Universal mental health screening with a focus on suicidal behaviour using smartphones in a Mexican rural community: Protocol for the SMART-SCREEN population-based survey

Introduction Mental disorders represent the second cause of years lived with disability worldwide. Suicide mortality has been targeted as a key public health concern by the WHO. Smartphone technology provides a huge potential to develop massive and fast surveys. Given the vast cultural diversity of Mexico and its abrupt orography, smartphone-based resources are invaluable in order to adequately manage resources, services and preventive measures in the population. The objective of this study is to conduct a universal suicide risk screening in a rural area of Mexico, measuring also other mental health outcomes such as depression, anxiety and alcohol and substance use disorders. Methods and analysis A population-based cross-sectional study with a temporary sampling space of 9 months will be performed between September 2019 and June 2020. We expect to recruit a large percentage of the target population (at least 70%) in a short-term survey of Milpa Alta Delegation, which accounts for 137 927 inhabitants in a territorial extension of 288 km 2. They will be recruited via an institutional call and a massive public campaign to fill in an online questionnaire through mobile-assisted or computer-assisted web app. This questionnaire will include data on general health, validated questionnaires including Well-being Index 5, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale 2, Alcohol Use Disorders Identification Test, selected questions of the Drug Abuse Screening Test and Columbia-Suicide Severity Rating Scales and Diagnostic and statistical manual of mental disorders (DSM-5) questions about self-harm. We will take into account information regarding time to mobile app response and geo-spatial location, and aggregated data on social, demographical and environmental variables. Traditional regression modelling, multilevel mixed methods and data-driven machine learning approaches will be used to test hypotheses regarding suicide risk factors at the individual and the population level. Ethics and dissemination Ethical approval (002/2019) was granted by the Ethics Review Board of the Hospital Psiquiátrico Yucatán, Yucatán (Mexico). This protocol has been registered in ClinicalTrials.gov. The starting date of the study is 3 September 2019. Results will serve for the planning and healthcare of groups with greater mental health needs and will be disseminated via publications in peer-reviewed journal and presented at relevant mental health conferences. Trial registration number NCT04067063

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Activation of System xc- Trafficking via an Akt-dependent Signal Transduction Pathway

System xc- is a heterodimeric plasma membrane transporter involved in the exchange of intracellular glutamate for extracellular cystine. As such, this transporter plays a critical role in the production of the antioxidant glutathione. Previous studies in our lab have demonstrated that xCT cell surface expression increases within ten minutes of exposure to H2O2 in confluent U138MG human glioma cells. This study sought to begin to characterize the mechanism by which H2O2 regulates xCT trafficking. We hypothesized that Akt signaling is necessary for H2O2-mediated trafficking of of xCT. A significant increase in Akt phosphorylation was observed in U138MG cells following ten-minute exposure to 3 mM H2O2 compared to vehicle-treated cells using western blot analysis. Treatment with the Akt inhibitor 10-DEBC (2.5µM) for 30 minutes prior to and during H2O2 exposure resulted in a decrease in H2O2-induced phosphorylation of Akt at Ser473. Similar inhibition of Akt phosphorylation at Thr308 was observed following treatment of cells with 1.0µM API-2. Next, we used simultaneous treatment of cultured glioma cells with both inhibitors in the presence of H2O2 to determine if such treatment led to a reduction in the trafficking of endogenously expressed xCT to the plasma membrane. Preliminary data suggests that Akt activation is necessary for H2O2-induced trafficking xCT to the membrane in cultured glioma cells. To determine if the regulation of xCT cell surface expression is ubiquitous, not limited to human glioma cells where xCT is often overexpressed, we studied the role Akt plays in the trafficking of recombinantly expressed xCT in COS-7 cells. COS-7 cells transfected with myc-tagged xCT, 4F2HC and a constitutively active form of Akt showed higher levels of xCT localized to the membrane compared with cells transfected with a dominant negative Akt. These data suggest that Akt is an important regulator of xCT cell surface expression

WebWiseTclTk: A Safe-Tcl/Tk-based Toolkit Enhanced for the World Wide Web

. The WebWiseTclTk toolkit is an enhancement of the existing feature set of SafeTcl and Safe-Tk, without compromising security. The toolkit re-defines the functionality of the auto load mechanism in Tcl such that it works for packages located anywhere on the World Wide Web. It also re-introduces several commands not available in Safe-Tk such as toplevel and menu to provide a much richer feature set of Tk commands. The toolkit is written entirely in Safe-Tcl/Tk and uses the home policy for running applications as Tcl-plugins. The toolkit supports (1) creation of new Web-based Tcl applications with greatly enhanced functionality, and (2) migration of existing Tcl applications to the Web by merely writing an encapsulation script. We demonstrate the capabilities of the WebWiseTclTk toolkit by readily creating an encapsulation script for Web-based execution of the Tk Widget Demonstrations, distributed with the core Tcl/Tk. Note.This document has been published for viewing on the Web in Post..

Internet-based Workflows: A Paradigm For Dynamically Reconfigurable Desktop Environments

The Internet-based desktop environment as defined in this paper consists of a cross-platform browser, a number of server icons (host nodes), a number of application icons (program nodes) and a number of data icons (file nodes). In contrast to typical desktops of today, where data icons may be dragged and dropped onto application icons for execution, this environment allows (1) user-defined and reconfigurable execution sequences by creating dependency edges between program nodes (application icons) and file nodes (data icons); (2) data-dependent execution sequences by dynamic scheduling of path as well as loop executions; (3) host-transparency as to the location of applications and data (both can reside on any host with a unique IP address). We demonstrate that the Internet-based workflow paradigm is suitable for creation of dynamically reconfigurable desktop environments. In related research, we show that the proposed desktop is particularly suitable for making such an environment coll..

The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited. METHODS: A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI). RESULTS: We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy. DISCUSSION: Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes