Collaborative Outcomes Study on Health and Functioning During Infection Times (COH-FIT): Global and Risk-Group Stratified Course of Well-Being and Mental Health During the COVID-19 Pandemic in Adolescents.

Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide.

Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization-Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori- defined individual/cumulative risk factors were measured.

Identification and functional analysis of novel homozygous LMF1 variants in severe hypertriglyceridemia.

Background: The genetic basis of hypertriglyceridemia (HTG) is complex and includes variants in Lipase Maturation Factor 1 (LMF1), an endoplasmic reticulum (ER)-chaperone involved in the post-translational activation of lipoprotein lipase (LPL).

Objective: The objective of this study was to identify and functionally characterize biallelic LMF1 variants in patients with HTG.

Methods: Genomic DNA sequencing was used to identify biallelic LMF1 variants in HTG patients without deleterious variants in LPL, apolipoprotein C-II (APOC2), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) or apolipoprotein A-V (APOA5).

Optimization of Smoking Classification by Applying Neural Network with Variable Importance Using Cytokine Biomarkers.

Cigarette smoking is a preventable epidemic that is a leading cause of death. It increases the risk of coronary heart disease, stroke, lung cancer, chronic obstructive lung diseases etc., multifold.

Logistic Regression and Statistical Regularization Techniques for Risk Classification of Coronary Artery Disease using Cytokines transported by high density lipoproteins.

Coronary artery disease (CAD) is a leading cause of mortality in the world. It is important to be able to proactively assess the risk of the disease, using novel biomarkers like cytokines that are indicators of inflammation in addition to traditional predictors of risk. Atherosclerosis, the primary cause of CAD, is an inflammatory disease involving cytokines.

Multi-level barriers and facilitators to implementing evidence-based antipsychotics in the treatment of early-phase schizophrenia.

Introduction: Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic and clozapine use within a shared decision-making model.

Methods: Semi-structured interviews explored barriers and facilitators to implementing LAI antipsychotics and clozapine in early intervention services.

Smoking Classification Using Novel Plasma Cytokines by implementing Machine Learning and Statistical Methods.

Smoking is a major cause of premature and preventable death. Tobacco exposure has a detrimental effect on many organs and contributes to multiple diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disease, cancer, and diabetes. Cytokines are inflammatory biomarkers that are mechanistically associated with smoking.

Introducing S.C.O.P.E.™ (Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement), an Interactive Digital Platform to Educate Healthcare Professionals on Schizophrenia Care.

Despite evidence of benefits beyond those of oral antipsychotics, long-acting injectable antipsychotics (LAIs) are underused in schizophrenia treatment. Underuse may be partially a result of misconceptions held by some healthcare professionals (HCPs) pertaining to LAIs. A panel of four experts convened between January 2022 and May 2022 to identify these misconceptions, and example cases or scenarios were created to illustrate common clinical situations relevant to these beliefs.

The COMPASS scale for the assessment of individuals with first episode psychotic disorders.

Background: Psychosis symptom assessment instruments are rarely used in US mental health community clinical practice despite the advantages of measurement-based care. Barriers include the length of typical scales and that data for scale evaluation often come from researcher and not clinician raters.

Study Design: The 12-item COMPASS symptom assessment was designed for the RAISE-ETP study of early phase psychosis.

The Simultaneous Inhibition of Solute Carrier Family 6 Member 19 and Breast Cancer Resistance Protein Transporters Leads to an Increase of Indoxyl Sulfate (a Uremic Toxin) in Plasma and Kidney.

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.

A Long-Term Safety and Tolerability Study of TV-46000 for Subcutaneous Use in Patients with Schizophrenia: A Phase 3, Randomized, Double-Blinded Clinical Trial.

Background: TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. In the phase 3, randomized, double-blind RIsperidone Subcutaneous Extended-release (RISE) study, TV-46000 once monthly (q1m) and once every 2 months (q2m) significantly prolonged time to impending relapse compared with placebo [5.0-fold (q1m) and 2.

A genetic cross reveals the contributions of and to piperaquine drug resistance.

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the () and increased copies of (). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31).

Identification of Selective Imidazopyridine CSF1R Inhibitors.

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors.

Antipsychotic-Related DRESS Syndrome: Analysis of Individual Case Safety Reports of the WHO Pharmacovigilance Database.

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear.

Methods: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics.

Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland.

Background: Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term.

Duration of Untreated Psychosis and Outcomes in First-Episode Psychosis: Systematic Review and Meta-analysis of Early Detection and Intervention Strategies.

Background: The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown.

Study Design: PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community.

Examining the Effectiveness of a Digital Media Campaign at Reducing the Duration of Untreated Psychosis in New York State: Results From a Stepped-wedge Randomized Controlled Trial.

Background And Hypothesis: Longer duration of untreated psychosis (DUP) predicts worse outcomes in First Episode Psychosis (FEP). Searching online represents one of the first proactive step toward treatment initiation for many, yet few studies have informed how best to support FEP youth as they engage in early online help-seeking steps to care.

Study Design: Using a stepped-wedge randomized design, this project evaluated the effectiveness of a digital marketing campaign at reducing DUP and raising rates of referrals to FEP services by proactively targeting and engaging prospective patients and their adult allies online.

Racial Disparities Among Clinical High-Risk and First-Episode Psychosis Multisite Research Participants: A Systematic Review.

Objective: The NIH has mandated equal representation of Black, Indigenous, and people of color (BIPOC) individuals in clinical research, but it is unclear whether such inclusion has been achieved in multisite research studies of individuals at clinical high risk for psychosis or with first-episode psychosis (FEP). An assessment of inclusion rates is important for understanding the social determinants of psychosis and psychosis risk that specifically affect BIPOC individuals.

Methods: The authors conducted a systematic review of the literature published between 1993 and 2022 of multisite research studies of clinical high risk for psychosis and FEP in North America to determine ethnoracial inclusion rates.

Replication of a neuroimaging biomarker for striatal dysfunction in psychosis.

To bring biomarkers closer to clinical application, they should be generalizable, reliable, and maintain performance within the constraints of routine clinical conditions. The functional striatal abnormalities (FSA), is among the most advanced neuroimaging biomarkers in schizophrenia, trained to discriminate diagnosis, with post-hoc analyses indicating prognostic properties. Here, we attempt to replicate its diagnostic capabilities measured by the area under the curve (AUC) in receiver operator characteristic curves discriminating individuals with psychosis (n = 101) from healthy controls (n = 51) in the Human Connectome Project for Early Psychosis.