BackUp : development and evaluation of a smart-phone application for coping with suicidal crises

Background : Suicide is a major public health issue and has large impact on the lives of many people. Innovative technologies such as smartphones could create new possibilities for suicide prevention, such as helping to overcome the barriers and stigma on help seeking in case of suicidal ideation. Due to their omnipresence, smartphone apps can offer suicide prevention tools very fast, they are easily-accessible, low-threshold and can help overcome some of the help-seeking barriers suicidal people experience. This article describes the development, testing and implementation of a mobile application for coping with suicidal crisis: BackUp. Methods : Based on the analysis of literature and existing suicide prevention apps several tools were identified as relevant to include in a suicide prevention app. The selected tools (a safety planning tool, a hope box, a coping cards module, and a module to reach out) are evidence based in a face to face context, and could be easily transferred into a mobile app. The testing of existing apps and the literature also revealed important guidelines for the technical development of the application. Results : BackUp was developed and tested by an expert panel (n = 9) and a panel of end users (n = 21). Both groups rated BackUp as valuable for suicide prevention. Suicidal ideation of the end user group was measured using the Beck Scale for Suicidal Ideation before and after testing BackUp, and showed a small but non-significant decrease. The majority of the testers used BackUp several times. All tools were evaluated as rather or very useable in times of suicidal crisis. Conclusion : BackUp was positively evaluated and indicates that self-help tools can have a positive impact on suicidal ideation. Apps in particular create opportunities in approaching people that are not reached by traditional interventions; on the other hand they can contribute to suicide prevention in addition to regular care. However, more research is needed on the impact and effect of suicide prevention apps

The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

<p>Abstract</p> <p>Background</p> <p>Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) are the three components of the once-daily, single tablet regimen (Atripla) for treatment of HIV-1 infection. Previous cell culture studies have demonstrated that the double combination of tenofovir (TFV), the parent drug of TDF, and FTC were additive to synergistic in their anti-HIV activity, which correlated with increased levels of intracellular phosphorylation of both compounds.</p> <p>Results</p> <p>In this study, we demonstrated the combinations of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV synergistically inhibit HIV replication in cell culture and synergistically inhibit HIV-1 reverse transcriptase (RT) catalyzed DNA synthesis in biochemical assays. Several different methods were applied to define synergy including median-effect analysis, MacSynergy^®II and quantitative isobologram analysis. We demonstrated that the enhanced formation of dead-end complexes (DEC) by HIV-1 RT and TFV-terminated DNA in the presence of FTC-triphosphate (TP) could contribute to the synergy observed for the combination of TFV+FTC, possibly through reduced terminal NRTI excision. Furthermore, we showed that EFV facilitated efficient formation of stable, DEC-like complexes by TFV- or FTC-monophosphate (MP)-terminated DNA and this can contribute to the synergistic inhibition of HIV-1 RT by TFV-diphosphate (DP)+EFV and FTC-TP+EFV combinations.</p> <p>Conclusion</p> <p>This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.</p

Efficacy and safety of fluticasone/formoterol combination therapy in patients with moderate-to-severe asthma

Background: The inhaled corticosteroid, fluticasone propionate, and the long-acting b2-adrenergic agonist, formoterol fumarate, are both highly effective treatments for bronchial asthma. This study (NCT00393952/EudraCT number: 2006-005989-39) compared the efficacy and safety of fluticasone/formoterol combination therapy (flutiform®; 250/10 mg) administered twice daily (b.i.d.) via a single aerosol inhaler, with the individual components (fluticasone 250 mg b.i.d.; formoterol 10 mg b.i.d.), in adult and adolescent patients with moderate-to-severe asthma. Methods: This was a 12-week, double-blind, randomised, parallel-group, multicentre, placebocontrolled phase 3 study. The co-primary efficacy endpoints were: i) the mean change in the forced expiratory volume in the first second (FEV1) from morning pre-dose at baseline to pre-dose at week 12 (fluticasone/formoterol 250/10 mg vs. formoterol), ii) the mean change in FEV1 from morning pre-dose at baseline to 2 h post-dose at week 12 (fluticasone/formoterol 250/10 mg vs. fluticasone), and iii) the number of patients who discontinued prematurely due to lack of treatment efficacy (fluticasone/formoterol 250/10 mg vs. placebo). The secondary endpoints included measures of lung function, disease control, and asthma symptoms. Safety was assessed based on adverse events, vital signs, and clinical laboratory evaluations. Results: Overall, 395 (70.9%) patients completed the study. Fluticasone/formoterol 250/10 mg b.i.d. was superior to the individual components and placebo for all three co-primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses. Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks. Conclusion: Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma

Online suicide risk detection using automatic text classification

Identifying individuals at risk for suicide is a key prevention objective. With the growing importance of online networks, signals of suicidal ideation and intent are increasingly expressed on the web. Particular advantages of online communication are that it can offer anonymity and a sense of control. There is evidence that introverted individuals are strongly motivated to communicate online, which leads to more self-disclosure. Although suicidal expressions may be recognized and responded to by peers, this does not always happen in an appropriate or timely fashion. It is therefore preferable to also have prevention specialists monitor user-generated content, if this is not in conflict with users' preferences, safety and privacy concerns. The huge volume of online content prohibits manual monitoring, so automatic filtering approaches are required to prevent information overload. Previous research has focused on solutions based on keyword searches. Their efficacy is limited, since search queries can only cover a limited range of explicit suicidal expressions, they typically return many irrelevant hits, and are not robust to spelling errors. This paper presents a suicide prevention approach based on automatic text classification. In supervised text classification, a system assigns each text to one of a number of predefined categories. In our use case, a text is an online post, and there are three categories: alarming posts that should be reviewed, suicide-related posts that are harmless, and irrelevant posts (i.e. the majority class). A set of 300,000 forum and blog messages was collected and partly labeled by staff and volunteers at the Belgian Suicide Prevention Centre (CPZ). We used natural language processing to represent each text as a rich set of features that should allow suicidality prediction, including words, characters, significant terms derived from transcripts from the CPZ emergency chat hotline, topic models capturing semantically related words, and the emotional orientation of words (positive, negative or neutral) based on two external sentiment lexicons. Support Vector Machines (SVM), a supervised machine learning technique, was trained, evaluated and optimized on the corpus to allow classification of unseen material. In practice, the model will classify newly posted content based on the knowledge it induced from the annotated training corpus, and notify a prevention specialist in case of a possibly alarming post. The experimental results show that both suicide-related and alarming messages can be detected with high precision (80 to 90%). As a result, the amount of noise generated by the system is minimal: only 1 or 2 out of ten messages flagged by the system is irrelevant. In terms of recall, a measure for how many relevant messages were missed, suicide-related content is almost always detected (90%, i.e. missing one in ten). Recall for alarming posts is lower, at around 60%, a problem mainly attributable to implicit references to suicide, which often go undetected. The text classification approach outperforms a system based on keyword searching, most notably in terms of precision. In order to evaluate performance in a real-world prevention setting, we also tested the system on datasets of increasing size in which the class skew was augmented and thus the incidence of suicide-related material was decreased. Interestingly, we observe that the system also scores well on large datasets with high class skew, making it usable in big data automated prevention. The results are a first and promising indication that text classification is a viable approach to online message filtering for suicide prevention purposes. Additional positive training data (i.e. messages that can be considered suicide-related) should allow further performance improvements. The resulting system is currently being validated on the message boards of two Belgian LGBT organizations. Volunteer website moderators, overwhelmed with the above-average amount of suicide-related content, receive training from CPZ professionals on how to screen possibly alarming content and how best to respond. The results of this study will be presented at IASR

Cost-effectiveness of a helpline for suicide prevention

We evaluated the cost-effectiveness and budget impact of a suicide helpline in Belgium, consisting of a telephone-and a chat service. An age-and gender-dependent Markov model with a ten-year time horizon and a one-year cycle length was developed, assuming a societal perspective, to predict cumulative costs and quality-adjusted life-years (QALYs) in the helpline users. The model included six transition states: the initial state (at risk), first attempt, re-attempt, follow-up, suicide and death from other causes. Data on the effect of the helpline and costs associated with model states were obtained from the literature. One-way and probabilistic sensitivity analyses were performed to capture uncertainty. In addition, the budget impact of the helpline was analysed. Over ten years, the telephone-as well as the chat service could avoid about 36% of suicides and attempts in this high-risk population. In males, 0.063 QALYs (95% confidence interval, CI 0.030-0.097) and 0.035 QALYs (95% CI -0.026-0.096) were gained by users of the telephone-and chat service respectively. The corresponding values for females were 0.019 QALYs (95% CI -0.015-0.052) and a QALY-neutral result of -0.005 (95% CI -0.071-0.062). There were net societal savings of respectively (sic)2382 (95% CI 1953-2859) and (sic)2282 (95% CI 1855-2758) in male users; (sic)2171 (95% CI 1735-2664) and (sic)2458 (95% CI 1945-3025) in female users. At the population level, an investment of (sic)218,899 saved (sic)1,452,022 for the public health service (national health insurance), mainly due to the telephone service. The analysis predicted that both means of telemedicine for suicide prevention in Flanders are cost-saving, and have a modest effect on QALYs

Usage of BackUp during testing period.

<p>Usage of BackUp during testing period.</p