A mobile phone application for the assessment and management of youth mental health problems in primary care: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The <it>mobiletype </it>program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review.</p> <p>Methods</p> <p>We conducted a randomised controlled trial in primary care to examine the mental health benefits of the <it>mobiletype </it>program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale.</p> <p>Results</p> <p>Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the <it>mobiletype </it>program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes.</p> <p>Conclusions</p> <p>Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00794222">NCT00794222</a>.</p

Brief Exposure to Sensory Cues Elicits Stimulus-Nonspecific General Sensitization in an Insect

The effect of repeated exposure to sensory stimuli, with or without reward is well known to induce stimulus-specific modifications of behaviour, described as different forms of learning. In recent studies we showed that a brief single pre-exposure to the female-produced sex pheromone or even a predator sound can increase the behavioural and central nervous responses to this pheromone in males of the noctuid moth Spodoptera littoralis. To investigate if this increase in sensitivity might be restricted to the pheromone system or is a form of general sensitization, we studied here if a brief pre-exposure to stimuli of different modalities can reciprocally change behavioural and physiological responses to olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and subsequent behavioural tests were carried out to reveal possible intra- and cross-modal effects. Attraction to pheromone, monitored with a locomotion compensator, increased after exposure to olfactory and gustatory stimuli. Behavioural responses to sucrose, investigated using the proboscis extension reflex, increased equally after pre-exposure to olfactory and gustatory cues. Pheromone-specific neurons in the brain and antennal gustatory neurons did, however, not change their sensitivity after sucrose exposure. The observed intra- and reciprocal cross-modal effects of pre-exposure may represent a new form of stimulus-nonspecific general sensitization originating from modifications at higher sensory processing levels

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Emotional self-awareness and depressive symptoms: an investigation of an early intervention mobile phone self-monitoring program for adolescents

© 2012 Dr. Sylvia D. KauerPublication included in thesis:Kauer, S. D., Reid, S. C., Crooke, A. H. D., Khor, A., Hearps, S. J. C., Jorm, A. F., et al. (2012). Self-monitoring using mobile phones in the early stages of adolescent depression: randomised controlled trial with an attention comparison group to examine the mediating effect of emotional self-awareness. Journal of Medical Internet Research, 14(3). DOI: 10.2196/jmir.1858Up to 30% of adolescents experience depressive symptoms before 18 years of age and are at risk of developing severe recurrent depression. There is, however, a lack of appropriate treatments available for these young people. Self-monitoring is often used in therapy to increase awareness about mood and distress, and is likely to decrease depressive symptoms. Furthermore, self-monitoring has potential as an early intervention tool for young people at risk of depression, particularly when mobile phones are used as a medium. Using both qualitative and quantitative methods, this thesis investigates the concept of emotional self-awareness (ESA) and its mediating role in the relationship between self-monitoring and depressive symptoms. To this end, several studies were conducted. First, a systematic literature review examining the benefits of ESA was conducted. A review of 50 publications found five common themes throughout the literature regarding ESA: (a) becoming aware of an emotional experience; (b) the ability to define and distinguish specific feelings; (c) identifying the contextual factors surrounding emotions; (d) communication of emotional knowledge; and (e) analysing emotional events to make decisions. Second, a post-hoc qualitative study examined secondary school students’ general feedback about ESA after self-monitoring. Spontaneous feedback from 20% of participants reported at least one ESA theme after completion of the self-monitoring program. Third, following from the post-hoc study, in-depth qualitative interviews were conducted with 37 young people after self-monitoring, specifically targeting ESA. This study provided rich descriptive detail about the themes of ESA from young people’s perspectives. Fourth, a preliminary measure of ESA was developed and tested with 22 young people with subclinical depressive symptoms, recruited from two general practitioners in a rural setting. This small-scale mixed-methods study combined an in-depth qualitative interview and a quantitative measure of ESA. Young people with high scores on the ESA measure had a different qualitative experience than those with low scores. Last, a randomised controlled trial examined the effects of self-monitoring on depressive symptoms when mediated by ESA. Young people with mild or more depressive symptoms were recruited from primary care settings and randomised into an intervention group (n = 68) or an attention-comparison group (n = 46). Mediation analysis demonstrated that self-monitoring significantly increased ESA in the intervention group when compared with the comparison group and that an increase in ESA significantly decreased depressive symptoms. Furthermore, there was a medium size of indirect effect (κ2 = 0.44) for depressive symptoms per week indirectly through ESA when compared with the comparison group. In summary, a useful model of ESA was developed in this thesis and tested across the studies suggesting that self-monitoring can increase ESA, which in turn, decreases depressive symptoms. Mobile phones are well suited to early intervention programs, providing an alternative to watchful waiting. Mobile phone self-monitoring programs should be considered as a first-step low-cost early intervention for young people who are at-risk of mental health problems. Self-monitoring has the advantages of helping young people increase their ESA while gaining more information about their mental health symptoms, which can also direct them to suitable interventions

Does screening for and intervening with multiple health compromising behaviours and mental health disorders amongst young people attending primary care improve health outcomes? A systematic review

Adolescence and young adulthood are important developmental periods. Screening for health compromising behaviours and mental health disorders during routine primary care visits has the potential to assist clinicians to identify areas of concern and provide appropriate interventions. The objective of this systematic review is to investigate whether screening and subsequent interventions for multiple health compromising behaviours and mental health disorders in primary care settings improves the health outcomes of young people

A mobile phone application for the assessment and management of youth mental health problems in primary care: health service outcomes from a randomised controlled trial of mobiletype

BACKGROUND: GPs detect at best 50c of mental health problems in young people. Barriers to detecting mental health problems include lack of screening tools, limited appointment times and young people’s reluctance to report mental health symptoms to GPs. The mobiletype program is a mobile phone mental health assessment and management application which monitors mood, stress and everyday activities then transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. The current aims were to examine: (i) mobiletype as a clinical assistance tool, ii) doctor-patient rapport and, iii) pathways to care. METHODS: We conducted a randomised controlled trial in primary care with patients aged 14 to 24 years recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress and daily activities were monitored) or the attention-comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants and researchers were blind to group allocation at randomisation. GPs assessed the mobiletype program as a clinical assistant tool. Doctor-patient rapport was assessed using the General Practice Assessment Questionnaire Communication and Enablement subscales, and the Trust in Physician Scale (TPS). Pathways to care was measured using The Party Project’s Exit Interview. RESULTS: Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention n = 68, attention-comparison n = 46). T-tests showed that the intervention program increased understanding of patient mental health, assisted in decisions about medication/referral and helped in diagnosis when compared to the attention-comparison program. Mixed model analysis showed no differences in GP-patient rapport nor in pathways to care. CONCLUSIONS: We conducted the first RCT of a mobile phone application in the mental health assessment and management of youth mental health in primary care. This study suggests that mobiletype has much to offer GPs in the often difficult and time-consuming task of assessment and management of youth mental health problems in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT0079422

A Multi-Omic Precision Medicine Clinical Trial in Acute Leukemia

Background: Conventional precision medicine for cancer targets specific gene mutations, but single agent inhibitors rarely result in remission or improve survival in acute leukemia. Current functional screening strategies assay individual drugs, thus missing potential synergistic combinations. We therefore developed a multi-omic approach that integrates mutation data, gene expression data (transcriptome), and in vitro drug sensitivity (functional) data to select drugs including drug combinations for individual patients. Herein we report results of the clinical trial testing this concept [NCT02551718]. This study contributed to validation of 44 genes identified for which expression correlates with drug sensitivity (Lee S-I et al. Nat Commun 2018). Patients and Methods: Eligible patients failed at least 2 prior regimens, or if adverse risk, one multi-drug intensive regimen, had ECOG PS 0-3 and at least 1 million blasts in blood, marrow, tissue or fluid for analysis. The original enrollment was 25 patients to establish feasibility, and the study was later expanded to provide an option for refractory patients. Samples were obtained from the 54 consented patients (44 AML, 8 ALL, 2 acute leukemias of ambiguous lineage). Median age is 58 (range 23-82) and 31.5% of patients had an antecedent hematologic disorder. Of the AML patients (n=44), 7 were favorable, 13 intermediate, and 24 adverse risk (ELN 2017). Patients had a median of 3 prior treatments (range 1-6); 39 patients (72%) had relapsed after prior complete remission (CR) with median duration of 6 months (m) (range: 0-52 m), and 20 had relapsed after allogeneic transplant, 8 within the first 100 days, and 3 never achieved a CR after transplant. Enriched blasts were assayed in a custom CLIA-approved high throughput sensitivity (HTS) screen with 153 drugs and combinations, both conventional and targeted inhibitors, both FDA approved and investigational. Results were obtained within a mean of 5.2 (range 4-7) days. Mutation testing was performed by Invivoscribe using MyAML® targeted NGS panel. Clinical outcomes examined were peripheral blast reduction, response and survival. Results: Twenty-nine patients (53.7%; 25 AML, 2 ALL, 2 acute leukemias of ambiguous lineage) received therapy based on the HTS and mutation analysis. The remaining patients did not receive protocol treatment for a variety of reasons, including insufficient marrow blasts for testing, opting for palliative care, returning to their local area, denial by insurance , lack of access to investigational drugs, or medical complications making them ineligible. Of the 22 patients who had circulating peripheral blasts, 21 (95%) had a reduction, including 7 eradication, of circulating peripheral blasts following therapy. The median number of assay-directed regimens patients received was 2 (range 1-10, mean 2.5). Therapies administered are shown in the Table. Mutation testing on 47 patients revealed that 32 samples (68%) harbored mutations for which an approved or investigational targeted inhibitor could be considered (Figure 1). Figure 2 shows the heatmaps for individual patient mutations and drug sensitivity. Median survival following initiation of protocol therapy was 70 days (range 19-811). Of these often heavily pre-treated patients, 2 achieved CR, 1 CRi, and 6 had partial remissions (PRs), overall response rate (ORR) 31%. It was not always possible to obtain the top drugs if the use was off label or they were investigational, so drugs were selected that were lower in the ranked list of IC50s. When we observed 1-3 log reduction in IC50s for a combination compared to the single agents, the combination regimen would be recommended. For the 9 patients who received intensive combination regimens, there were 1 CR and 2 PRs, (ORR 33%), and for the 13 who received low intensity regimens, there was 1 CR, 1 CRi and 1 PR (ORR 23%). Enrolled allogeneic transplant recipients who received study treatment had a median survival of 476 days post-transplant compared to 340 days for those who did not receive assay guided therapy. Conclusions: This study demonstrates the feasibility of simultaneous collection of genomics, gene expression, and functional drug sensitivity data with the intent to guide choice of therapy. Responses were observed after study guided treatment. Future trials will incorporate new algorithms based on the correlative analyses obtained by this study to optimize treatment choices. Disclosures Becker: The France Foundation: Honoraria; Accordant Health Services/Caremark: Consultancy; AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding. Oehler:NCCN: Consultancy. Blau:All4Cure: Equity Ownership. Hammer:Glycomimetics: Consultancy. Cassaday:Kite/Gilead: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests. Scott:Agios: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Walter:Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; Seattle Genetics: Research Funding; Race Oncology: Consultancy; Pfizer: Consultancy, Research Funding; New Link Genetics: Consultancy; Boston Biomedical: Consultancy; Boehringer Ingelheim: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy. Gardner:Abbvie: Speakers Bureau. Carson:Invivoscribe, Inc: Employment. Patay:Invivoscribe, Inc: Employment. OffLabel Disclosure: Bortezomib is approved for multiple myeloma. Cladribine is approved for hairy cell leukemia. Etoposide is approved for small cell lung and testicular cancer. Sorafenib is approved for hepatocellular and renal cell carcinoma, thyroid cancer. Romidepsin is approved for T cell lymphoma. Decitabine is approved for myelodysplastic syndrome. Gemcitabine is approved for non small cell lung cancer and ovarian cancer. Vinblastine is approved for breast cancer, choriocarcinoma, Hodgkin lymphoma, Kaposi sarcoma, mycosis fungoides, NHL, and testicular cancer. Trametinib is approved for melanoma, anaplastic thyroid and non small cell lung cancer. Omacetaxine is approved for CML. </jats:sec