Digital Interventions for Stress Among Frontline Health Care Workers: Results From a Pilot Feasibility Cohort Trial.

BACKGROUND: The COVID-19 pandemic has challenged the mental health of health care workers, increasing the rates of stress, moral distress (MD), and moral injury (MI). Virtual reality (VR) is a useful tool for studying MD and MI because it can effectively elicit psychophysiological responses, is customizable, and permits the controlled study of participants in real time. OBJECTIVE: This study aims to investigate the feasibility of using an intervention comprising a VR scenario and an educational video to examine MD among health care workers during the COVID-19 pandemic and to use our mobile app for longitudinal monitoring of stress, MD, and MI after the intervention. METHODS: We recruited 15 participants for a compound intervention consisting of a VR scenario followed by an educational video and a repetition of the VR scenario. The scenario portrayed a morally challenging situation related to a shortage of life-saving equipment. Physiological signals and scores of the Moral Injury Outcome Scale (MIOS) and Perceived Stress Scale (PSS) were collected. Participants underwent a debriefing session to provide their impressions of the intervention, and content analysis was performed on the sessions. Participants were also instructed to use a mobile app for 8 weeks after the intervention to monitor stress, MD, and mental health symptoms. We conducted Wilcoxon signed rank tests on the PSS and MIOS scores to investigate whether the VR scenario could induce stress and MD. We also evaluated user experience and the sense of presence after the intervention through semi-open-ended feedback and the Igroup Presence Questionnaire, respectively. Qualitative feedback was summarized and categorized to offer an experiential perspective. RESULTS: All participants completed the intervention. Mean pre- and postintervention scores were respectively 10.4 (SD 9.9) and 13.5 (SD 9.1) for the MIOS and 17.3 (SD 7.5) and 19.1 (SD 8.1) for the PSS. Statistical analyses revealed no significant pre- to postintervention difference in the MIOS and PSS scores (P=.11 and P=.22, respectively), suggesting that the experiment did not acutely induce significant levels of stress or MD. However, content analysis revealed feelings of guilt, shame, and betrayal, which relate to the experience of MD. On the basis of the Igroup Presence Questionnaire results, the VR scenario achieved an above-average degree of overall presence, spatial presence, and involvement, and slightly below-average realism. Of the 15 participants, 8 (53%) did not answer symptom surveys on the mobile app. CONCLUSIONS: Our study demonstrated VR to be a feasible method to simulate morally challenging situations and elicit genuine responses associated with MD with high acceptability and tolerability. Future research could better define the efficacy of VR in examining stress, MD, and MI both acutely and in the longer term. An improved participant strategy for mobile data capture is needed for future studies. TRIAL REGISTRATION: ClinicalTrails.gov NCT05001542; https://clinicaltrials.gov/study/NCT05001542. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32240.

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study.

OBJECTIVES: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6, and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample. METHODS: A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n = 91), while responders continued ESC (i.e., ESC-Only, n = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models. RESULTS: In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F(2,54) = 8.00, p < 0.001, q = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF (r = -0.42, p = 0.004, q = 0.034) and SS (r = -0.43, p = 0.003, q = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction (r = -0.39, p = 0.009, q = 0.052). CONCLUSIONS: CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

Development of a data-driven digital phenotype profile of distress experience of healthcare workers during COVID-19 pandemic.

BACKGROUND AND OBJECTIVE: Due to the constraints of the COVID-19 pandemic, healthcare workers have reported acting in ways that are contrary to their moral values, and this may result in moral distress. This paper proposes the novel digital phenotype profile (DPP) tool, developed specifically to evaluate stress experiences within participants. The DPP tool was evaluated using the COVID-19 VR Healthcare Simulation of Stress Experience (HSSE) dataset (NCT05001542), which is composed of passive physiological signals and active mental health questionnaires. The DPP tool focuses on correlating electrocardiogram, respiration, photoplethysmography, and galvanic skin response with moral injury outcome scale (Brief MIOS). METHODS: Data-driven techniques are encompassed to develop a tool for robust evaluation of distress among participants. To accomplish this, we applied pre-processing techniques which involved normalization, data sanitation, segmentation, and windowing. During feature analysis, we extracted domain-specific features, followed by feature selection techniques to rank the importance of the feature set. Prior to classification, we employed k-means clustering to group the Brief MIOS scores to low, moderate, and high moral distress as the Brief MIOS lacks established severity cut-off scores. Support vector machine and decision tree models were used to create machine learning models to predict moral distress severities. RESULTS: Weighted support vector machine with leave-one-subject-out-cross-validation evaluated the separation of the Brief MIOS scores and achieved an average accuracy, precision, sensitivity, and F1 of 98.67%, 98.83%, 99.44%, and 99.13%, respectively. Various machine learning ablation tests were performed to support our results and further enhance the understanding of the predictive model. CONCLUSION: Our findings demonstrate the feasibility to develop a DPP tool to predict distress experiences using a combination of mental health questionnaires and passive signals. The DPP tool is the first of its kind developed from the analysis of the HSSE dataset. Additional validation is needed for the DPP tool through replication in larger sample sizes.

Development of Content for a Virtual Reality Simulation to Understand and Mitigate Moral Distress in Healthcare Workers.

Background In high-stakes situations, healthcare workers are prone to suffer moral injury, the psychological, social, and spiritual impact of events involving betrayal or transgression of one's own deeply held moral beliefs and values. As a result, this may negatively impact their capacity to provide adequate levels of care to patients. There is a lack of educational resources catered to help healthcare workers navigate ethical situations in clinical settings that may lead to or worsen moral distress. The aim of this report is to describe the methodology of development and resulting outcomes in the form of an educational resource that includes a virtual reality (VR) simulation to help healthcare workers understand and mitigate moral distress as a result of internal and external constraints at their workplaces. Methodology A study using a method outlining a set of constraint parameters, followed by ideation utilizing design thinking (DT), and concluding with a consensus-building exercise using Delphi methodology (DM) with a group of 13 experts in healthcare simulation, VR, psychiatry, psychology, and nursing. The constraints parameters included technology use (VR), use of experiential learning theory, and duration of the intervention (15 minutes). A DT process was performed to generate and expand on ideas on the scenario and intervention of a possible VR simulation which were funneled into a three-round DM to define the foundations of the VR simulation. Average, standard deviations, and free-text comments in the DM were used to assess the inclusion of the produced requirements. Finally, a focus group interview was conducted with the same experts to draft the VR simulation. Results Within the specified constraints, the DT process produced 33 ideas for the VR simulation scenario and intervention that served as a starting point to short-list the requirements in Round 1. In Rounds 1 to 2, 25 items were removed, needed revising, and/or were retained for the subsequent rounds, which resulted in eight items at the end of Round 2. Round 2 also required specialists to provide descriptions of potential scenarios and interventions, in which five were submitted. In Round 3, experts rated the descriptions as somewhat candidate to use in the final VR simulation, and the open feedback in this round proposed combining the elements from each of the descriptions. Using this data, a prototype of the VR simulation was developed by the project team together with VR designers. Conclusions This development demonstrated the feasibility of using the constraints-ideation-consensus approach to define the content of a possible VR simulation to serve as an educational resource for healthcare workers on how to understand and mitigate moral distress in the workplace. The methodology described in this development may be applied to the design of simulation training for other skills, thereby advancing healthcare training and the quality of care delivered to the greater society.

Males and females differ in reported sexual functioning with escitalopram treatment for major depressive disorder: A CAN-BIND-1 study report.

BACKGROUND: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. AIMS: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF. METHODS: In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10-20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery-Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week 8 as well as associations between pretreatment and eventual SF. RESULTS: For both sexes, overall sexual satisfaction improved among responders but not among nonresponders (p < 0.05). For females, overall SF frequency did not change significantly over time regardless of response status. For males, overall SF decreased significantly among nonresponders; orgasm decreased significantly among nonresponders and, to a lesser extent, among responders (p < 0.05). For both sexes, pretreatment SF was significantly associated with SF at Week 8 across all domains (p < 0.05). CONCLUSION: For both sexes, sexual satisfaction improves with response to escitalopram. For females, the response does not correspond to improvements in SF frequency. For males, SF frequency, particularly that of orgasm, declines regardless of response/nonresponse.ClinicalTrials.gov identifier: NCT01655706.

Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy.

OBJECTIVE: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects. METHODS: 188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects. RESULTS: For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05). CONCLUSION: Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.