Association between tuberculosis and psychotic experiences: Mediating factors and implications for patient care in low- and middle-income countries.

Background: Tuberculosis may play a role in the aetiology of psychosis. However, little is known about the association between tuberculosis and psychotic experiences (PEs) or the mediating factors of this association. Methods: We analysed cross-sectional data from 48 low- and middle-income countries of the World Health Survey (WHS). Tuberculosis assessment was based on past 12-month symptoms of active tuberculosis. We assessed four types of past 12-month PEs with the Composite International Diagnostic Interview. We performed multivariable multinomial logistic regression and mediation analysis. Results: We analysed data on 224 842 individuals aged ≥18 years (mean age = 38.3 years, standard deviation = 16.0; 50.7% women). Tuberculosis was associated with 1.84 (95% confidence interval (CI) = 1.41-2.40), 2.18 (95%CI = 1.58-3.03), and 3.79 (95%CI = 2.88-4.98) times higher odds for 1, 2, and ≥3 PEs, respectively. The mediation analysis showed that the association between tuberculosis and at least one PE is mainly explained by anxiety (31.5%), sleep/energy (27.8%), and pain/discomfort (23.5%). Conclusions: Tuberculosis was associated with increased odds of PEs. Factors such as affect, sleep, and pain should be considered in tuberculosis patients to target those who might be particularly vulnerable to PEs, and consequently, to psychotic disorders and other adverse effects of PE.

Effectiveness of a mental health stepped-care programme for healthcare workers with psychological distress in crisis settings: a multicentre randomised controlled trial.

BACKGROUND: Evidence-based mental health interventions to support healthcare workers (HCWs) in crisis settings are scarce. OBJECTIVE: To evaluate the capacity of a mental health intervention in reducing anxiety and depression symptoms in HCWs, relative to enhanced care as usual (eCAU), amidst the COVID-19 pandemic. METHODS: We conducted an analyst-blind, parallel, multicentre, randomised controlled trial. We recruited HCWs with psychological distress from Madrid and Catalonia (Spain). The intervention arm received a stepped-care programme consisting of two WHO-developed interventions adapted for HCWs: Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+). Each intervention lasted 5 weeks and was delivered remotely by non-specialist mental health providers. HCWs reporting psychological distress after DWM completion were invited to continue to PM+. The primary endpoint was self-reported anxiety/depression symptoms (Patient Health Questionnaire-Anxiety and Depression Scale) at week 21. FINDINGS: Between 3 November 2021 and 31 March 2022, 115 participants were randomised to stepped care and 117 to eCAU (86% women, mean age 37.5). The intervention showed a greater decrease in anxiety/depression symptoms compared with eCAU at the primary endpoint (baseline-adjusted difference 4.4, 95% CI 2.1 to 6.7; standardised effect size 0.8, 95% CI 0.4 to 1.2). No serious adverse events occurred. CONCLUSIONS: Brief stepped-care psychological interventions reduce anxiety and depression during a period of stress among HCWs. CLINICAL IMPLICATIONS: Our results can inform policies and actions to protect the mental health of HCWs during major health crises and are potentially rapidly replicable in other settings where workers are affected by global emergencies. TRIAL REGISTRATION NUMBER: NCT04980326.

Effectiveness of a stepped-care programme of internet-based psychological interventions for healthcare workers with psychological distress: Study protocol for the RESPOND healthcare workers randomised controlled trial.

Background and aims: The coronavirus disease 2019 pandemic has challenged health services worldwide, with a worsening of healthcare workers' mental health within initial pandemic hotspots. In early 2022, the Omicron variant is spreading rapidly around the world. This study explores the effectiveness and cost-effectiveness of a stepped-care programme of scalable, internet-based psychological interventions for distressed health workers on self-reported anxiety and depression symptoms. Methods: We present the study protocol for a multicentre (two sites), parallel-group (1:1 allocation ratio), analyst-blinded, superiority, randomised controlled trial. Healthcare workers with psychological distress will be allocated either to care as usual only or to care as usual plus a stepped-care programme that includes two scalable psychological interventions developed by the World Health Organization: A guided self-help stress management guide (Doing What Matters in Times of Stress) and a five-session cognitive behavioural intervention (Problem Management Plus). All participants will receive a single-session emotional support intervention, namely psychological first aid. We will include 212 participants. An intention-to-treat analysis using linear mixed models will be conducted to explore the programme's effect on anxiety and depression symptoms, as measured by the Patient Health Questionnaire - Anxiety and Depression Scale summary score at 21 weeks from baseline. Secondary outcomes include post-traumatic stress disorder symptoms, resilience, quality of life, cost impact and cost-effectiveness. Conclusions: This study is the first randomised trial that combines two World Health Organization psychological interventions tailored for health workers into one stepped-care programme. Results will inform occupational and mental health prevention, treatment, and recovery strategies. Registration details: ClinicalTrials.gov Identifier: NCT04980326.

Mental health symptoms 1 year after the COVID-19 outbreak in Spain: The role of pre-existing mental disorders and their type.

BACKGROUND: The type of pre-existing disorder might determine changes in mental health symptoms (i.e., anxiety, depression) during the COVID-19 pandemic and influence the effect of psychological factors (e.g., social support, resilience, stress) on such symptoms. METHODS: Longitudinal data from two assessments (June-2020 and February/March-2021) collected through telephone interviews (Spanish general population) were analysed. Outcome variables included anxiety (GAD-7) and depressive symptoms (PHQ-8). Psychological factors included COVID-perceived stress (adapted COVID-perceived risk scale), social support (OSSS-3), and resilience (CD-RISC). Pre-existing mental conditions (3 groups: mood, anxiety, and comorbid depression+anxiety) were assessed using the CIDI checklist. Changes in anxiety and depressive symptoms between baseline and follow-up were assessed with the paired samples Wilcoxon test. Tobit regression and interaction models were conducted to test associations between psychological factors and these symptoms in follow-up. RESULTS: Final sample included 1942 participants (mean age 49.6 yrs., ±16.7; 51.7 % females). Anxiety symptoms increased in all groups except for those with pre-existing mood conditions. Depressive symptoms only increased in those without pre-existing mental disorders and in those with pre-existing anxiety. Higher baseline resilience, increases in social support, and decreases in COVID-perceived stress were associated with lower anxiety and depressive symptoms. The type of pre-existing mental disorder did not modify these associations. LIMITATIONS: Lack of pre-pandemic data and the limited number of pre-existing mental conditions. CONCLUSIONS: Having pre-pandemic mental disorders is associated with different patterns of anxiety and depressive symptoms during the pandemic. COVID-related stress, social support, and resilience are key factors in improving mental health regardless of the mental diagnosis.

Mental health problems and needs of frontline healthcare workers during the COVID-19 pandemic in Spain: A qualitative analysis.

Background: Healthcare workers (HCWs) from COVID-19 hotspots worldwide have reported poor mental health outcomes since the pandemic's beginning. The virulence of the initial COVID-19 surge in Spain and the urgency for rapid evidence constrained early studies in their capacity to inform mental health programs accurately. Here, we used a qualitative research design to describe relevant mental health problems among frontline HCWs and explore their association with determinants and consequences and their implications for the design and implementation of mental health programs. Materials and methods: Following the Programme Design, Implementation, Monitoring, and Evaluation (DIME) protocol, we used a two-step qualitative research design to interview frontline HCWs, mental health experts, administrators, and service planners in Spain. We used Free List (FL) interviews to identify problems experienced by frontline HCWs and Key informant (KI) interviews to describe them and explore their determinants and consequences, as well as the strategies considered useful to overcome these problems. We used a thematic analysis approach to analyze the interview outputs and framed our results into a five-level social-ecological model (intrapersonal, interpersonal, organizational, community, and public health). Results: We recruited 75 FL and 22 KI interviewees, roughly balanced in age and gender. We detected 56 themes during the FL interviews and explored the following themes in the KI interviews: fear of infection, psychological distress, stress, moral distress, and interpersonal conflicts among coworkers. We found that interviewees reported perceived causes and consequences across problems at all levels (intrapersonal to public health). Although several mental health strategies were implemented (especially at an intrapersonal and interpersonal level), most mental health needs remained unmet, especially at the organizational, community, and public policy levels. Conclusions: In keeping with available quantitative evidence, our findings show that mental health problems are still relevant for frontline HCWs 1 year after the COVID-19 pandemic and that many reported causes of these problems are modifiable. Based on this, we offer specific recommendations to design and implement mental health strategies and recommend using transdiagnostic, low-intensity, scalable psychological interventions contextually adapted and tailored for HCWs.

Methods for Stratification and Validation Cohorts: A Scoping Review.

Personalized medicine requires large cohorts for patient stratification and validation of patient clustering. However, standards and harmonized practices on the methods and tools to be used for the design and management of cohorts in personalized medicine remain to be defined. This study aims to describe the current state-of-the-art in this area. A scoping review was conducted searching in PubMed, EMBASE, Web of Science, Psycinfo and Cochrane Library for reviews about tools and methods related to cohorts used in personalized medicine. The search focused on cancer, stroke and Alzheimer's disease and was limited to reports in English, French, German, Italian and Spanish published from 2005 to April 2020. The screening process was reported through a PRISMA flowchart. Fifty reviews were included, mostly including information about how data were generated (25/50) and about tools used for data management and analysis (24/50). No direct information was found about the quality of data and the requirements to monitor associated clinical data. A scarcity of information and standards was found in specific areas such as sample size calculation. With this information, comprehensive guidelines could be developed in the future to improve the reproducibility and robustness in the design and management of cohorts in personalized medicine studies.

The impact of COVID-related perceived stress and social support on generalized anxiety and major depressive disorders: moderating effects of pre-pandemic mental disorders.

BACKGROUND: We assessed the moderating effect of pre-pandemic mental disorders on the association of COVID-related perceived stress and social support with mental health. METHODS: A nationally representative sample of 3500 Spanish adults was interviewed in June 2020 (mean age 49.25 years, ± 15.64; 51.50% females). Mental health included Generalized Anxiety Disorders (GAD; GAD-7, cut-off point of ≥ 10), Major Depressive Disorders (MDD; PHQ-8, cut-off point of ≥ 10) and the comorbid form (those screening positive for GAD and MDD). COVID-related stress was assessed using an adapted version of the Peri Life Events Scale, and social support using the Oslo Social Support Scale. Logistic regression models were used to assess if COVID-related stress and social support were related to mental health outcomes and interactions were conducted to examine whether these relationships differed according to the presence of pre-pandemic mental disorders. RESULTS: Higher COVID-related stress was associated with a higher risk of lower mental health. The association between COVID-related stress with GAD and MDD was significantly moderated by pre-pandemic mental disorders, except for comorbid GAD + MDD. Higher levels of social support were linked to better mental health. Only the association between social support and GAD was significantly moderated by pre-pandemic mental disorders. That is, for those without pre-pandemic mental disorders, higher levels of social support decreased the odds of GAD, while minor decreases were observed in those with pre-pandemic mental disorders. CONCLUSIONS: The impact of COVID-related stress and social support on specific indicators of mental health may vary depending on the existence of a previous mental disorder.

A systematic literature review of prognostic factors in patients with HR+/HER2- advanced breast cancer in Japan.

BACKGROUND: Breast cancer is the most prevalent cancer in women in Japan and the fifth in mortality. This systematic review summarized the evidence for prognostic factors for patients with HR+/HER2- advanced and metastatic breast cancer in Japan. METHODS: MEDLINE and EMBASE were searched with keywords 'breast neoplasms' AND 'Japan' AND 'advanced' or equivalent, and Japan Medical Abstract Society database with 'breast cancer' AND 'advanced/metastatic' for publications from January 2010 to October 2019. ASCO, ESMO, ABC4 abstracts and WHO website were hand searched. The endpoints of interest were overall survival, progression-free survival, tumour response and post-progression survival. Factors were evaluated based on the consistency in direction and the strength (hazard ratios) of association. RESULTS: Searches identified 4530 publications, of which 27 were eligible. All were observational studies. Among the endpoints, overall survival was the most commonly assessed (n = 22) and evaluated further. Ki-67 expression, progesterone receptor expression status, tumour grade and lymph node metastases were consistently associated with poor overall survival in univariate analysis but not in multivariate analysis. Short disease-free interval, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival in both of univariate and multivariate analysis. The association was strong for liver metastasis (hazard ratio ≥2.8 in the majority of studies) and moderate for disease-free interval and the number of metastatic organs (hazard ratio 1.3-2.8 in the majority of studies). CONCLUSIONS: Disease-free interval, the number of metastatic organs and liver metastasis were identified as independent prognostic factors for overall survival. These findings may help clinical decision-making to improve outcomes in patients with HR+/HER2- advanced and metastatic breast cancer.

Nutrition, Bioenergetics, and Metabolic Syndrome.

According to the World Health Organization (WHO), the global nutrition report shows that whilst part of the world's population starves, the other part suffers from obesity and associated complications. A balanced diet counterparts these extreme conditions with the proper proportion, composition, quantity, and presence of macronutrients, micronutrients, and bioactive compounds. However, little is known on the way these components exert any influence on our health. These nutrients aiming to feed our bodies, our tissues, and our cells, first need to reach mitochondria, where they are decomposed into CO2 and H2O to obtain energy. Mitochondria are the powerhouse of the cell and mainly responsible for nutrients metabolism, but they are also the main source of oxidative stress and cell death by apoptosis. Unappropriated nutrients may support mitochondrial to become the Trojan horse in the cell. This review aims to provide an approach to the role that some nutrients exert on mitochondria as a major contributor to high prevalent Western conditions including metabolic syndrome (MetS), a constellation of pathologic conditions which promotes type II diabetes and cardiovascular risk. Clinical and experimental data extracted from in vitro animal and cell models further demonstrated in patients, support the idea that a balanced diet, in a healthy lifestyle context, promotes proper bioenergetic and mitochondrial function, becoming the best medicine to prevent the onset and progression of MetS. Any advance in the prevention and management of these prevalent complications help to face these challenging global health problems, by ameliorating the quality of life of patients and reducing the associated sociosanitary burden.

Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density.

Numerous GWAS and candidate gene studies have highlighted the role of the Wnt pathway in bone biology. Our objective has been to study in detail the allelic architecture of three Wnt pathway genes: WNT16, DKK1 and SOST, in the context of osteoporosis. We have resequenced the coding and some regulatory regions of these three genes in two groups with extreme bone mineral density (BMD) (n = ∼50, each) from the BARCOS cohort. No interesting novel variants were identified. Thirteen predicted functional variants have been genotyped in the full cohort (n = 1490), and for ten of them (with MAF > 0.01), the association with BMD has been studied. We have found six variants nominally associated with BMD, of which 2 WNT16 variants predicted to be eQTLs for FAM3C (rs55710688, in the Kozak sequence and rs142005327, within a putative enhancer) withstood multiple-testing correction. In addition, two rare variants in functional regions (rs190011371 in WNT16b 3'UTR and rs570754792 in the SOST TATA box) were found only present in three women each, all with BMD below the mean of the cohort. Our results reinforce the higher importance of regulatory versus coding variants in these Wnt pathway genes and open new ways for functional studies of the relevant variants.