Outcomes of telephone-delivered low-intensity cognitive behaviour therapy (LiCBT) to community dwelling Australians with a recent hospital admission due to depression or anxiety: MindStep™

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madeBackground In 2006, the British government launched ‘Improving Access to Psychological Therapies’ (IAPT), a low intensity cognitive behaviour therapy intervention (LiCBT) designed to manage people with symptoms of anxiety and depression in the community. The evidence of the effectiveness of IAPT has been demonstrated in multiple studies from the UK, USA, Australia and other countries. MindStep™ is the first adaptation of IAPT in Australia, delivered completely by telephone, targeting people with a recent history of a hospital admission for mental illnesses within the private health system. This paper reports on the outcome of the first 17 months of MindStep™ implemented across Australia from March 2016. Methods This prospective observational study investigated the MindStep™ program in a cohort of clients with a recent hospitalisation for mental illnesses. The study used quantitative methods to compare pre-post treatment clinical measures (N = 680) using Patient Health Questionnaire (PHQ-9) and the Generalised Anxiety Disorder (GAD-7). This study also included in-depth interviews with participants (N = 14) and coaches (N = 4) to determine the feasibility and acceptability of the program. Results Of the 867 clients referred to MindStep™, 757 had initial assessments by phone making an enrolment rate of 87.3%. Following assessment, 680 commenced treatment and of them, 427 (62.7%) completed treatment. According to ‘per-protocol’ analysis (N = 427), there was a large effect size for post-treatment PHQ-9 (d = 1.03) and GAD-7 (d = 0.99) scores; reliable recovery rate was 62% (95% CI: 57–68%). For intent-to-treat analysis using multiple imputation (N = 680), effect sizes were also large for pre-post treatment change: PHQ-9 (d = 0.78) and GAD-7 (d = 0.76). The reliable recovery rate was 49% (95% CI: 45–54%). Qualitative findings supported these claims where participants were positive about MindStep™ and found the telephone delivery and use of mental health coaches highly acceptable. Conclusions MindStep™ has demonstrated encouraging outcomes that suggest LiCBT can be successfully delivered to people with a history of hospital admissions for anxiety and depressive disorders and achieve target recovery rates of > 50%. Other promising evaluation findings indicate the MindStep™ option is acceptable, feasible and safe within the stepped models of mental health care delivery in Australia

The mTOR Signalling Pathway in Human Cancer

The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. It is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals, and essential signalling pathways, such as PI3K, MAPK and AMPK, in order to control cell growth, proliferation and survival. mTORC2 is considered resistant to rapamycin and is generally insensitive to nutrients and energy signals. It activates PKC-α and AKT and regulates the actin cytoskeleton. Deregulation of multiple elements of the mTOR pathway (PI3K amplification/mutation, PTEN loss of function, AKT overexpression, and S6K1, 4EBP1 and eIF4E overexpression) has been reported in many types of cancers, particularly in melanoma, where alterations in major components of the mTOR pathway were reported to have significant effects on tumour progression. Therefore, mTOR is an appealing therapeutic target and mTOR inhibitors, including the rapamycin analogues deforolimus, everolimus and temsirolimus, are submitted to clinical trials for treating multiple cancers, alone or in combination with inhibitors of other pathways. Importantly, temsirolimus and everolimus were recently approved by the FDA for the treatment of renal cell carcinoma, PNET and giant cell astrocytoma. Small molecules that inhibit mTOR kinase activity and dual PI3K-mTOR inhibitors are also being developed. In this review, we aim to survey relevant research, the molecular mechanisms of signalling, including upstream activation and downstream effectors, and the role of mTOR in cancer, mainly in melanoma

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Defining work-focused cognitive behavioural therapy (W-CBT) and whether it is effective at facilitating return to work for people experiencing mental health conditions: A systematic review and narrative synthesis

It is unclear what constitutes Work Focused Cognitive Behaviour Therapy (W-CBT). This review sought to define W-CBT and ascertain its effectiveness at facilitating return to work (RTW) for people experiencing mental health conditions. A systematic review and narrative synthesis were undertaken. Five databases were searched (Medline, ProQuest, PsychInfo, Scopus, and Web of Science). English publications with an intervention combining CBT with RTW were selected. Quality checklists from the Joanna Briggs Institute were applied. Searching yielded 16,863 results. 23 moderate-to-high quality studies from 25 articles were included (13 experimentally designed studies, 3 pilots/case studies and 7 reviews). Results indicated W-CBT is effective at facilitating RTW for mild-to-moderate mental health conditions. For a program to be labelled W-CBT it is recommended it is (1) a stand-alone intervention; (2) delivered with an understanding RTW is the goal; and, (3) the CBT components are always framed by matters, subjects and contexts related to work