Protocol for a bandit-based response adaptive trial to evaluate the effectiveness of brief self-guided digital interventions for reducing psychological distress in university students: the Vibe Up study.

INTRODUCTION: Meta-analytical evidence confirms a range of interventions, including mindfulness, physical activity and sleep hygiene, can reduce psychological distress in university students. However, it is unclear which intervention is most effective. Artificial intelligence (AI)-driven adaptive trials may be an efficient method to determine what works best and for whom. The primary purpose of the study is to rank the effectiveness of mindfulness, physical activity, sleep hygiene and an active control on reducing distress, using a multiarm contextual bandit-based AI-adaptive trial method. Furthermore, the study will explore which interventions have the largest effect for students with different levels of baseline distress severity. METHODS AND ANALYSIS: The Vibe Up study is a pragmatically oriented, decentralised AI-adaptive group sequential randomised controlled trial comparing the effectiveness of one of three brief, 2-week digital self-guided interventions (mindfulness, physical activity or sleep hygiene) or active control (ecological momentary assessment) in reducing self-reported psychological distress in Australian university students. The adaptive trial methodology involves up to 12 sequential mini-trials that allow for the optimisation of allocation ratios. The primary outcome is change in psychological distress (Depression, Anxiety and Stress Scale, 21-item version, DASS-21 total score) from preintervention to postintervention. Secondary outcomes include change in physical activity, sleep quality and mindfulness from preintervention to postintervention. Planned contrasts will compare the four groups (ie, the three intervention and control) using self-reported psychological distress at prespecified time points for interim analyses. The study aims to determine the best performing intervention, as well as ranking of other interventions. ETHICS AND DISSEMINATION: Ethical approval was sought and obtained from the UNSW Sydney Human Research Ethics Committee (HREC A, HC200466). A trial protocol adhering to the requirements of the Guideline for Good Clinical Practice was prepared for and approved by the Sponsor, UNSW Sydney (Protocol number: HC200466_CTP). TRIAL REGISTRATION NUMBER: ACTRN12621001223820.

Economic evaluation protocol for a multicentre randomised controlled trial to compare Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) versus usual care cardiac rehabilitation among people with coronary heart disease.

INTRODUCTION: It is important to ascertain the cost-effectiveness of alternative services to traditional cardiac rehabilitation while the economic credentials of the Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) programme among people with coronary heart disease (CHD) are unknown. This economic protocol outlines the methods for undertaking a trial-based economic evaluation of SCRAM in the real-world setting in Australia. METHODS AND ANALYSIS: The within-trial economic evaluation will be undertaken alongside a randomised controlled trial (RCT) designed to determine the effectiveness of SCRAM in comparison with the usual care cardiac rehabilitation (UC) alone in people with CHD. Pathway analysis will be performed to identify all the costs related to the delivery of SCRAM and UC. Both a healthcare system and a limited societal perspective will be adopted to gauge all costs associated with health resource utilisation and productivity loss. Healthcare resource use over the 6-month participation period will be extracted from administrative databases (ie, Pharmaceutical Benefits Scheme and Medical Benefits Schedule). Productivity loss will be measured by absenteeism from work (valued by human capital approach). The primary outcomes for the economic evaluation are maximal oxygen uptake (VO2max, mL/kg/min, primary RCT outcome) and quality-adjusted life years estimated from health-related quality of life as assessed by the Assessment of Quality of Life-8D instrument. The incremental cost-effectiveness ratio will be calculated using the differences in costs and benefits (ie, primary and secondary outcomes) between the two randomised groups from both perspectives with no discounting. All costs will be valued in Australian dollars for year 2020. ETHICS AND DISSEMINATION: The study protocol has been approved under Australia's National Mutual Acceptance agreement by the Melbourne Health Human Research Ethics Committee (HREC/18/MH/119). It is anticipated that SCRAM is a cost-effective cardiac telerehabilitation programme for people with CHD from both a healthcare and a limited societal perspective in Australia. The evaluation will provide evidence to underpin national scale-up of the programme to a wider population. The results of the economic analysis will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12618001458224).

Smartphone Cardiac Rehabilitation, Assisted Self-Management Versus Usual Care: Protocol for a Multicenter Randomized Controlled Trial to Compare Effects and Costs Among People With Coronary Heart Disease.

BACKGROUND: Alternative evidence-based cardiac rehabilitation (CR) delivery models that overcome significant barriers to access and delivery are needed to address persistent low utilization. Models utilizing contemporary digital technologies could significantly improve reach and fidelity as complementary alternatives to traditional center-based programs. OBJECTIVE: The aim of this study is to compare the effects and costs of the innovative Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) intervention with usual care CR. METHODS: In this investigator-, assessor-, and statistician-blinded parallel 2-arm randomized controlled trial, 220 adults (18+ years) with coronary heart disease are being recruited from 3 hospitals in metropolitan and regional Victoria, Australia. Participants are randomized (1:1) to receive advice to engage with usual care CR or the SCRAM intervention. SCRAM is a 24-week dual-phase intervention that includes 12 weeks of real-time remote exercise supervision and coaching from exercise physiologists, which is followed by 12 weeks of data-driven nonreal-time remote coaching via telephone. Both intervention phases include evidence- and theory-based multifactorial behavior change support delivered via smartphone push notifications. Outcomes assessed at baseline, 12 weeks, and 24 weeks include maximal aerobic exercise capacity (primary outcome at 24 weeks), modifiable cardiovascular risk factors, exercise adherence, secondary prevention self-management behaviors, health-related quality of life, and adverse events. Economic and process evaluations will determine cost-effectiveness and participant perceptions of the treatment arms, respectively. RESULTS: The trial was funded in November 2017 and received ethical approval in June 2018. Recruitment began in November 2018. As of September 2019, 54 participants have been randomized into the trial. CONCLUSIONS: The innovative multiphase SCRAM intervention delivers real-time remote exercise supervision and evidence-based self-management behavioral support to participants, regardless of their geographic proximity to traditional center-based CR facilities. Our trial will provide unique and valuable information about effects of SCRAM on outcomes associated with cardiac and all-cause mortality, as well as acceptability and cost-effectiveness. These findings will be important to inform health care providers about the potential for innovative program delivery models, such as SCRAM, to be implemented at scale, as a complement to existing CR programs. The inclusion of a cohort comprising metropolitan-, regional-, and rural-dwelling participants will help to understand the role of this delivery model across health care contexts with diverse needs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12618001458224; anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374508. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15022.

Cercariform cells: another cytologic feature distinguishing solid pseudopapillary neoplasms from pancreatic endocrine neoplasms and acinar cell carcinomas in endoscopic ultrasound-guided fine-needle aspirates.

BACKGROUND: Solid pseudopapillary neoplasm (SPPN) is a rare tumor of unknown origin that occurs predominantly in the body or tail of the pancreas in young women. The authors recently identified cercariform (Greek: tailed) cells, similar to those described in urothelial carcinomas, as a consistent cytologic feature in ultrasound-guided fine-needle aspiration (EUS-FNA) samples from SPPNs. The objective of the current multi-institutional study was to define the value of these cells in the differential diagnosis of SPPN with other neoplasms characterized cytologically by the presence of monotonous, uniform cells in pancreatic aspirates: pancreatic neuroendocrine tumors (Pan-NETs) and acinar cell carcinomas (ACCs). METHODS: The files of 4 academic hospitals were searched for SPPNs, Pan-NETs, and ACCs that were diagnosed by EUS-FNA. The slides were reviewed, and several cytologic features were recorded semiquantitatively to identify discriminating features between SPPNs, Pan-NETs, and ACCs. RESULTS: From the analysis of 18 SPPNs, 4 ACCs, and 20 Pan-NETs, the following cytologic features were identified as common to all 3 neoplasms: single cells and rosettes/acinar cell groups, round-to-plasmacytoid cells, pale-to-granular cytoplasm, fine vacuoles, and binucleated cells. Papillary structures, cercariform cells, large cytoplasmic vacuoles, reniform nuclei, hyaline globules/magenta-colored material, and degenerative features (cholesterol crystals, calcifications, foam cells, or giant cells) were significantly more common in SPPNs. Prominent nuclear grooves were encountered in only 4 of 18 SPPNs. CONCLUSIONS: The current results indicated that the presence of cercariform cells is another useful clue for the cytologic diagnosis of SPPN in challenging cases.

The flow fields involved in hydrodynamic imaging by blind Mexican cave fish (Astyanax fasciatus). Part I: open water and heading towards a wall.

Blind Mexican cave fish (Astyanax fasciatus) sense the presence of nearby objects by sensing changes in the water flow around their body. The information available to the fish using this hydrodynamic imaging ability depends on the properties of the flow field it generates while gliding and how this flow field is altered by the presence of objects. Here, we used particle image velocimetry to measure the flow fields around gliding blind cave fish as they moved through open water and when heading towards a wall. These measurements, combined with computational fluid dynamics models, were used to estimate the stimulus to the lateral line system of the fish. Our results showed that there was a high-pressure region around the nose of the fish, low-pressure regions corresponding to accelerated flow around the widest part of the body and a thick laminar boundary layer down the body. When approaching a wall head-on, the changes in the stimulus to the lateral line were confined to approximately the first 20% of the body. Assuming that the fish are sensitive to a certain relative change in lateral line stimuli, it was found that swimming at higher Reynolds numbers slightly decreased the distance at which the fish could detect a wall when approaching head-on, which is the opposite to what has previously been expected. However, when the effects of environmental noise are considered, swimming at higher speed may improve the signal to noise ratio of the stimulus to the lateral line.

The flow fields involved in hydrodynamic imaging by blind Mexican cave fish (Astyanax fasciatus). Part II: gliding parallel to a wall.

Blind Mexican cave fish (Astyanax fasciatus) are able to sense detailed information about objects by gliding alongside them and sensing changes in the flow field around their body using their lateral line sensory system. Hence the fish are able to build hydrodynamic images of their surroundings. This study measured the flow fields around blind cave fish using particle image velocimetry (PIV) as they swam parallel to a wall. Computational fluid dynamics models were also used to calculate the flow fields and the stimuli to the lateral line sensory system. Our results showed that characteristic changes in the form of the flow field occurred when the fish were within approximately 0.20 body lengths (BL) of a wall. The magnitude of these changes increased steadily as the distance between the fish and the wall was reduced. When the fish were within 0.02 BL of the wall there was a change in the form of the flow field owing to the merging of the boundary layers on the body of the fish and the wall. The stimuli to the lateral line appears to be sufficient for fish to detect walls when they are 0.10 BL away (the mean distance at which they normally swim from a wall), but insufficient for the fish to detect a wall when 0.25 BL away. This suggests that the nature of the flow fields surrounding the fish are such that hydrodynamic imaging can only be used by fish to detect surfaces at short range.

Time trends in fungal infections as a cause of death in hematopoietic stem cell transplant recipients: an autopsy study.

Infectious complications remain an important cause of death in hematopoietic stem cell transplant (HSCT) recipients. We undertook a 20-year (1988-2007) retrospective review of all autopsies performed on HSCT recipients in our institution, with emphasis on infections, especially fungal infections, as the cause of death. Of the 2,943 autopsies performed in our institution from 1988 to 2007, 395 (13.4%) involved HSCT recipients (117 pediatric; 278 adult). Of the patients, 298 had received allogeneic, 46 autologous, 41 umbilical cord blood, and 3 autologous plus allogeneic types, and 7 were unknown HSCT types. The most common causes of death were pulmonary complications, occurring in 247 (62.5%) of 395 cases. In 178 cases (45.1%), microorganisms (viral, bacterial, and/or fungal) were documented at autopsy in one or more organs and contributed to the cause of death. Fungal infections were found in 23.5% of cases, but their frequency as a cause of death decreased throughout this study, from 30.3% in the 1988-1992 period to 10.9% in the 2003-2007 period.

Cytology of metastatic thymic well-differentiated neuroendocrine carcinoma (thymic carcinoid) in pleural fluid: report of a case.

Thymic carcinoid tumors (well-differentiated neuroendocrine carcinomas) are uncommon anterior mediastinal neoplasms. These tumors are frequently accompanied by other endocrinopathies as part of a multiple endocrine neoplasia type I syndrome (MEN type I) and by paraneoplastic Cushing's syndrome and have a poor prognosis. We present the case of a 24-year-old man who presented for follow-up of thymic carcinoid with extensive bony metastases. He had recently completed radiotherapy to lesions involving his skull and mandible. An ultrasound-guided left-sided diagnostic and therapeutic thoracentesis was performed yielding 1 l of cloudy yellow fluid. The cytologic fluid preparations consisted of large "cannonballs" and atypical cell groups with salt and pepper nuclear chromatin. A panel of immunohistochemical stains were performed on the cell block material, and the atypical cells were positive for cytokeratin, synaptophysin, and chromogranin, but not for TTF1. These findings were consistent with metastatic well-differentiated neuroendocrine carcinoma (carcinoid tumor). This is the first reported case of a carcinoid tumor manifesting as large, spherical, smoothly contoured cell aggregates ("cannonballs") in a pleural fluid. Despite its rarity, a metastatic carcinoid tumor should be considered when "cannonballs" are found in effusions.

Design and synthesis of a diverse morpholine template library.

Efficient and general procedures have been developed for the solution-phase preparation of substituted morpholine derivatives, and a library has been produced around generic structure 1. This library was designed with proprietary modeling software for use as a general screening library. The 30 R1 reagents were phenols, and the 275 R2 reagents were taken from five different reagent classes, giving a variety of product classes in the final library of 8250 potential products. All of the library members were generated from a common intermediate, mesylate (5), which was synthesized efficiently, in bulk, in three steps from N-benzylethanolamine (2). High-throughput chemistry using robotics was carried out to produce the 7907 library members, which were individually characterized by reversed-phase LC/MS analysis.