Efficacy of BrighterSide, a Self-Guided App for Suicidal Ideation: Randomized Controlled Trial.

Background: Self-guided digital interventions can reduce the severity of suicidal ideation, although there remain relatively few rigorously evaluated smartphone apps targeting suicidality. Objective: This trial evaluated whether the BrighterSide smartphone app intervention was superior to a waitlist control group at reducing the severity of suicidal ideation. Methods: A total of 550 adults aged 18 to 65 years with recent suicidal ideation were recruited from the Australian community. In this randomized controlled trial, participants were randomly assigned to receive either the BrighterSide app or to a waitlist control group that received treatment as usual. The app was self-guided, and participants could use the app at their own pace for the duration of the study period. Self-report measures were collected at baseline, 6 weeks, and 12 weeks. The primary outcome was severity and frequency of suicidal ideation, and secondary outcomes included psychological distress and functioning and recovery. Additional data were collected on app engagement and participant feedback. Results: Suicidal ideation reduced over time for all participants, but there was no significant interaction between group and time. Similar improvements were observed for self-harm, functioning and recovery, days out of role, and coping. Psychological distress was significantly lower in the intervention group at the 6-week follow-up, but this was not maintained at 12 weeks. Conclusions: The BrighterSide app did not lead to a significant improvement in suicidal ideation relative to a waitlist control group. Possible reasons for this null finding are discussed.

Preliminary Evaluation of Lived Experience of Suicide Training: Short-, Medium- and Longer-Term Impacts of Our Voices in Action Training.

Despite increased participation and multiple workforce roles of those with lived experience in suicide prevention, there are no evaluated training programs to support this population. This study evaluated a training program aimed to prepare people for these important roles. Survey data at pre-, post- and at three- and 12-month follow-up were used measuring knowledge, attitudes, and self-efficacy, as well as psychological distress as a safety measure. Participants experienced significant gains in knowledge after training, although not all aspects of knowledge were maintained at follow-up. Self-efficacy was examined through confidence and empowerment. Confidence gains were significant at immediate and longer-term follow-up but gains in empowerment were not maintained over time. Participants' positive attitudes improved but this was not significant. There was no indication of increases in psychological distress in participants throughout the training and follow-up periods. Implications of these outcomes are discussed.

Optimising inhaler technique in chronic obstructive pulmonary disease: a complex issue.

Inhaled therapies play a central role in the management of chronic obstructive pulmonary disease (COPD); however, studies indicate that many patients do not use their inhaled medication as directed, resulting in decreased medication delivery and suboptimal disease control. Key factors that should be considered when evaluating whether patients are achieving optimal outcomes with inhaled therapies are: if patients are using a correct inhalation technique; if patients have adequate dexterity to use the prescribed inhaler; if patients have sufficient inspiratory flow rate to achieve adequate lung deposition (for dry powder inhalers); and if the inhaler is accepted by the patient. There are many different types of dry powder inhalers available for COPD medications and their specific features can affect ease of use and suitability and acceptability for individual patients and patients' preferences.

Self-reporting hybridisation assay for miRNA analysis.

Hybridisation assays, which are commonly used to analyse oligonucleotides such as siRNAs and miRNAs, often employ detection probes with fluorescent tags. The signal emitted by a fluorescent tag covers a broad range of wavelengths and this limits the multiplexing potential due to overlapping signals. A novel method of indirect oligonucleotide analysis has been developed which combines a hybridisation assay with cleavable small molecule mass tags using HPLC-ESI MS detection. A self-reporting detection probe has been designed which incorporates a DNA/RNA chimeric oligonucleotide sequence in the reporter region, which generates small nucleotide products upon RNase cleavage of the ribose-phosphate backbone. These small nucleotides can then serve as mass tags for the indirect detection of oligonucleotide analytes. The narrow mass range covered by a small molecule mass tag combined with the wide range of possible mass tags provides a high degree of multiplexing potential. This approach has been demonstrated for the analysis of a synthetic miRNA.

Self reporting RNA probes as an alternative to cleavable small molecule mass tags.

The large size of biological molecules such as proteins and oligonucleotides makes them inherently problematic to analyse and quantify directly by mass spectrometry. For these molecules, electrospray ionisation produces multiply charged species and associated alkali metal adducts which can reduce sensitivity and complicate quantification. Whereas time-of-flight mass analysers, often coupled to matrix-assisted laser desorption/ionisation, can have insufficient mass resolution to resolve these large molecules in the higher m/z range. This has led to the development of cleavable small molecule mass tag approaches for the indirect analysis of biomolecules such as proteins and oligonucleotides. Existing methodologies require the design and synthesis of a cleavable linker to join the biomolecule and the mass tag. Here, an alternative approach to small molecule mass tags is presented, which exploits the properties of the RNA molecule to afford self-reporting probes which can be easily synthesised using automated phosphoramidite chemistry. The sugar-phosphate backbone of RNA was used as a built-in enzyme cleavable linker and through the use of RNase digestion of bromine labelled oligonucleotides the observation of a range of small molecule mass tags by mass spectrometry is demonstrated. This study provides a proof-of-concept that RNase digestion can be used to produce labelled small molecule mass tags from oligonucleotide probes, thus eliminating the need for custom design and synthesis of a cleavable linker.

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Prediction of tandem mass spectrometric (MS/MS) fragmentation for non-peptidic molecules based on structure is of immense interest to the mass spectrometrist. If a reliable approach to MS/MS prediction could be achieved its impact within the pharmaceutical industry could be immense. Many publications have stressed that the fragmentation of a molecular ion or protonated molecule is a complex process that depends on many parameters, making prediction difficult. Commercial prediction software relies on a collection of general heuristic rules of fragmentation, which involve cleaving every bond in the structure to produce a list of 'expected' masses which can be compared with the experimental data. These approaches do not take into account the thermodynamic or molecular orbital effects that impact on the molecule at the point of protonation which could influence the potential sites of bond cleavage based on the structural motif. A series of compounds have been studied by examining the experimentally derived high-resolution MS/MS data and comparing it with the in silico modelling of the neutral and protonated structures. The effect that protonation at specific sites can have on the bond lengths has also been determined. We have calculated the thermodynamically most stable protonated species and have observed how that information can help predict the cleavage site for that ion. The data have shown that this use of in silico techniques could be a possible way to predict MS/MS spectra.