Implementing a psychosocial intervention DIALOG+ for patients with psychotic disorders in low and middle income countries in South Eastern Europe: protocol for a hybrid effectiveness-implementation cluster randomized clinical trial (IMPULSE)

Psychotic disorders have large treatment gap in low- and middle-income countries (LMICs) in South-Eastern Europe, where up to 45% of affected people do not receive care for their condition. This study will assess the implementation of a generic psychosocial intervention called DIALOG+ in mental health care services and its effectiveness at improving patients’ clinical and social outcomes.This is a protocol for a multi-country, pragmatic, hybrid effectiveness–implementation, cluster-randomised, clinical trial. The trial aims to recruit 80 clinicians and 400 patients across 5 South-Eastern European LMICs: Bosnia and Herzegovina, Kosovo*, Montenegro, Republic of North Macedonia and Serbia. Clusters are clinicians working with patients with psychosis, and each clinician will deliver the intervention to five patients. After patient baseline assessments, clinicians will be randomly assigned to either the DIALOG+ intervention or treatment as usual, with an allocation ratio of 1:1. The intervention will be delivered six times over 12 months during routine clinical meetings. TThe primary outcome measure is the quality of life at 12 months [Manchester Short Assessment of Quality of Life (MANSA)]; the secondary outcomes include mental health symptoms [Brief Psychiatric Rating Scale (BPRS), Clinical Assessment Interview for Negative Symptoms (CAINS), Brief Symptom Inventory (BSI)], satisfaction with services [Client Satisfaction Questionnaire (CSQ-8)] and economic costs at 12 months [based on Client Service Receipt Inventory (CSRI), EQ-5D-5L and Recovering Quality of Life (ReQOL-10)]. The study will assess the intervention fidelity and the experience of clinicians and patients’ about implementing DIALOG+ in real-life mental health care settings. In the health economic assessment, the incremental cost-effectiveness ratio is calculated with effectiveness measured by quality-adjusted life year. Data will also be collected on sustainability and reach to inform guidelines for potentially scaling up and implementing the intervention widely. Conclusion: The study is expected to generate new scientific knowledge on the treatment of people with psychosis in health care systems with limited resources. The learning from LMICs could potentially help other countries to expand the access to care and alleviate the suffering of patients with psychosis and their families. Trial registration: ISRCTN 11913964This study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779334

Cost-effectiveness of implementing a digital psychosocial intervention for patients with psychotic spectrum disorders in low- and middle-income countries in Southeast Europe: Economic evaluation alongside a cluster randomised trial

BACKGROUND: DIALOG+ is a digital psychosocial intervention aimed at making routine meetings between patients and clinicians therapeutically effective. This study aimed to evaluate the cost-effectiveness of implementing DIALOG+ treatment for patients with psychotic disorders in five low- and middle-income countries in Southeast Europe alongside a cluster randomised trial. METHODS: Resource use and quality of life data were collected alongside the multi-country cluster randomised trial of 468 participants with psychotic disorders. Due to COVID-19 interruptions of the trial’s original 12-month intervention period, adjusted costs and quality-adjusted life years (QALYs) were estimated at the participant level using a mixed-effects model over the first 6 months only. We estimated the incremental cost-effectiveness ratio (ICER) with uncertainty presented using a cost-effectiveness plane and a cost-effectiveness acceptability curve. Seven sensitivity analyses were conducted to check the robustness of the findings. RESULTS: The average cost of delivering DIALOG+ was €91.11 per participant. DIALOG+ was associated with an incremental health gain of 0.0032 QALYs (95% CI –0.0015, 0.0079), incremental costs of €84.17 (95% CI –8.18, 176.52), and an estimated ICER of €26,347.61. The probability of DIALOG+ being cost-effective against three times the weighted gross domestic product (GDP) per capita for the five participating countries was 18.9%. CONCLUSION: Evidence from the cost-effectiveness analyses in this study suggested that DIALOG+ involved relatively low costs. However, it is not likely to be cost-effective in the five participating countries compared with standard care against a willingness-to-pay threshold of three times the weighted GDP per capita per QALY gained

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

Implementing a digital mental health intervention for individuals with psychosis-a multi-country qualitative study

BACKGROUND: Implementation of psychosocial interventions in mental health services has the potential to improve the treatment of psychosis spectrum disorders (PSD) in low- and middle-income countries (LMICs) where care is predominantly focused on pharmacotherapy. The first step is to understand the views of key stakeholders. We conducted a multi-language qualitative study to explore the contextual barriers and facilitators to implementation of a cost-effective, digital psychosocial intervention, called DIALOG+, for treating PSD. DIALOG+ builds on existing clinician-patient relationships without requiring development of new services, making it well-fitting for healthcare systems with scarce resources. METHODS: Thirty-two focus groups were conducted with 174 participants (patients, clinicians, policymakers and carers), who were familiarized with DIALOG+ through a presentation. The Southeast European LMICs included in this research were: Bosnia and Herzegovina, Kosovo, (Kosovo is referred throughout the text by United Nations resolution) North Macedonia, Montenegro and Serbia. Framework analysis was used to analyse the participants’ accounts. RESULTS: Six major themes were identified. Three themes (Intervention characteristics; Carers’ involvement; Patient and organisational benefits) were interpreted as perceived implementation facilitators. The theme Attitudes and perceived preparedness of potential adopters comprised of subthemes that were interpreted as both perceived implementation facilitators and barriers. Two other themes (Frequency of intervention delivery; Suggested changes to the intervention) were more broadly related to the intervention’s implementation. Participants were exceedingly supportive of the implementation of a digital psychosocial intervention such as DIALOG+. Attractive intervention characteristics, efficient use of scarce resources for its implementation and potential to improve mental health services were seen as the main implementation facilitators. The major implementation barrier identified was psychiatrists’ time constrains. CONCLUSIONS: This study provided important insights regarding implementation of digital psychosocial interventions for people with PSD in low-resource settings by including perspectives from four stakeholder groups in five LMICs in Southeast Europe – a population and region rarely explored in the literature. The perceived limited availability of psychiatrists could be potentially resolved by increased inclusion of other mental health professionals in service delivery for PSD. These findings will be used to inform the implementation strategy of DIALOG+ across the participating countries. The study also offers insights into multi-country qualitative research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-021-03466-x

Neighborhood Socioeconomic Status in Relation to Serum Biomarkers in the Black Women’s Health Study

Lower neighborhood socioeconomic status (SES) is associated with higher cardiovascular disease (CVD) risk. Black women have a higher CVD risk and are more likely to live in poor neighborhoods than white women. We examined the association of neighborhood SES with several CVD biomarkers using data from the Black Women’s Health Study (BWHS), a follow-up study of US black women reporting high levels of education and income. Blood specimens of 418 BWHS participants were assayed for C-reactive protein (CRP), hemoglobin A1C (hgA1C), and high-density lipoprotein (HDL) cholesterol. US Census block group data were linked to the women’s addresses to reflect neighborhood SES. Multivariable-adjusted mixed linear regression models that adjusted for person-level SES and for cardiovascular risk factors were used to assess CRP, hgA1C, and HDL levels in relation to quintiles of neighborhood SES. Women living in the poorest neighborhoods had the least favorable biomarker levels. As neighborhood SES increased, CRP decreased (P for trend = 0.01), hgA1C decreased (P for trend = 0.07), and HDL increased (P for trend = 0.19). These associations were present within strata of individual educational level. The present findings suggest that neighborhood environments may affect physiological processes within residents independently of individual SES

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder A Mendelian Randomization Study

Importance: There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood. Objectives: To investigate the association of PTSD with traits related to EA. Design, Setting, and Participants: Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018. Main Outcomes and Measures: Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. Results: Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (rg = -0.26; SE = 0.05; P = 4.60 × 10-8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (β = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: β = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10-5; risk-taking: β = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10-4), while income may mediate the association of EA with PSTD (MR income: β = -0.18; 95% CI, -0.29 to -0.07; P = .001; MR EA: β = -0.23; 95% CI, -0.39 to -0.07; P = .004; multivariable MR income: β = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: β = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79). Conclusions and Relevance: Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed