Smartphone application for preventing depression: Study protocol for a workplace randomised controlled trial

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Depression is the leading cause of life years lost due to disability. Appropriate prevention has the potential to reduce the incidence of new cases of depression, however, traditional prevention approaches face significant scalability issues. Prevention programmes delivered by via smartphone applications provide a potential solution. The workplace is an ideal setting to roll out this form of intervention, particularly among industries that are unlikely to access traditional health initiatives and whose workplace characteristics create accessibility and portability issues. The study aims to evaluate the effectiveness of a smartphone application designed to prevent depression and improve well-being. The effectiveness of the app as a universal, selective and indicated prevention tool will also be evaluated. Methods and analysis A multicentre randomised controlled trial, to determine the effectiveness of the intervention compared with an active mood monitoring control in reducing depressive symptoms (primary outcome) and the prevalence of depression at 3 months, with secondary outcomes assessing well-being and work performance. Employees from a range of industries will be invited to participate. Participants with likely current depression at baseline will be excluded. Following baseline assessment, participants, blinded to their allocation, will be randomised to receive one of two versions of the application: headgear (a 30-day mental health intervention) or a control application (mood monitoring for 30 days). Both versions of the app contain a risk calculator to provide a measure of future risk. Analyses will be conducted within an intention-To-Treat framework using mixed modelling, with additional analyses conducted to compare the moderating effect of baseline risk level and depression symptom severity on the intervention's effectiveness. Ethics and dissemination The current trial has received ethics approval from the University of New South Wales Human Research Ethics Committee (HC17021). Study results will be disseminated through peer-reviewed journals and conferences. Trial registration number ACTRN12617000548336; Results

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Preventing depression using a smartphone app: a randomized controlled trial

Background There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers. Methods A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling. Results Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26–0.70). Conclusions This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition. Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN1261700054833

A smartphone application for treating depressive symptoms: study protocol for a randomised controlled trial.

BACKGROUND: Depression is a commonly occurring disorder linked to diminished role functioning and quality of life. The development of treatments that overcome barriers to accessing treatment remains an important area of clinical research as most people delay or do not receive treatment at an appropriate time. The workplace is an ideal setting to roll-out an intervention, particularly given the substantial psychological benefits associated with remaining in the workforce. Mobile health (mhealth) interventions utilising smartphone applications (apps) offer novel solutions to disseminating evidence based programs, however few apps have undergone rigorous testing. The present study aims to evaluate the effectiveness of a smartphone app designed to treat depressive symptoms in workers. METHODS: The present study is a multicentre randomised controlled trial (RCT), comparing the effectiveness of the intervention to that of an attention control. The primary outcome measured will be reduced depressive symptoms at 3 months. Secondary outcomes such as wellbeing and work performance will also be measured. Employees from a range of industries will be recruited via a mixture of targeted social media advertising and Industry partners. Participants will be included if they present with likely current depression at baseline. Following baseline assessment (administered within the app), participants will be randomised to receive one of two versions of the Headgear application: 1) Intervention (a 30-day mental health intervention focusing on behavioural activation and mindfulness), or 2) attention control app (mood monitoring for 30 days). Participants will be blinded to their allocation. Analyses will be conducted within an intention to treat framework using mixed modelling. DISCUSSION: The results of this trial will provide valuable information about the effectiveness of mhealth interventions in the treatment of depressive symptoms in a workplace context. TRIAL REGISTRATION: The current trial is registered with the Australian and New Zealand Clinical Trials Registry ( ACTRN12617000547347 , Registration date: 19/04/2017)

The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Purpose: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging. Methods: All patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21-76 years) undergoing PET or PET/CT for staging or restaging were analysed. Results: In 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging. Conclusion: Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical intervention

Defective Expression and Function of the Leukocyte Associated Ig-like Receptor 1 in B Lymphocytes from Systemic Lupus Erythematosus Patients

Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20+ B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior

Valuing Health Gain from Composite Response Endpoints for Multisystem Diseases

Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation