What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial.

PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.

Comparison of the Working Alliance in Blended Cognitive Behavioral Therapy and Treatment as Usual for Depression in Europe: Secondary Data Analysis of the E-COMPARED Randomized Controlled Trial.

BACKGROUND: Increasing interest has centered on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioral therapy (bCBT) intervention for depression. OBJECTIVE: This study aimed to test the difference in working alliance scores between bCBT and treatment as usual (TAU), examine the association between working alliance and depression severity scores in both arms, and test for an interaction between system usability and working alliance with regard to the association between working alliance and depression scores in bCBT at 3-month assessments. METHODS: We conducted a secondary data analysis of the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment versus Treatment-as-usual) trial, which compared bCBT with TAU across 9 European countries. Data were collected in primary care and specialized services between April 2015 and December 2017. Eligible participants aged 18 years or older and diagnosed with major depressive disorder were randomized to either bCBT (n=476) or TAU (n=467). bCBT consisted of 6-20 sessions of bCBT (involving face-to-face sessions with a therapist and an internet-based program). TAU consisted of usual care for depression. The main outcomes were scores of the working alliance (Working Alliance Inventory-Short Revised-Client [WAI-SR-C]) and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) at 3 months after randomization. Other variables included system usability scores (System Usability Scale-Client [SUS-C]) at 3 months and baseline demographic information. Data from baseline and 3-month assessments were analyzed using linear regression models that adjusted for a set of baseline variables. RESULTS: Of the 945 included participants, 644 (68.2%) were female, and the mean age was 38.96 years (IQR 38). bCBT was associated with higher composite WAI-SR-C scores compared to TAU (B=5.67, 95% CI 4.48-6.86). There was an inverse association between WAI-SR-C and PHQ-9 in bCBT (B=-0.12, 95% CI -0.17 to -0.06) and TAU (B=-0.06, 95% CI -0.11 to -0.02), in which as WAI-SR-C scores increased, PHQ-9 scores decreased. Finally, there was a significant interaction between SUS-C and WAI-SR-C with regard to an inverse association between higher WAI-SR-C scores and lower PHQ-9 scores in bCBT (b=-0.030, 95% CI -0.05 to -0.01; P=.005). CONCLUSIONS: To our knowledge, this is the first study to show that bCBT may enhance the client working alliance when compared to evidence-based routine care for depression that services reported offering. The working alliance in bCBT was also associated with clinical improvements that appear to be enhanced by good program usability. Our findings add further weight to the view that the addition of internet-delivered CBT to face-to-face CBT may positively augment experiences of the working alliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02542891, https://clinicaltrials.gov/study/NCT02542891; German Clinical Trials Register DRKS00006866, https://drks.de/search/en/trial/DRKS00006866; Netherlands Trials Register NTR4962, https://www.onderzoekmetmensen.nl/en/trial/25452; ClinicalTrials.Gov NCT02389660, https://clinicaltrials.gov/study/NCT02389660; ClinicalTrials.gov NCT02361684, https://clinicaltrials.gov/study/NCT02361684; ClinicalTrials.gov NCT02449447, https://clinicaltrials.gov/study/NCT02449447; ClinicalTrials.gov NCT02410616, https://clinicaltrials.gov/study/NCT02410616; ISRCTN Registry ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725?q=ISRCTN12388725&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10; ClinicalTrials.gov NCT02796573, https://classic.clinicaltrials.gov/ct2/show/NCT02796573. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-016-1511-1.

'Does it matter how old I feel?' The role of subjective age in a psychosocial intervention for improving depressive symptomatology among older adults in Brazil (PROACTIVE).

OBJECTIVES: Depression is a prevalent mental health condition that also often affects older adults. The PROACTIVE psychosocial intervention was developed to reduce depressive symptomatology among older adults within primary care settings in Brazil. An important psychological marker that affects individuals' aging experience relates to how old people feel. Known as subjective age, this marker has been shown to be a risk factor for experiencing greater depressive symptoms if individuals report feeling older than their (chronological) age. In this study, we perform secondary analyses of the PROACTIVE cluster-randomized controlled trial to examine the role of subjective age. METHOD: The sample included 715 Brazilian older adults (74% female, Mage 68.6, SD = 6.9, age range: 60-94 years) randomized to intervention (n = 360, 74% female, Mage 68.4, SD = 6.6, age range: 60-89 years) or control (n = 355, 74% female, Mage 68.9, SD = 7.2, age range: 60-94 years) arms. Here our primary outcome was depressive symptoms at the 8-month follow-up assessed with the 9-item Patient Health Questionnaire (PHQ-9) as a continuous variable. Our previous analyses demonstrated improved recovery from depression at follow-up in the intervention compared with the control arm. RESULTS: Relevant main effects and interactions in regression models for PHQ-9 presented here found that those reporting older subjective age had worse depressive symptoms at follow-up but that they benefitted more from the intervention when initial levels of depression were high. For participants who reported younger subjective ages the intervention showed positive effects that were independent of initial levels of depression. CONCLUSION: Our findings emphasize the importance of investigating possible underlying mechanisms that can help clarify the impact of mental health interventions.

Self-help mobile messaging intervention for depression among older adults in resource-limited settings: a randomized controlled trial.

Scalable solutions to treat depression in older adults in low-resourced settings are urgently needed. The PRODIGITAL-D pragmatic, single-blind, two-arm, individually randomized controlled trial assessed the effectiveness of a mobile messaging psychosocial intervention in improving depressive symptomatology among older adults in socioeconomically deprived areas of Guarulhos, Brazil. Older adults (aged 60+ years) registered with 24 primary care clinics and identified with depressive symptomatology (9-item Patient Health Questionnaire (PHQ-9) scores ≥ 10) received the 6-week Viva Vida intervention based on psychoeducation and behavioral activation (n = 298) or a single message (n = 305). No health professional support was offered. The primary outcome was improvement from depressive symptomatology (PHQ-9 < 10) at 3 months. Of the 603 participants enrolled (mean age = 65.1 years; 451 (74.8%) women), 527 (87.4%) completed the follow-up assessment. In the intervention arm, 109 of 257 (42.4%) participants had an improved depressive symptomatology, compared with 87 of 270 (32.2%) participants in the control arm (adjusted odds ratio = 1.57; 95% confidence interval = 1.07-2.29; P = 0.019). No severe adverse events related to trial participation were observed. These results demonstrate the usefulness of a digital messaging psychosocial intervention in the short-term improvement from depressive symptomatology that can potentially be integrated into primary care programs for treating older adults with depression. Brazilian Registry of Clinical Trials registration: ReBEC ( RBR-4c94dtn ).

Do baseline characteristics affect depressive symptoms treatment success? Posthoc subgroup analysis from the CONEMO.

OBJECTIVE: As a secondary trial plan analysis, we aim to examine whether participant characteristics, measured before randomization, modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO - Emotional Control) on recovery from depression that has presented a substantive impact on previous research. METHOD: Mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest, including suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension). We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. RESULTS: Increased effects of the CONEMO intervention on the primary outcome (reduction of the scores of depressive symptoms in at least 50% at three-month follow-up) were observed amongst older and wealthier participants in Lima (p-values 0.030 and 0.001, respectively). At the same time, there was no evidence of such differential effects in São Paulo or any other secondary outcomes level in both countries. CONCLUSIONS: Digital intervention used in primary care settings needs to be accessible. We conclude that the technological intervention CONEMO has no heterogeneity effects on most subgroups studied, except income and age in the Lima trial.

Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: Rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa.

AIMS: Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the 'Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)' study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. METHODS: This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. RESULTS: The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. CONCLUSIONS: By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.

Piloting a mental health intervention for young adults in poverty enrolled in post-secondary education in post-conflict regions in Colombia: a study protocol.

Background: Colombia has endured more than five decades of internal armed conflict, which led to substantial costs for human capital and mental health. There is currently little evidence about the impact of incorporating a mental health intervention within an existing public cash transfer program to address poverty, and this project aims to develop and pilot a mental health support intervention embedded within the human capital program to achieve better outcomes among beneficiaries, especially those displaced by conflict and the most socioeconomically vulnerable. Methods: The study will consist of three phases: semi-structured one-to-one interviews, co-design and adaptations of the proposed intervention with participants and pilot of the digital intervention based on cognitive behavioral therapy and transdiagnostic techniques to determine its feasibility, acceptability, efficacy, and usefulness in 'real settings'. Results will inform if the intervention improves clinical, educational and employment prospects among those who use it. Results: Knowledge will be generated on whether the mental health intervention could potentially improve young people's mental health and human capital in conflict-affected areas? We will evaluate of the impact of potential mental health improvements on human capital outcomes, including educational and employment outcomes. Conclusion: Findings will help to make conclusions about the feasibility and acceptability of the intervention, and it will assess its effectiveness to improve the mental health and human capital outcomes of beneficiaries. This will enable the identification of strategies to address mental health problems among socioeconomically vulnerable young people that can be adapted to different contexts in in low and middle-income countries.

Digital interventions for common mental disorders in low- and middle-income countries: A systematic review and meta-analysis.

Background: In low-resource settings, e-mental health may substantially increase access to evidence-based interventions for common mental disorders. We conducted a systematic literature search to identify randomised trials examining the effects of digital interventions with or without therapeutic guidance compared to control conditions in individuals with anxiety and/or depression symptoms in low- and middle-income countries (LMICs). Methods: The main outcome was the reduction in symptoms at the post-test. Secondary outcomes included improvements in quality of life and longer-term effects (≥20 weeks post-randomisation). The effect size Hedges' g was calculated using the random effects model. Results: A total of 21 studies (23 comparisons) with 5.296 participants were included. Digital interventions were more effective than controls in reducing symptoms of common mental disorders at the post-test (g = -0.89, 95% confidence interval [CI] -1.26 to -0.52, p < 0.001; NNT = 2.91). These significant effects were confirmed when examining depressive (g = -0.77, 95% CI -1.11; -0.44) and anxiety symptoms separately (g = -1.02, 95% CI -1.53 to -0.52) and across all other sensitivity analyses. Digital interventions also resulted in a small but significant effect in improving quality of life (g = 0.32, 95% CI 0.19 to 0.45) at the post-test. Over the longer term, the effects were smaller but remained significant for all examined outcomes. Heterogeneity was moderate to high in all analyses. Subgroup and meta-regression analyses did not result in significant outcomes in any of the examined variables (e.g., guided vs. unguided interventions). Conclusions: Digital interventions, with or without guidance, may effectively bridge the gap between treatment supply and demand in LMICs. Nevertheless, more studies are needed to draw firm conclusions regarding the magnitude of the effects of digital interventions.

Potential mechanisms by which cash transfer programmes could improve the mental health and life chances of young people: A conceptual framework and lines of enquiry for research and policy.

Mental health is inextricably linked to both poverty and future life chances such as education, skills, labour market attachment and social function. Poverty can lead to poorer mental health, which reduces opportunities and increases the risk of lifetime poverty. Cash transfer programmes are one of the most common strategies to reduce poverty and now reach substantial proportions of populations living in low- and middle-income countries. Because of their rapid expansion in response to the COVID-19 pandemic, they have recently gained even more importance. Recently, there have been suggestions that these cash transfers might improve youth mental health, disrupting the cycle of disadvantage at a critical period of life. Here, we present a conceptual framework describing potential mechanisms by which cash transfer programmes could improve the mental health and life chances of young people. Furthermore, we explore how theories from behavioural economics and cognitive psychology could be used to more specifically target these mechanisms and optimise the impact of cash transfers on youth mental health and life chances. Based on this, we identify several lines of enquiry and action for future research and policy.

Patient Health Questionnaire-9 Item Pairing Predictiveness for Prescreening Depressive Symptomatology: Machine Learning Analysis.

BACKGROUND: Anhedonia and depressed mood are considered the cardinal symptoms of major depressive disorder. These are the first 2 items of the Patient Health Questionnaire (PHQ)-9 and comprise the ultrabrief PHQ-2 used for prescreening depressive symptomatology. The prescreening performance of alternative PHQ-9 item pairings is rarely compared with that of the PHQ-2. OBJECTIVE: This study aims to use machine learning (ML) with the PHQ-9 items to identify and validate the most predictive 2-item depressive symptomatology ultrabrief questionnaire and to test the generalizability of the best pairings found on the primary data set, with 6 external data sets from different populations to validate their use as prescreening instruments. METHODS: All 36 possible PHQ-9 item pairings (each yielding scores of 0-6) were investigated using ML-based methods with logistic regression models. Their performances were evaluated based on the classification of depressive symptomatology, defined as PHQ-9 scores ≥10. This gave each pairing an equal opportunity and avoided any bias in item pairing selection. RESULTS: The ML-based PHQ-9 items 2 and 4 (phq2&4), the depressed mood and low-energy item pairing, and PHQ-9 items 2 and 8 (phq2&8), the depressed mood and psychomotor retardation or agitation item pairing, were found to be the best on the primary data set training split. They generalized well on the primary data set test split with area under the curves (AUCs) of 0.954 and 0.946, respectively, compared with an AUC of 0.942 for the PHQ-2. The phq2&4 had a higher AUC than the PHQ-2 on all 6 external data sets, and the phq2&8 had a higher AUC than the PHQ-2 on 3 data sets. The phq2&4 had the highest Youden index (an unweighted average of sensitivity and specificity) on 2 external data sets, and the phq2&8 had the highest Youden index on another 2. The PHQ-2≥2 cutoff also had the highest Youden index on 2 external data sets, joint highest with the phq2&4 on 1, but its performance fluctuated the most. The PHQ-2≥3 cutoff had the highest Youden index on 1 external data set. The sensitivity and specificity achieved by the phq2&4 and phq2&8 were more evenly balanced than the PHQ-2≥2 and ≥3 cutoffs. CONCLUSIONS: The PHQ-2 did not prove to be a more effective prescreening instrument when compared with other PHQ-9 item pairings. Evaluating all item pairings showed that, compared with alternative partner items, the anhedonia item underperformed alongside the depressed mood item. This suggests that the inclusion of anhedonia as a core symptom of depression and its presence in ultrabrief questionnaires may be incompatible with the empirical evidence. The use of the PHQ-2 to prescreen for depressive symptomatology could result in a greater number of misclassifications than alternative item pairings.

Working alliance in low-intensity internet-based cognitive behavioral therapy for depression in primary care in Spain: A qualitative study.

Introduction: Psychotherapies delivered via the Internet have been promoted as an alternative for improving access to psychological treatments. A conceptual working alliance model of blended (i.e., traditional face-to-face consultation combined with Internet-delivered psychotherapy) cognitive-behavioral therapy (b-CBT) for depression has been developed in the UK. However, little is known about how this important therapeutic process, namely the working alliance (WA), is developed and maintained in Internet-delivered cognitive-behavioral therapy without face-to-face consultation (i-CBT). The aim of this study was to evaluate the validity of the WA model of b-CBT in Spanish patients with depression receiving i-CBT. Methods: Forty-one patients suffering from mild-moderate depression were interviewed to assess their experiences of an i-CBT program. Interviews were conducted with participants who received a self-guided application (n = 9), and low-intensity support (n = 10). Three group interviews were also conducted with patients who either did not start the program (n = 8) or did not complete it (n = 6), and with patients who did complete it (n = 8). Results: Qualitative thematic content analysis was performed using the constant comparative method, which revealed four main themes: "bond," "goals," "task," and "usability heuristics," all consistent with the existing literature. However, a new subcategory emerged, called "anonymity," which may highlight the social stigma that mental illness still has in the Spanish context. Conclusion: Results suggest that the development and maintenance of the WA through i-CBT could offer a better experience of the therapeutic process and improve the clinical impact. Clinical Trial Registration: Clinicaltrials.gov, identifier: NCT01611818.

Validation of the Spanish version of the Pediatric Symptom Checklist (PSC) to identify and assess psychosocial problems among early adolescents in Chile.

BACKGROUND: The high prevalence of mental disorders in early adolescents, and their consequences, encourage the need for validated instruments to identify and assess psychosocial problems. OBJECTIVES: i) To evaluate the psychometric properties of the Spanish version of the Pediatric Symptom Checklist (PSC) questionnaires (PSC-Y, 35 items, and PSC-17-Y) and its subscales (Attention, Internalizing and Externalizing subscales), including the assessment of the item structure, concurrent validity, and reliability; and ii) To assess possible associations between bullying experiences, school climate and school membership with psychological problems identified by the PSC questionnaire. METHODS: A cross-sectional study was carried out in 39 schools in Santiago, Chile. The sample consisted of 3,968 adolescents aged between 10 and 11 years. A descriptive analysis of the Pediatric Symptom Checklist was performed along with measures of dimensionality, reliability, and correlations with a validated questionnaire exploring similar constructs, the Strengths and Difficulties Questionnaire. Finally, associations of bullying, school climate, and school membership with the three subscales of the PSC were explored. RESULTS: Both versions of PSC had problems with item #7 (Act as if driven by motor), which did not load in any of the latent factors. It was removed from later analyses. The three-factor structure of PSC was confirmed. All remaining items had high factor loadings in their corresponded latent factors, and the reliability was high for the total scales (PSC-34-Y, ω = 0.78; PSC-16-Y, ω = 0.94) and the subscales of PSC-16-Y (Attention, ω = 0.77; Internalizing, ω = 0.79; Externalizing, ω = 0.78). The goodness of fit was adequate, and the correlation between PSC subscales and SDQ subscales was high. Victimization and perpetration were associated with all PSC subscales, and higher school climate and stronger school memberships were negatively associated with PSC symptoms. CONCLUSIONS: The current findings seem to demonstrate that the Spanish version of the PSC is a valid and reliable instrument for identifying and assessing psychosocial problems in early adolescents.

Use of WhatsApp by older adults screened for depression in socioeconomically deprived areas of Guarulhos, São Paulo State, Brazil: challenges and possibilities for telehealth.

This study aimed to investigate the relationship between sociodemographic characteristics, depressive symptomatology, mobile phone ownership, and different uses of WhatsApp among older adults enrolled in primary care clinics in Guarulhos, São Paulo State, Brazil. This is a secondary data analysis, using data collected in the screening of participants to be included in the PROACTIVE cluster randomized trial. Individuals aged ≥ 60 years, registered in primary care clinics in Guarulhos, were assessed for sociodemographic characteristics, depressive symptoms according to the PHQ-9, mobile phone ownership, and use of WhatsApp. We performed multiple logistic regression models to investigate characteristics of the potential users of digital interventions. Of 3,356 older adults screened for depression, 45.7% said they use WhatsApp to receive/send messages. In the subsample that presented depressive symptomatology (n = 1,020), 41.9% stated using WhatsApp. Younger older adults and those with better socioeconomic status used more WhatsApp and were more likely to own a mobile phone. Participants with higher levels of symptoms of depression were less likely to use WhatsApp. Gender, age, schooling level, income, and depressive symptomatology are variables associated with the possession of a cell phone and with the use of WhatsApp by the older adults of the sample. These findings can help to implement digital health programs better suited to disadvantaged populations in Brazil and other low- and middle-income countries through mental telehealth interventions using WhatsApp and mobile health services to the older people.

Understanding the effects of a complex psychological intervention on symptoms of depression in Goa, India: findings from a causal mediation analysis.

BACKGROUND: Understanding how and under what circumstances a highly effective psychological intervention, improved symptoms of depression is important to maximise its clinical effectiveness. AIMS: To address this complexity, we estimate the indirect effects of potentially important mediators to improve symptoms of depression (measured with the Patient Health Questionnaire (PHQ-9)) in the Healthy Activity Program trial. METHOD: Interventional in(direct) effects were used to decompose the total effect of the intervention on PHQ-9 scores into the direct and indirect effects. The following indirect effects were considered: characteristics of sessions, represented by the number of sessions and homework completed; behavioural activation, according to an adapted version of the Behavioural Activation for Depression Scale - Short Form; and extra sessions offered to participants who did not respond to the intervention. RESULTS: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.1, bias-corrected 95% CI -3.2 to -1.5), 34% was mediated through improved levels of behavioural activation (mean difference: -0.7, bias-corrected 95% CI -1.2 to -0.4). There was no evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment. CONCLUSIONS: Findings from our robust mediation analyses confirmed the importance of targeting behavioural activation. Contrary to published literature, our findings suggest that neither the number of sessions nor proportion of homework completed improved outcomes. Moreover, in this context, alternative treatments other than extra sessions should be considered for patients who do not respond to the intervention.

A peer-facilitated psychological group intervention for perinatal women living with HIV and depression in Tanzania-Healthy Options: A cluster-randomized controlled trial.

BACKGROUND: Perinatal women living with HIV (PWLH) have a greater risk of depression compared to other women; however, there are limited specialized mental health services available to them. We aimed to determine whether a stepped-care intervention facilitated by trained lay providers can improve mental health outcomes postpartum for PWLH. METHODS AND FINDINGS: Healthy Options is a cluster-randomized controlled study conducted in 16 government-managed antenatal care clinics that provided HIV care for pregnant women in urban Tanzania. Recruitment occurred from May 2015 through April 2016, with the final round of data collection completed in October 2017. Participants included a consecutive sample of pregnant women under 30 weeks of gestation, living with HIV and depression, and attending the study clinics. Control sites received enhanced usual care for depression (EUDC). Intervention sites received EUDC plus the Healthy Options intervention, which includes prenatal group sessions of problem-solving therapy (PST) plus cognitive behavioral therapy (CBT) sessions for individuals showing depressive symptoms at 6 weeks postdelivery. We assessed depressive symptoms comparable to major depressive disorder (MDD) using the Patient Health Questionnaire-9 (PHQ-9) with a locally validated cutoff at 9 months and 6 weeks postpartum. The primary time point is 9 months postpartum. We examined differences in outcomes using an intent-to-treat analysis with a complete case approach, meaning those with data at the relevant time point were included in the analysis. We used generalized estimating equations accounting for clustering. Of 818 women screened using the PHQ-9, 742 were determined eligible and enrolled (395 intervention; 347 control); 649 women (87.5%) participated in the first follow-up and 641 women (86.4%) in the second. A majority (270, 74.6%) of women in the intervention arm attended 5 or more PST sessions. Women enrolled in Healthy Options demonstrated a 67% (RR 0.33; 95% CI: 0.22, 0.51; p-value: <0.001; corresponding to a 25.7% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters at 6 weeks postpartum. At 9 months postpartum, women enrolled in Healthy Options demonstrated a nonsignificant 26% (RR 0.74; 95% CI: 0.42, 1.3; p-value: 0.281; corresponding to a 3.2% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters. Study limitations include not using diagnostic interviews to measure depression and not blinding data collectors to intervention status during follow-up. CONCLUSIONS: The Healthy Options intervention did not demonstrate reduction in depressive symptoms at 9 months postpartum, the primary outcome. Significant reductions were seen in depression symptoms at 6 weeks postpartum, the secondary outcome. Stepped-care interventions may be relevant for improving outcomes in the critical early postpartum window. TRIAL REGISTRATION: Clinical Trial registration number (closed to new participants) NCT02039973.

The effectiveness of a tablet-based video game that stimulates cognitive, emotional, and social skills in developing academic skills among preschoolers: study protocol for a randomized controlled trial.

BACKGROUND: Evidence suggests that children from low-income families begin the preschool stage with less academic and non-academic skills development compared to higher-income families. There are several successful experiences of early stimulation of cognitive and social-emotional skills; however, there is scarce evidence of the effectiveness of a video game that incorporates the stimulation of these skills simultaneously. This study aims to evaluate the effectiveness of a video game in stimulating cognitive, emotional, and social competence skills in developing academic skills in socioeconomically disadvantaged preschool children. METHODS: A cluster-randomized controlled trial design will be used. A tablet-based video game that stimulates cognitive and socio-emotional skills to improve the development of academic skills is compared with a tablet-based game where students draw and paint with no explicit stimulation of cognitive and socio-emotional skills. Eighteen schools and 750 Chilean preschool students will be recruited. The effectiveness of the intervention will be assessed using a direct evaluation of children on literacy learning and pre-calculation skills at baseline, immediately after stimulation, and at 6, 12, 18, and 24 months post-intervention. The mediating effect of working memory, inhibitory control, emotion recognition, and prosocial behaviours will be assessed on the effectiveness of the intervention. DISCUSSION: The proposed study will be the first to test the effectiveness of a tablet-based video game stimulating cognitive and social-emotional skills to improve academic skills in socioeconomically disadvantaged preschool children in Chile, controlling for gender, age (in months), mental health, and baseline conditions of stimulated skills. TRIAL REGISTRATION: ClinicalTrials.gov NCT05224700. Registered on February 2022.

Using the RE-AIM framework to evaluate the implementation of scaling-up the Friendship Bench in Zimbabwe - a quantitative observational study.

BACKGROUND: This study aimed to evaluate the real-world implementation of the Friendship Bench (FB) - an evidence-based brief psychological intervention delivered by community health workers (CHWs) - three years after its implementation in three city health departments in Zimbabwe. Implementation sites were evaluated according to their current performance using the RE-AIM framework making this one of the first evaluations of a scaled-up evidence-based psychological intervention in sub-Saharan Africa (SSA). METHODS: Using the RE-AIM guide ( www.re-aim.org ), the authors designed quantitative indicators based on existing FB implementation data. Thirty-six primary health care clinics (PHC) in Harare (n=28), Chitungwiza (n=4) and Gweru (n=4) were included. Among these clinics 20 were large comprehensive health care centers, 7 medium (mostly maternal and child healthcare) and 9 small clinics (basic medical care and acting as referral clinic). Existing data from these clinics, added to additionally collected data through interviews and field observations were used to investigate and compare the performance of the FB across clinics. The focus was on the RE-AIM domains of Reach, Adoption, and Implementation. RESULTS: Small clinics achieved 34% reach, compared to large (15%) and medium clinics (9%). Adoption was high in all clinic types, ranging from 59% to 71%. Small clinics led the implementation domain with 53%, followed by medium sized clinics 43% and large clinics 40%. Small clinics performed better in all indicators and differences in performance between small and large clinics were significant. Program activity and data quality depends on ongoing support for delivering agents and buy-in from health authorities. CONCLUSION: The Friendship Bench program was implemented over three years transitioning from a research-based implementation program to one led locally. The Reach domain showed the largest gap across clinics where larger clinics performed poorly relative to smaller clinics and should be a target for future implementation improvements. Program data needs to be integrated into existing health information systems. Future studies should seek to optimize scale-up and sustainment strategies to maintain effective task-shared psychological interventions in SSA.

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic resource for aquaculture.

The European flat oyster (Ostrea edulis L.) is a native bivalve of the European coasts. Harvest of this species has declined during the last decades because of the appearance of two parasites that have led to the collapse of the stocks and the loss of the natural oyster beds. O. edulis has been the subject of numerous studies in population genetics and on the detection of the parasites Bonamia ostreae and Marteilia refringens. These studies investigated immune responses to these parasites at the molecular and cellular levels. Several genetic improvement programs have been initiated especially for parasite resistance. Within the framework of a European project (PERLE 2) that aims to produce genetic lines of O. edulis with hardiness traits (growth, survival, resistance) for the purpose of repopulating natural oyster beds in Brittany and reviving the culture of this species in the foreshore, obtaining a reference genome becomes essential as done recently in many bivalve species of aquaculture interest. Here, we present a chromosome-level genome assembly and annotation for the European flat oyster, generated by combining PacBio, Illumina, 10X linked, and Hi-C sequencing. The finished assembly is 887.2 Mb with a scaffold-N50 of 97.1 Mb scaffolded on the expected 10 pseudochromosomes. Annotation of the genome revealed the presence of 35,962 protein-coding genes. We analyzed in detail the transposable element (TE) diversity in the flat oyster genome, highlighted some specificities in tRNA and miRNA composition, and provided the first insight into the molecular response of O. edulis to M. refringens. This genome provides a reference for genomic studies on O. edulis to better understand its basic physiology and as a useful resource for genetic breeding in support of aquaculture and natural reef restoration.

A task-shared, collaborative care psychosocial intervention for improving depressive symptomatology among older adults in a socioeconomically deprived area of Brazil (PROACTIVE): a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial.

BACKGROUND: There is an urgent need to reduce the burden of depression among older adults in low-income and middle-income countries (LMICs). We aimed to evaluate the efficacy of a task-shared, collaborative care psychosocial intervention for improving recovery from depression in older adults in Brazil. METHODS: PROACTIVE was a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial conducted in Guarulhos, Brazil. Primary care clinics (clusters) were stratified by educational level and randomly allocated (1:1) to either enhanced usual care alone (control group) or to enhanced usual care plus the psychosocial intervention (intervention group), which involved a 17-week psychosocial programme based on psychoeducation and behavioural activation approaches. Individuals approached for the initial screening assessment were selected randomly from a list of individuals provided by the Health Secretariat of Guarulhos. Face-to-face baseline assessments were conducted among adults aged 60 years or older registered with one of the primary care clinics and identified with clinically significant depressive symptomatology (9-item Patient Health Questionnaire [PHQ-9] score ≥10). Community health workers delivered the programme through home sessions, supported by a dedicated tablet application. Masking of clinic staff and community health workers who delivered the intervention was not feasible; however, research assistants conducting recruitment and follow-up assessments were masked to trial allocation. The primary outcome was recovery from depression (PHQ-9 score <10) at 8-month follow-up. All primary analyses were performed by intention to treat with imputed data. Adaptations to the protocol were made due to the COVID-19 pandemic; recruitment and intervention home sessions were stopped, and follow-up assessments were conducted by telephone. This trial is registered with the ISRCTN registry, ISRCTN57805470. FINDINGS: We identified 24 primary care clinics in Guarulhos that were willing to participate, of which 20 were randomly allocated to either the control group (ten [50%] clusters) or to the intervention group (ten [50%] clusters). The four remaining eligible clusters were kept as reserves. Between May 23, 2019, and Feb 21, 2020, 8146 individuals were assessed for eligibility, of whom 715 (8·8%) participants were recruited: 355 (49·7%) in the control group and 360 (50·3%) in the intervention group. 284 (80·0%) participants in the control group and 253 (70·3%) in the intervention group completed follow-up at 8 months. At 8-month follow-up, 158 (62·5%) participants in the intervention group showed recovery from depression (PHQ-9 score <10) compared with 125 (44·0%) in the control group (adjusted odds ratio 2·16 [95% CI 1·47-3·18]; p<0·0001). These findings were maintained in the complete case analysis. No adverse events related to the intervention were observed. INTERPRETATION: Although the COVID-19 pandemic altered delivery of the intervention, the low-intensity psychosocial intervention delivered mainly by non-mental health professionals was highly efficacious in improving recovery from depression in older adults in Brazil. Our results support a low-resource intervention that could be useful to reduce the treatment gap for depression among older people in other LMICs. FUNDING: São Paulo Research Foundation and Joint Global Health Trials (UK Department for International Development, Medical Research Council, and the Wellcome Trust).

Participants' and Nurses' Experiences With a Digital Intervention for Patients With Depressive Symptoms and Comorbid Hypertension or Diabetes in Peru: Qualitative Post-Randomized Controlled Trial Study.

BACKGROUND: Depression is one of the most prevalent mental disorders and a leading cause of disability, disproportionately affecting specific groups, such as patients with noncommunicable diseases. Over the past decade, digital interventions have been developed to provide treatment for these patients. CONEMO (Emotional Control in Spanish) is an 18-session psychoeducational digital intervention delivered through a smartphone app and minimally supported by a nurse. CONEMO demonstrated effectiveness in reducing depressive symptoms through a randomized controlled trial (RCT) among patients with diabetes, hypertension, or both, in Lima, Peru. However, in addition to clinical outcomes, it is important to explore users' experiences, satisfaction, and perceptions of usability and acceptability, which can affect their engagement with the intervention. OBJECTIVE: This study aimed to explore the RCT participants' experiences with CONEMO in Peru, complemented with information provided by the nurses who monitored them. METHODS: In 2018, semistructured interviews were conducted with a sample of 29 (13.4%) patients from the 217 patients who participated in the CONEMO intervention in Peru and the 3 hired nurses who supported its delivery. Interviewees were selected at random based on their adherence to the digital intervention (0-5, 10-14, and 15-18 sessions completed), to include different points of view. Content analysis was conducted to analyze the interviews. RESULTS: Participants' mean age was 64.4 (SD 8.5) years, and 79% (23/29) of them were women. Most of the interviewed participants (21/29, 72%) stated that CONEMO fulfilled their expectations and identified positive changes in their physical and mental health after using it. Some of these improvements were related to their thoughts and feelings (eg, think differently, be more optimistic, and feel calmer), whereas others were related to their routines (eg, go out more and improve health-related habits). Most participants (19/29, 66%) reported not having previous experience with using smartphones, and despite experiencing some initial difficulties, they managed to use CONEMO. The most valued features of the app were the videos and activities proposed for the participant to perform. Most participants (27/29, 93%) had a good opinion about the study nurses and reported feeling supported by them. A few participants provided suggestions to improve the intervention, which included adding more videos, making the sessions' text simple, extending the length of the intervention, and improving the training session with long explanations. CONCLUSIONS: The findings of this qualitative study provide further support and contextualize the positive results found in the CONEMO RCT, including insights into the key features that made the intervention effective and engaging. The participants' experience with the smartphone and CONEMO app reveal that it is feasible to be used by people with little knowledge of technology. In addition, the study identified suggestions to improve the CONEMO intervention for its future scale-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT03026426; https://clinicaltrials.gov/ct2/show/NCT03026426.