Human Research Ethics Committee Approval Research Articles

Development of a microcosting protocol to determine the economic cost of diagnostic genomic testing for rare diseases in Australia

IntroductionGenomic testing is a relatively new, disruptive and complex health technology with multiple clinical applications in rare diseases, cancer and infection control. Genomic testing is increasingly being implemented into clinical...

Pre-gerotal fat patch-A novel alternative to haemostatic agents during partial nephrectomy.

This study aimed to determine if using a pre-gerotal fat patch at open partial nephrectomy (PN) as a haemostatic bolster is a viable alternative to using synthetic haemostatic agents. Human Research Ethics Committee approval was obtained for audit of a prospectively kept database from July 2012 to July 2021, which followed outcomes of patients who received a low-tension pre-gerotal fat patch renorrhaphy at open PN. Patient demographics, intraoperative measures, histological outcomes and post-operative complications were analysed. Using a retroperitoneal approach, the peritoneum was mobilised and a vascularised pedicle of pre-gerotal fat was rotated in the direction of the kidney. Routine definition of the hilum, clamping of the hilar vessels and dissection of mass followed. After watertight closure and haemostasis, the harvested pre-gerotal fat patch was placed over the defect and secured using low-tension renorrhaphy. Two-layer closure of the abdominal wall with placement of a drain was routine. A total of 55 patients underwent open PN. Mean age was 60.4 (35-77) years. There were 38 men and 17 women, and 32 right and 23 left PNs. Mean mass size was 31.9 mm (10-95 mm) and collecting system was breached in 36.5% of cases. One patient (1.9%) suffered a Clavien-Dindo IIIb complication requiring return to theatre and transfusion due to a bleed from an intercostal artery. There were no renal bed bleeds, urine leaks or urine fistulas detected. Mean intraoperative blood loss was 355 mL (50-1500 mL) and mean post-operative creatinine increased by 10.7 μmol/L (51-172 μmol/L). Mean follow up was 40.2 (4-109) months. Utilisation of an anatomical pre-gerotal fat patch to provide pressure at the renorrhaphy site during open PN is an effective technique to assist with surgical haemostasis. This simple technique avoids the costs of haemostatic agents, whilst adding minimal operating time to procedures.

Study protocol for development of an options assessment toolkit (OAT) for national malaria programs in Asia Pacific to determine best combinations of vivax radical cure for their given contexts.

Recent advances in G6PD deficiency screening and treatment are rapidly changing the landscape of radical cure of vivax malaria available for National Malaria Programs (NMPs). While NMPs await the WHO's global policy guidance on these advances, they will also need to consider different contextual factors related to the vivax burden, health system capacity, and resources available to support changes to their policies and practices. Therefore, we aim to develop an Options Assessment Toolkit (OAT) that enables NMPs to systematically determine optimal radical cure options for their given environments and potentially reduce decision-making delays. This protocol outlines the OAT development process. Utilizing participatory research methods, the OAT will be developed in four phases where the NMPs and experts will have active roles in designing the research process and the toolkit. In the first phase, an essential list of epidemiological, health system, and political & economic factors will be identified. In the second phase, 2-3 NMPs will be consulted to determine the relative priority and measurability of these factors. These factors and their threshold criteria will be validated with experts using a modified e-Delphi approach. In addition, 4-5 scenarios representing country contexts in the Asia Pacific region will be developed to obtain the expert-recommended radical cure options for each scenario. In the third phase, additional components of OAT, such as policy evaluation criteria, latest information on new radical cure options, and others, will be finalized. The OAT will be pilot-tested with other Asia Pacific NMPs in the final phase. Human Research Ethics Committee approval has been received from the Northern Territory, Department of Health, and Menzies School of Health Research (HREC Reference Number: 2022-4245). The OAT will be made available for the NMPs, introduced at the APMEN Vivax Working Group annual meeting, and reported in international journals.

High continuous positive airway pressures versus non-invasive positive pressure ventilation in preterm neonates: protocol for a multicentre pilot randomised controlled trial

IntroductionLow pressure nasal continuous positive airway pressure (nCPAP) has long been the mainstay of non-invasive respiratory support for preterm neonates, at a constant distending pressure of 5–8 cmH2O. When traditional...

Clinical practice guideline adherence in oncology: A qualitative study of insights from clinicians in Australia.

The burden of cancer is large in Australia, and rates of cancer Clinical Practice Guideline (CPG) adherence is suboptimal across various cancers. The objective of this study is to characterise clinician-perceived barriers and facilitators to cancer CPG adherence in Australia. Semi-structured interviews were conducted to collect data from 33 oncology-focused clinicians (surgeons, radiation oncologists, medical oncologists and haematologists). Clinicians were recruited in 2019 and 2020 through purposive and snowball sampling from 7 hospitals across Sydney, Australia, and interviewed either face-to-face in hospitals or by phone. Audio recordings were transcribed verbatim, and qualitative thematic analysis of the interview data was undertaken. Human research ethics committee approval and governance approval was granted (2019/ETH11722, #52019568810127). Five broad themes and subthemes of key barriers and facilitators to cancer treatment CPG adherence were identified: Theme 1: CPG content; Theme 2: Individual clinician and patient factors; Theme 3: Access to, awareness of and availability of CPGs; Theme 4: Organisational and cultural factors; and Theme 5: Development and implementation factors. The most frequently reported barriers to adherence were CPGs not catering for patient complexities, being slow to be updated, patient treatment preferences, geographical challenges for patients who travel large distances to access cancer services and limited funding of CPG recommended drugs. The most frequently reported facilitators to adherence were easy accessibility, peer review, multidisciplinary engagement or MDT attendance, and transparent CPG development by trusted, multidisciplinary experts. CPGs provide a reassuring framework for clinicians to check their treatment plans against. Clinicians want cancer CPGs to be frequently updated utilising a wiki-like process, and easily accessible online via a comprehensive database, coordinated by a well-trusted development body. Future implementation strategies of cancer CPGs in Australia should be tailored to consider these context-specific barriers and facilitators, taking into account both the content of CPGs and the communication of that content. The establishment of a centralised, comprehensive, online database, with living wiki-style cancer CPGs, coordinated by a well-funded development body, along with incorporation of recommendations into point-of-care decision support would potentially address many of the issues identified.

Using primary care data to understand opioid prescribing, policy impacts and clinical outcomes: A protocol for the OPPICO study.

Prescription opioid use in Australia has increased over the last 3 decades. The majority of opioids are prescribed and dispensed in primary care, however, there are few studies that are specific to opioid prescribing in this setting. Evidence about the impact of key government policy strategies to optimize opioid prescribing in primary care is limited. The aim of this study is to examine the impact of recent policy changes and clinical guidelines on opioid prescribing in primary care. Longitudinal analysis of people prescribed opioid analgesics using Population Level Analysis and Reporting (POLAR) data. POLAR is a primary care dataset comprising 464 primary health care practices in Victoria, Australia. People prescribed opioid analgesics between 2015 and 2020 will be included. The impact of opioid policies and guideline recommendations will be evaluated using interrupted time series models. Group- based trajectory modelling and multivariate regression will be used to identify patterns of opioid cessation and the provision of corresponding non-opioid interventions. The study has received Monash University Human Research Ethics Committee approval (ID 24139). Permission to access, collate and use POLAR data is granted from Outcome Health as the data custodians. The results of this study will be disseminated through publication in international journals, presented at national and international scientific conferences, and disseminated to consumers, policy makers, primary care providers and primary health networks. EU PAS Register (EUPAS43218).

Patient and Clinician Perspectives on the use of Remote Patient Monitoring in Peritoneal Dialysis.

Background:Numerous factors influence patient recruitment to, and retention on, peritoneal dialysis (PD), but a major challenge is a perceived “inaccessibility” to treating clinicians. It has been suggested that remote patient monitoring (RPM) could be a means of improving such oversight and, thereby, uptake of PD.Objective:To describe patient and clinician perspectives toward RPM and the use of applications (Apps) suitable for mobiles, tablets, or computers to support the provision of PD care.Design:Qualitative design using semi-structured interviews.Setting:All patient participants perform PD treatment at home under the oversight of an urban PD unit in Sydney, Australia. Patient and clinician interviews were conducted within the PD unit.Participants:14 participants (5 clinicians [2 nephrologists, 3 PD nurses] and 9 patients treated with PD).Methods:Semi-structured interviews were conducted using interview guides tailored for clinician and patient participants. Transcripts were coded and analyzed by a single researcher using thematic analysis.Results:Six themes were identified: perceived benefits of RPM implementation (offering convenience and efficiency, patient assurance through increased surveillance, more complete data and monitoring adherence), uncertainty regarding data governance (protection of personal data, data reliability), reduced patient engagement (transfer of responsibility leading to complacency), changing patient-clinician relationships (reduced patient-initiated communication, the need to maintain patient independence), increased patient and clinician burden (inadequate technological literacy, overmanagement leading to frequent treatment changes), and clinician preference influencing patient behavior.Limitations:The interviews were conducted in English only and with participants from a single urban dialysis unit, which may limit generalizability.Conclusions:For patients and clinicians, advantages from the use of RPM in PD may include increased patient confidence and assurance, improved treatment oversight, more complete data capture, and overcoming barriers to data documentation. Careful patient selection and patient and clinician education may help to optimize the benefits of RPM, maintain patient independence, and reduce the risks of patient disengagement. The use of an App may support RPM; however, participants expressed concerns about increasing the burden on some patients through the use of unfamiliar technology.Human Research Ethics Committee Approval Number:CH62/6/2019-028

Efficacy of Vaccine BNT162b2 (Pfizer-BioNTech) in Individuals with Waldenstrom's Macroglobulinemia and Follicular Lymphoma in Australia

IntroductionLymphoid malignancies are a risk factor for severe COVID-19. Vaccination with BNT162b2 protects the general population from severe disease, but recent studies have shown limited seroconversion after vaccination in patients with lymphoid malignancy. This reduced response is likely related to disease and treatment factors altering both humoral and cellular immunity. Assessing response in patients with the indolent lymphomas, Waldenström's Macroglobulinaemia (WM) and Follicular Lymphoma (FL), including cohorts on differing treatment regimens, may help elucidate some of these factors. Australia has had low prevalence of SARS-CoV-2 infection to date, affording a unique opportunity to assess efficacy to vaccination without the confounding impact of endemic infection.MethodsPatients with WM and FL and controls were enrolled in a prospective study of immune response after two doses of BNT162b2 administered 21 days apart. The study had Human Research Ethics Committee approval and all patients gave informed consent prior to participation. Recruitment was targeted to obtain comparable proportions of controls to treatment cohorts. PBMC and sera were collected from participants immediately prior to the first dose (T1), at day 21 immediately prior to the second dose (T2), and day 49 (+/- 7d) (T3). Immune response was measured by: flow cytometric detection of anti-SARS-CoV-2 spike antibodies (ASAb), performed using our recently validated flow cytometric live cell assay (Tea et.al. PLoS Medicine 2021) with increased sensitivity compared to currently available commercial ELISAs; live virus neutralisation to a panel of SARS-CoV-2 variants of concern; and CD4+and CD8+ antigen-specific T cell responses. Statistical analysis of medians between cohorts were compared by the Mann-Whitney non-parametric test using Graphpad Prism. Initial ASAb IgG data for T1 and T2 is presented here. Complete immune response data at all time points will be available for the ASH meeting.ResultsEighty-five participants received their first dose of BNT162b2 from 18 May 2021 to 7 June 2021 with a second dose 21 days later: 72 lymphoma patients (WM and FL) and 13 age-matched healthy volunteers (controls). Of 37 with WM [19 (51.3%) female, median 71 years (IQR 63-74)] 9 were treatment naïve (WMN), 15 had received rituximab-chemotherapy (WMT), and 13 were currently treated with a Bruton Tyrosine Kinase inhibitor (BTKi): 5 ibrutinib, 8 zanubrutinib (WMB). Of 35 patients with FL [16 (45.7%) female, median 65 years (IQR 54-71)], 11 were treatment naïve (FLN), and 24 had received rituximab-chemotherapy (FLT). Of the 13 controls 8 (61.5%) were female, median age 72 years (IQR 57-74)].No participants had detectable ASAb at T1, confirming no prior SARS-CoV-2 exposure. Figure 1 shows ASAb results at T2. The median mean fluorescence intensity (MFI) of healthy controls: 60802 (IQR 17565 -78443), is higher than all WM: 0 (IQR 0 - 15010) p<0.0001, and all FL patients: 1687 (IQR 0 - 25421) p=0.002, Fig 1A. The median MFI of controls was higher than WMN (p=0.036), but not higher than FLN (p=0.28). The median MFI of WMN: 20074 (IQR 5421 - 35695), is higher than WMB: 0 (IQR 0 - 4217) p=0.018, but not significantly higher than WMT: 0 (IQR 0 - 14356) p=0.13, Fig 1B. Median MFI of FLN: 31476 (IQR 19351 - 51317), is higher than FLT: 0 (IQR 0 - 32849) p=0.01, Fig 1B.ConclusionThese early serological data show measurable ASAb in all healthy controls 21 days post first dose of BNT162b2 vaccination. Treatment naïve patients had a better response than treated patients, and this did not differ significantly to healthy controls in the FL cohort. In WM, patients on BTKi had a significantly reduced response compared to treatment-naïve patients. This same reduction was not observed in the chemotherapy-rituximab cohort, but the characteristics of early responders versus non-responders, including time since last therapy, is being analysed. FL patients treated with chemotherapy-rituximab had a significantly reduced response compared to the treatment-naïve cohort.Time constraints before the abstract submission deadline prevented reporting of all mature vaccination response data. Measurement of ASAb one month after second vaccination, live virus neutralisation to a panel of SARS-CoV-2 variants of concern, and CD4+ and CD8+ antigen-specific T cell responses at T1, T2 and T3, to fully characterise the immune response to BNT162b2, will be reported at the ASH meeting. [Display omitted] DisclosuresRankin: Novo Nordisk Pharmaceuticals: Other: Travel reimbursement to attend haemophilia academy. Kelleher: CSL/Sequiris: Honoraria; Aegros and CSL: Consultancy; Merck: Speakers Bureau; Aegros, CSL, Merek: Membership on an entity's Board of Directors or advisory committees. Brilot: Novartis: Research Funding; Biogen, Merck: Honoraria. Trotman: beigene: Research Funding; roche: Research Funding; PCYC: Research Funding; BMS: Research Funding; TAKEDA: Research Funding; JANSSEN: Research Funding.

Effect of a physical activity and sleep m-health intervention on a composite activity-sleep behaviour score and mental health: a mediation analysis of two randomised controlled trials

BackgroundTo examine if a composite activity-sleep behaviour index (ASI) mediates the effects of a combined physical activity and sleep intervention on symptoms of depression, anxiety, or stress, quality of life (QOL), energy and fatigue in adults.MethodsThis analysis used data pooled from two studies: Synergy and Refresh. Synergy: Physically inactive adults (18–65 years) who reported poor sleep quality were recruited for a two-arm Randomised Controlled Trial (RCT) (Physical Activity and Sleep Health (PAS; n = 80), or Wait-list Control (CON; n = 80) groups). Refresh: Physically inactive adults (40–65 years) who reported poor sleep quality were recruited for a three-arm RCT (PAS (n = 110), Sleep Health-Only (SO; n = 110) or CON (n = 55) groups). The SO group was omitted from this study. The PAS groups received a pedometer, and accessed a smartphone/tablet “app” using behaviour change strategies (e.g., self-monitoring, goal setting, action planning), with additional email/SMS support. The ASI score comprised self-reported moderate-to-vigorous-intensity physical activity, resistance training, sitting time, sleep duration, efficiency, quality and timing. Outcomes were assessed using DASS-21 (depression, anxiety, stress), SF-12 (QOL-physical, QOL-mental) and SF-36 (Energy & Fatigue). Assessments were conducted at baseline, 3 months (primary time-point), and 6 months. Mediation effects were examined using Structural Equation Modelling and the product of coefficients approach (AB), with significance set at 0.05.ResultsAt 3 months there were no direct intervention effects on mental health, QOL or energy and fatigue (all p > 0.05), and the intervention significantly improved the ASI (all p < 0.05). A more favourable ASI score was associated with improved symptoms of depression, anxiety, stress, QOL-mental and of energy and fatigue (all p < 0.05). The intervention effects on symptoms of depression ([AB; 95%CI] -0.31; − 0.60,-0.11), anxiety (− 0.11; − 0.27,-0.01), stress (− 0.37; − 0.65,-0.174), QOL-mental (0.53; 0.22, 1.01) and ratings of energy and fatigue (0.85; 0.33, 1.63) were mediated by ASI. At 6 months the magnitude of association was larger although the overall pattern of results remained similar.ConclusionsImprovements in the overall physical activity and sleep behaviours of adults partially mediated the intervention effects on mental health and quality of life outcomes. This highlights the potential benefit of improving the overall pattern of physical activity and sleep on these outcomes.Trial registrationAustralian New Zealand Clinical Trial Registry: ACTRN12617000680369; ACTRN12617000376347.Universal Trial number: U1111–1194-2680; U1111–1186-6588. Human Research Ethics Committee Approval: H-2016-0267; H-2016–0181.

Development of an &lt;i&gt; in-situ&lt;/i&gt; Printing System with Human Platelet Lysate Based Bioink to Treat Corneal Perforation

Purpose: Corneal perforation is a clinical emergency. Tissue glue to seal the perforation, and supplementary topical medication represents existing standard treatment. Previously, our group developed a transparent bioink that showed good cell compatibility and accelerated corneal epithelial cells healing in-vitro. This study aims to develop a novel treatment method for corneal perforation using this bioink. Methods: Rheometry was used to measure bioink behaviour at room and corneal surface temperatures. Bioink adhesiveness to porcine skin and burst pressure limit were also measured. Based on rheological behaviour, a hand-held biopen was developed to extrude the bioink onto the cornea. An animal trial (5 New Zealand white rabbits) to compare bioink and cyanoacrylate glue (control group) impact on a 2mm perforation was conducted to evaluate safety and efficacy. Results: Bioink has higher adhesiveness compared to commercial fibrin glue and can withstand burst pressure approximately 6.4x higher than routine intraocular pressure. Bioink-treated rabbits had lower pain score and faster recovery, despite generating similar scar-forming structure after healing compared to controls. No secondary corneal ulcer was generated in rabbits treated with bioink. Conclusions: This study reports a novel in-situ printing system capable of delivering a transparent bioink to the cornea and successfully treating small corneal perforations. Bioink-treated rabbits recovered faster to completely healed perforation and required no additional analgesia. Both groups showed scarred corneal tissue after healing, however no infection and inflammation was observed 3 weeks. The delivery system was easy to use and may represent an alternative treatment for corneal perforation. Funding Information: We acknowledge the funding support from Australian Research Council (ARC) Centre of Excellence Scheme (CE140100012), Sydney Eye Hospital Foundation and NSW Medical Device Fund. The hPL used within the study was a gift from Australia Red Cross. Declaration of Interests: J. You (P), iFix Medical (I,F); H. Frazer (P); S. Sayyar, None; Z. Chen, None; X. Liu, None; A. Taylor, None; B. Filippi, None; S. Beirne, None; I. Wise, None; C. Hodge, None; G. Wallace, None; G. Sutton (P), iFix Medical (I). Ethics Approval Statement: Human corneas not meeting transplantation quality requirements were obtained from New South Wales Organ & Tissue Donation Service (Human Research Ethics Committee approval 14/275). The trial was conducted at the University of Sydney Charles Perkins Centre Laboratory Animal House Facility with Animal Ethics Committee approval (AEC: 2018/1317).

The Impact of a Novel Mimicry Task for Increasing Emotion Recognition in Adults with Autism Spectrum Disorder and Alexithymia: Protocol for a Randomized Controlled Trial.

BackgroundImpaired facial emotion expression recognition (FEER) has typically been considered a correlate of autism spectrum disorder (ASD). Now, the alexithymia hypothesis is suggesting that this emotion processing problem is instead related to alexithymia, which frequently co-occurs with ASD. By combining predictive coding theories of ASD and simulation theories of emotion recognition, it is suggested that facial mimicry may improve the training of FEER in ASD and alexithymia.ObjectiveThis study aims to evaluate a novel mimicry task to improve FEER in adults with and without ASD and alexithymia. Additionally, this study will aim to determine the contributions of alexithymia and ASD to FEER ability and assess which of these 2 populations benefit from this training task.MethodsRecruitment will primarily take place through an ASD community group with emphasis put on snowball recruiting. Included will be 64 consenting adults equally divided between participants without an ASD and participants with an ASD. Participants will be screened online using the Kessler Psychological Distress Scale (K-10; cut-off score of 22), Autism Spectrum Quotient (AQ-10), and Toronto Alexithymia Scale (TAS-20) followed by a clinical interview with a provisional psychologist at the Federation University psychology clinic. The clinical interview will include assessment of ability, anxiety, and depression as well as discussion of past ASD diagnosis and confirmatory administration of the Autism Mental Status Exam (AMSE). Following the clinical interview, the participant will complete the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and then undertake a baseline assessment of FEER. Consenting participants will then be assigned using a permuted blocked randomization method into either the control task condition or the mimicry task condition. A brief measure of satisfaction of the task and a debriefing session will conclude the study.ResultsThe study has Federation University Human Research Ethics Committee approval and is registered with the Australian New Zealand Clinical Trials. Participant recruitment is predicted to begin in the third quarter of 2021.ConclusionsThis study will be the first to evaluate the use of a novel facial mimicry task condition to increase FEER in adults with ASD and alexithymia. If efficacious, this task could prove useful as a cost-effective adjunct intervention that could be used at home and thus remove barriers to entry. This study will also explore the unique effectiveness of this task in people without an ASD, with an ASD, and with alexithymia.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12619000705189p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377455International Registered Report Identifier (IRRID)PRR1-10.2196/24543

Bridging the gap between physical and mental illness in community pharmacy (PharMIbridge): protocol for an Australian cluster randomised controlled trial

IntroductionThere is a significant life expectancy gap attributable to physical comorbidities for people living with severe and persistent mental illness (SPMI) compared with the general population. Medications are a major...

10kHz spinal cord stimulation for chronic upper limb and neck pain: Australian experience.

Intractable upper limb and neck pain has traditionally been a challenging pain condition to treat, with conventional spinal cord stimulation (SCS) often inducing positional variation in paraesthesia and/or inadequate coverage of axial neck pain. The purpose of this Australian multi-centre prospective, clinical trial was to assess the safety and effectiveness of paraesthesia-independent 10kHz SCS for the treatment of upper limb and neck pain. Subjects with chronic, intractable neck and/or upper limb pain of ≥ 5cm (on a 0-10-cm visual analogue scale) were enrolled (ACTRN12614000153617) following human research ethics committee approval. Subjects were implanted with two epidural leads spanning C2-C6 vertebral bodies. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp., Redwood City, CA, USA) and included in the safety and effectiveness evaluation at 3 months post-implant (primary endpoint assessment, PEA) and followed to 12 months. Overall, 31/38 (82.6%) subjects reported a successful 10kHz SCS trial and proceeded to a permanent implant. Twenty-three of 30 subjects (76.7%) met the PEA. Subjects reported a reduction in neck pain and upper limb pain from baseline at the PEA (8.1 ± 0.2cm vs. 2.9 ± 0.5cm, 7.3 ± 0.3cm vs. 2.5 ± 0.5cm, respectively, p ≤ 0.0001). Disability, as measured by pain disability index score, decreased from 42.6 ± 2.6 at baseline to 22.7 ± 3.2 at PEA. Results were maintained 12 months post-implant. No neurological deficits, nor reports of paraesthesia, were observed. Stable, long-term results demonstrated that 10kHz SCS is a promising therapy option for intractable chronic upper limb and neck pain.

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients.

Background: A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field.Method: Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment.Results: One hundred and eight participants (mEHT: HIV-positive n = 25, HIV-negative n = 29; Control Group: HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group: n = 13 [24.1%] than the control group: n = 3 [5.6%] (Chi squared, Fisher's exact: p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group.Conclusion: The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease.

Abstract CT118: CARPETS: A Phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumors

Abstract Background: Chimeric antigen receptor (CAR) T cells are genetically engineered to recognize tumor-associated antigens and have potent cytolytic activity against tumors. Adoptive therapy with CAR-T cells has been highly successful in B-cell malignancies but is yet to demonstrate significant clinical benefit in patients with solid tumors. Currently, we are conducting the CARPETS study (ACTRN12613000198729 at www.anzctr.org.au), which is a phase I clinical trial of third-generation GD2-specific CAR-T cells in metastatic melanoma patients at the Royal Adelaide Hospital. This is a world-first trial using CAR T-cell therapy for melanoma and combines a single intravenous infusion of CAR-T cells with standard kinase inhibitor therapy. In vitro correlative studies support cytolytic targeting of melanoma cells by the GD2-CAR-T cells but the ex vivo analyses of study patients’ post-infusion peripheral blood samples indicate poor CAR-T cell expansion and persistence with evidence of an exhausted T-cell phenotype. Further in vitro developmental work has resulted in optimized CAR-T cell manufacturing conditions that now favour generation of GD2-CAR-T cells with a dominant memory phenotype, which may have greater potential for long-term persistence in vivo. Methods:This trial is open but not recruiting while we await Human Research Ethics Committee approval of a clinical protocol amendment, which is expected by March 2019. Currently, six patients have been recruited of a planned enrolment of 12 patients. Dose escalation has proceeded through three dose levels using a Bayesian continual reassessment method. No dose limiting toxicities were observed in the previously enrolled cohorts. Under the proposed protocol amendment, the remaining six patients will be recruited with eligibility broadened to include other adult GD2-positive malignancies such as bony and soft tissue sarcomas, small cell lung cancer, and triple negative breast cancer. In future correlative studies, the purpose of the additional patient recruitment will be to compare the in vivo expansion and persistence of GD2-CAR-T cells, which will now be manufactured to carry the favorable memory phenotype, with previously transferred GD2-CAR-T cells, the manufacture of which was associated with the unfavorable exhausted phenotype. Because of the potential risk of additional toxicity conferred by the altered ex vivo CAR-T cell manufacturing conditions, dose escalation will proceed from dose level 2 and lympho-depleting chemotherapy will not be given. The next data analysis will be related to completed dose escalation using CAR-T cell products manufactured according to the new conditions. Citation Format: Michael Brown, Tessa Gargett. CARPETS: A Phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT118.

Multi-centre ethics and research governance review can impede non-interventional clinical research.

The inter-jurisdictional National Mutual Acceptance (NMA) scheme for Human Research Ethics Committee (HREC) approvals of human research is designed to reduce the reported delays and costs of ethical review. Introduction of the NMA set forth an uncoupling of the ethics and governance review processes, permitting a single ethical review for multiple sites, while continuing separate governance review for each centre covering financial and operational aspects of the research project. To compare the time required to gain ethics and governance approvals in Australia for a non-interventional investigator-led study from December 2015 to approval times for an earlier pre-NMA study utilising a similar study design and study sites and evaluate the effect that the NMA has had on total approval time for non-interventional multi-centre projects. We recorded the time taken to obtain ethics and governance approval at 16 sites for our nationwide low-risk non-interventional study looking at the prevalence and aetiology of non-tuberculous mycobacterial infection in people with cystic fibrosis in Australia. Applications were submitted to three hospitals and one university HREC to conduct our study at 16 hospital sites, HREC approval took from 16 to 79 days (median 28). Subsequent site-specific governance approval at 15 hospital sites took 23-225 days (median 83). The entire process of gaining ethical and governance approval to conduct the study at 16 sites took 24 months at an estimated cost of AU$56000 (US$ 42 000). Lengthy governance approval processes negate benefits gained from centralised ethics review under the NMA.

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

IntroductionManual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective...

Intubation of a Paediatric Manikin in Tongue Oedema and Face-to-Face Simulations by Novice Personnel: a Comparison of Glidescope, Airtraq and Direct Laryngoscopy

Glidescope and Airtraq were designed for facilitating intubation and for teaching regarding the airway anatomy. We aimed to evaluate their efficacy in normal airway, tongue oedema and face-to-face orotracheal intubation models when used by novice personnel. After the local human research ethics committee approval, 36 medical students who were in the beginning of their third year were enrolled in this study. After watching a video regarding intubation using one of these devices, the students intubated a paediatric manikin with a Glidescope or Airtraq via the normal airway, tongue oedema and face-to-face approach. Although the insertion and intubation times were similar among the groups, the intubation success rate of the Glidescope was higher in the normal airway (100% vs 67%) and tongue oedema (89% vs. 50%) compared with the Airtraq (p=0.008 and p=0.009). The success rates with the paediatric manikin by the face-to-face approach were similar among the groups (50%) (p=0.7). The need for manoeuvres in the Glidescope was lower in the normal and tongue oedema models (p=0.02 and p=0.002). In addition, oesophageal intubation was low in the control and tongue oedema models with the Glidescope (p=0.03 and p<0.001). Novice personnel could more easily intubate the trachea with the Glidescope than with the Airtraq. Intubation with the Glidescope was superior to that with the Airtraq in the normal and tongue oedema models. The face-to-face intubation success rates were both low with both the Glidescope and Airtraq groups.

Why should ethics approval be required prior to publication of health promotion research?

Most academic journals that publish studies involving human participants require evidence that the research has been approved by a human research ethics committee (HREC). Yet journals continue to receive submissions from authors who have failed to obtain such approval. In this paper, we provide an ethical justification of why journals should not, in general, publish articles describing research that has no ethics approval, with particular attention to the health promotion context. Using theoretical bioethical reasoning and drawing on a case study, we first rebut some potential criticisms of the need for research ethics approval. We then outline four positive claims to justify a presumption that research should, in most instances, be published only if it has been undertaken with HREC approval. We present four justifications for requiring ethics approval before publication: (1) HREC approval adds legitimacy to the research; (2) the process of obtaining HREC approval can improve the quality of an intervention being investigated; (3) obtaining HREC approval can help mitigate harm; and (4) obtaining HREC approval demonstrates respect for persons. This paper provides a systematic and comprehensive assessment of why research ethics approval should generally be obtained before publishing in the health promotion context. So what? Journals such as the Health Promotion Journal of Australia have recently begun to require research ethics approval for publishing research. Health promotion researchers will be interested in learning the ethical justification for this change.

Data linkage capabilities in Australia: practical issues identified by a Population Health Research Network ‘Proof of Concept project’

Objective:To describe the practical issues that need to be overcome to conduct national data linkage projects in Australia and propose recommendations to improve efficiency. Methods:Review of the processes, documentation and applications required to conduct national data linkage in Australia. Results:The establishment of state and national data linkage centres in Australia has placed Australia at the forefront of research linking health‐related administrative data collections. However, improvements are needed to reduce the clerical burden on researchers, simplify the process of obtaining ethics approval, improve data accessibility, and thus improve the efficiency of data linkage research. Conclusions:While a sound state and national data linkage infrastructure is in place, the current complexity, duplication and lack of cohesion undermines any attempts to conduct research involving national record linkage in a timely manner. Implications:Data linkage applications and Human Research Ethics Committee approval processes need to be streamlined and duplication removed, in order to reduce the administrative and financial burden on researchers if national data linkage research is to be viable.