Protocol for a randomised controlled trial evaluating the effectiveness of a CBT-based smartphone application for improving mental health outcomes in adolescents: the MobiliseMe study.

BACKGROUND: Depression is a leading cause of disability in adolescents, however few receive evidence-based treatment. Despite having the potential to overcome barriers to treatment uptake and adherence, there are very few CBT-based smartphone apps for adolescents. To address this gap, we developed ClearlyMe®, a self-guided CBT smartphone app for adolescent depression and anxiety. ClearlyMe® consists of 37 brief lessons containing core CBT elements, accessed either individually or as part of a 'collection'. Here, we describe the protocol for a randomised controlled trial aiming to evaluate the effect of ClearlyMe® on depressive symptoms and secondary outcomes, including engagement, anxiety and wellbeing, when delivered with and without guided support compared to an attention matched control. METHODS: We aim to recruit 489 adolescents aged 12-17 years with mild to moderately-severe depressive symptoms. Participants will be screened for inclusion, complete the baseline assessment and are then randomly allocated to receive ClearlyMe® (self-directed use), ClearlyMe® with guided SMS support (guided use) or digital psychoeducation (attention-matched control). Depressive symptoms and secondary outcomes will be assessed at 6-weeks (primary endpoint) and 4-months post-baseline (secondary endpoint). Engagement, conceptualised as uptake, adherence and completion, will also be assessed 6-weeks post-baseline. Mixed-effects linear modelling will be used to conduct intention-to-treat analyses to determine whether reductions in depressive symptoms and secondary outcomes are greater for conditions receiving ClearlyMe® relative to control at 6-weeks and 4-months post-baseline and greater for intervention adherers relative to non-adherers. To minimise risk, participants will be encouraged to use the Get Help section of the app and can also opt to receive a call from the team clinical psychologist at baseline, and at the 6-week and 4-month post-baseline assessments when reporting suicidal ideation. DISCUSSION: This is the first clinical trial examining a CBT smartphone app specifically designed for adolescent depression. It will provide empirical evidence on the effects of ClearlyMe® on depressive symptoms when used with and without guided support. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12622000131752). UNIVERSAL TRIAL NUMBER: U1111-1271-8519.

A mixed methods pilot and feasibility open trial of internet-delivered cognitive behaviour therapy (iCanADAPT Advanced) for people with advanced cancer with depression and/or anxiety.

PURPOSE: Evaluate the feasibility, acceptability and potential efficacy of a form of online therapy for clinical depression and/or anxiety in people living with advanced cancer. METHODS: A single-arm open trial of a six-lesson clinician-supervised, internet-delivered cognitive behavioural therapy (iCBT) transdiagnostic intervention (iCanADAPT Advanced) was undertaken. Qualitative (semi-structured telephone interview conducted at 3-months) and quantitative data (questionnaires collected at pre-, post-, and 3-month follow-up) were analysed. RESULTS: 27 participants partook (26 women, 56% breast cancer, mean age 56yo; average number of mental health diagnoses 1.8, with majority (81%) meeting criteria for generalised anxiety disorder). Feasibility - Unanticipated numbers (48%) of participants had physical health deterioration (cancer progression or death). iCBT had high adherence overall (completion rates: 37% did 6 lessons; 70% did 4 lessons) but adherence was higher for those whose cancer remained stable (completion rates: 43% did 6 lessons; 85% did 4 lessons). Acceptability - the intervention was acceptable to the majority of participants, with high treatment satisfaction. Advisory data was achieved regarding future versions. Potential efficacy - regardless of physical health status, participants who completed the iCBT showed a significant decrease over time in anxiety and depression symptoms. CONCLUSIONS: Online therapies may be useful in assisting those living with advanced cancer dealing with clinical depression and anxiety disorders. The specific modality of clinician supervised iCBT has significant potential to be a suitable modality of online therapy.

Modeling the Mechanisms by Which Coexisting Biomolecular RNA-Protein Condensates Form.

Liquid-liquid phase separation is an emerging mechanism for intracellular organization. This work presents a mathematical model to examine molecular mechanisms that yield phase-separated droplets composed of different RNA-protein complexes. Using a Cahn-Hilliard diffuse interface model with a Flory-Huggins free energy scheme, we explore how multiple (here two, for simplicity) protein-RNA complexes (species) can establish a heterogeneous droplet field where droplets with single or multiple species phase separate and evolve during coarsening. We show that the complex-complex de-mixing energy tunes whether the complexes co-exist or form distinct droplets, while the transient binding kinetics dictate both the timescale of droplet formation and whether distinct species phase separate into droplets simultaneously or sequentially. For specific energetics and kinetics, a field of droplets driven by the formation of only one protein-RNA complex will emerge. Slowly, the other droplet species will accumulate inside the preformed droplets of the other species, allowing them to occupy the same droplet space. Alternatively, unfavorable species mixing creates a parasitic relationship: the slow-to-form protein-RNA complex will accumulate at the surface of a competing droplet species, siphoning off the free protein as it is released. Once this competing protein-RNA complex has sufficiently accumulated on the droplet surface, it can form a new droplet that is capable of sharing an interface with the first complex droplet but is not capable of mixing. These results give insights into a wide range of phase-separation scenarios and heterogeneous droplets that coexist but do not mix within the nucleus and the cytoplasm of cells.

Randomised controlled trial of internet-delivered cognitive behaviour therapy for clinical depression and/or anxiety in cancer survivors (iCanADAPT Early).

PURPOSE: To evaluate internet-delivered cognitive behavioural therapy (iCBT) on clinical depression and/or anxiety, distress, fear of cancer recurrence, and quality of life in cancer survivors. METHODS: Random assignation of 114 participants to iCBT or treatment-as-usual (TAU). The clinician-supervised iCBT program (iCanADAPT Early) consisted of eight lessons over 16 weeks. Self-report questionnaires occurred at baseline, midpoint, and posttreatment for both groups with 3-month follow-up for iCBT participants. A mixed modelling approach to compare groups occurred. RESULTS: iCBT was superior to TAU on all outcome measures at posttreatment. Compared with TAU, the iCBT group showed a significant decrease over time in anxiety and depression symptoms (primary outcome, Hospital Anxiety and Depression Scale, Hedges g = 1.51). Additionally the iCBT group had significantly lower general distress (Kessler-10, g = 1.56), fear of cancer recurrence (Fear of Cancer Recurrence Inventory, g = 0.39), and significantly higher quality of life (Functional Assessment of Cancer Therapy-General, g = 0.74) at posttreatment compared with the TAU group. High adherence and satisfaction were found for iCBT with low clinician time. CONCLUSION: Clinician-supervised iCBT has significant benefits for cancer survivors with clinical depression and anxiety disorders.

Computer therapy for the anxiety and depression disorders is effective, acceptable and practical health care: An updated meta-analysis.

BACKGROUND: A 2010 meta-analysis of internet-delivered CBT (iCBT) RCTs argued 'computer therapy for the anxiety and depressive disorders was effective, acceptable and practical health care' without data on effectiveness or practicality in routine practice. METHODS: Databases, reviews and meta-analyses were searched for randomised controlled trials of cCBT or iCBT versus a control group (care as usual, waitlist, information control, psychological placebo, pill placebo, etc.) in people who met diagnostic criteria for major depression, panic disorder, social anxiety disorder or generalised anxiety disorder. Number randomised, superiority of treatment versus control (Hedges'g) on primary outcome measure, length of follow-up, follow up outcome, patient adherence and satisfaction/harm were extracted; risk of bias was assessed. A search for studies on effectiveness of iCBT in clinical practice was conducted. RESULTS: 64 trials were identified. The mean effect size (efficacy) was g = 0.80 (NNT 2.34), and benefit was evident across all four disorders. Improvement was maintained at follow-with good acceptability. Research probity was good, and bias risk low. In addition, nine studies comparing iCBT with traditional face-to-face CBT and three comparing iCBT with bibliotherapy were identified. All three modes of treatment delivery appeared equally beneficial. The results of effectiveness studies were congruent with the results of the efficacy trials. LIMITATIONS: Studies variably measured changes in quality of life and disability, and the lack of comparisons with medications weakens the field. CONCLUSIONS: The conclusions drawn in the original meta-analysis are now supported: iCBT for the anxiety and depressive disorders is effective, acceptable and practical health care.

iCanADAPT Early protocol: randomised controlled trial (RCT) of clinician supervised transdiagnostic internet-delivered cognitive behaviour therapy (iCBT) for depression and/or anxiety in early stage cancer survivors -vs- treatment as usual.

BACKGROUND: This RCT with two parallel arms will evaluate the efficacy of an internet-delivered transdiagnostic cognitive behavioural therapy (iCBT) intervention for the treatment of clinical depression and/or anxiety in early stage cancer survivors. METHODS/DESIGN: Early stage cancer survivors will be recruited via the research arm of a not-for-profit clinical research unit and randomised to an intervention (iCBT) group or a 'treatment as usual' (TAU) control group. The minimum sample size for each group is 45 people (assuming effect size > 0.6, power of 80%, and alpha at .05), but 10% more will be recruited to account for attrition. A solitary or cumulative diagnosis(es) of Major Depressive Episode (current), Generalised Anxiety Disorder, Illness Anxiety Disorder, Panic Disorder, Agoraphobia, and/or Adjustment disorder will be determined using modules from the Anxiety Disorders Interview Schedule for DSM-5. Depression and anxiety levels with be measured via the total score of the Hospital Anxiety and Depression scale (HADS-T), the primary outcome measure. Secondary measures will include the Kessler 10 to measure general distress, the Fear of Cancer Recurrence Inventory (FCRI) to measure the specific fear of cancer recurrence and the Functional Assessment of Cancer Therapy, General Version 4 (FACT-G) for self-report of physical, social, emotional and functional well-being. iCBT participants will complete the measures before lessons 1 and 5, at post-treatment and at 3-month follow-up. The TAU group will complete similar measures at weeks 1, 8 and 16 of the waiting period. Program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at 3-month follow-up. Mediation analyses using PROCESS will be used to examine the association between change in depressive and anxious symptoms over time and changes in FCRI and FACT-G QOL in separate analysis. DISCUSSION: This is the first RCT looking at iCBT specifically for clinical depression and/or anxiety in a cancer population. Findings will help to direct the role of iCBT in streamlined psycho-social care pathways. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616000231448, registered 19th February 2016 ( www.anzctr.org.au ). This trial protocol is in compliance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.

Acceptability of an internet cognitive behavioural therapy program for people with early-stage cancer and cancer survivors with depression and/or anxiety: thematic findings from focus groups.

PURPOSE: We developed an eight-lesson internet-delivered CBT (iCBT) program targeting anxiety and depression in early-stage cancer and cancer survivors. To explore the acceptability of the program, we showed volunteers the first two lessons and asked for their views. METHODS: Focus groups (n = 3) and individual interviews (n = 5) were undertaken with 15 participants (11 survivors) with mainly breast (11 of the 15) cancer, who had reviewed intervention materials. Participants were asked to consider the acceptability of the iCBT program content and implementation design (timing, duration). Semi-structured questions guided discussion. Thematic analysis was conducted of participant reactions to the acceptability and/or suitability of materials created for use in a psychological intervention. We took a data-driven (inductive) approach to semantic theme development across the data set. RESULTS: Participants reported high acceptability of the internet delivery format, good engagement and user-friendly material. Participants were broadly supportive of combining depression and anxiety iCBT resources for early-stage cancer patients and survivors. Participants further indicated that a separate course would be needed to address the needs of patients with advanced stage disease. CONCLUSIONS: Participants welcomed the general development of an internet-delivered CBT intervention program to treat patients with clinical depression and/or anxiety. Furthermore, the sessions reviewed were highly acceptable to all participants. Study findings informed researchers on the development of iCBT resources for the cancer community.

Internet cognitive behavioural therapy for mixed anxiety and depression: a randomized controlled trial and evidence of effectiveness in primary care.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) have the highest co-morbidity rates within the internalizing disorders cluster, yet no Internet-based cognitive behavioural therapy (iCBT) programme exists for their combined treatment. METHOD: We designed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression. Study 1 was a randomized controlled trial (RCT) comparing the iCBT programme (n = 46) versus wait-list control (WLC; n = 53) for patients diagnosed by structured clinical interview with MDD, GAD or co-morbid GAD/MDD. Primary outcome measures were the Patient Health Questionnaire nine-item scale (depression), Generalized Anxiety Disorder seven-item scale (generalized anxiety), Kessler 10-item Psychological Distress scale (distress) and 12-item World Health Organization Disability Assessment Schedule II (disability). The iCBT group was followed up at 3 months post-treatment. In study 2, we investigated the adherence to, and efficacy of the same programme in a primary care setting, where patients (n = 136) completed the programme under the supervision of primary care clinicians. RESULTS: The RCT showed that the iCBT programme was more effective than WLC, with large within- and between-groups effect sizes found (>0.8). Adherence was also high (89%), and gains were maintained at 3-month follow-up. In study 2 in primary care, adherence to the iCBT programme was low (41%), yet effect sizes were large (>0.8). Of the non-completers, 30% experienced benefit. CONCLUSIONS: Together, the results show that iCBT is effective and adherence is high in research settings, but there is a problem of adherence when translated into the 'real world'. Future efforts need to be placed on developing improved adherence to iCBT in primary care settings.

Study supports hiring more part-time RNs.

Although not a panacea for the national shortage of nurses, the addition of more part-time nurses may allow hospitals greater flexibility in scheduling full-time personnel.