune-enhancing effects. Australian New Zealand Clinical Trials Registry (ANZCTR) [ ACTRN12622000844741] dated 15 June 2022. 2.

Harti Hauora Tamariki: randomised controlled trial protocol for an opportunistic, holistic and family centred approach to improving outcomes for hospitalised children and their families in Aotearoa, New Zealand.

Health and wellbeing inequities between the Indigenous Māori and non-Māori populations in Aotearoa, New Zealand continue to be unresolved. Within this context, and of particular concern, hospitalisations for diseases of poverty are increasing for tamariki Māori (Māori children). To provide hospitalised tamariki Māori, and their whānau (families) comprehensive support, a wellbeing needs assessment; the Harti Hauora Tamariki Tool (The Harti tool) was developed. The purpose of this study is to determine how effective the Harti tool is at identifying wellbeing needs, ensuring the documentation of needs, enabling access to services and improving wellbeing outcomes for tamariki and their whānau. The study uses a Kaupapa Māori methodology with qualitative and quantitative methods. Qualitative methods include in-depth interviews with whānau. This paper presents an overview of a randomised, two parallel, controlled, single blinded, superiority trial for quantitative evaluation of the Harti programme, and hospital satisfaction with care survey. Participants will be Māori and non-Māori tamariki/children aged 0-4 years admitted acutely to the paediatric medical wards at Waikato Hospital, Hamilton, Aotearoa New Zealand. They will be randomised electronically into the intervention or usual care group. The intervention group will receive usual care in addition to the Harti programme, which includes a 24-section health needs assessment delivered by trained Māori navigators to whānau during the time they are in hospital. The primary endpoint is the relative risk of an acute hospital readmission in the 30 days following discharge for the intervention group patients compared with control group patients. Secondary outcomes include access and utilisation of preventative health services including: oral health care, general practice enrolment, immunisation, healthy home initiatives, smoking cessation and the Well Child Tamariki Ora universal health checks available free of charge for children in Aotearoa New Zealand. Randomised controlled trials are a gold standard for measuring efficacy of complex multifaceted interventions and the results will provide high quality evidence for implementing the intervention nationwide. We expect that this study will provide valuable evidence for health services and policy makers who are considering how to improve the configuration of paediatric hospital services. The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number: ACTRN12618001079235.