Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

BACKGROUND: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. METHODS: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. RESULTS: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. CONCLUSIONS: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. Results: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. Conclusions: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Antibiotic prescribing for respiratory tract infection in patients with suspected and proven COVID-19: results from an antibiotic point prevalence survey in Scottish hospitals.

BACKGROUND: Bacterial co-infection is infrequently observed with SARS-CoV-2/COVID-19 infection outside of critical care, however, antibiotics are commonly prescribed. OBJECTIVES: To examine factors associated with antibiotic prescribing for suspected respiratory tract infection (RTI) and evaluate the nature and dynamics of prescribing in hospitalized patients with suspected and proven COVID-19 infection. METHODS: An antibiotic point prevalence survey in hospitalized adult patients was conducted in designated COVID-19 clinical areas (including critical care) in 15 Scottish hospitals. Antibiotics prescribed for RTI and factors associated with prescribing were investigated. RESULTS: Of 820 surveyed patients, 272 (prevalence 33.3%) received antibiotics for suspected RTI on the survey day and 58.8% were SARS-CoV-2 positive. Antibiotics were empirical in 91.9% and amoxicillin (24.6%), doxycycline (20.5%) and co-amoxiclav (15%) were most frequently prescribed. Oral antibiotics were prescribed in 54.5% and duration was recorded in 76.7% on wards for a median of 5 days. IV to oral switch occurred after a median of 2 days. Prescribing for RTI was independently and positively associated with COPD/chronic lung disease, purulent/bloody sputum, abnormal chest X-ray, and CRP ≥ 100 mg/L. Probable and definite hospital-acquired COVID-19 and diabetes were associated with a lower odds of receiving an antibiotic for RTI. CONCLUSIONS: Antibiotic prescribing for suspected RTI was commonly observed and predominantly empirical in suspected or proven COVID-19. Initiatives to reinforce stewardship principles including clinical review, effective use of microbiological diagnostics and better understanding of the role of biomarkers are central to further limit unnecessary antibiotic therapy in COVID-19.

Relational memory in the early stage of psychotic bipolar disorder.

Relational memory is impaired in psychotic disorders. In non-affective psychotic disorders, relational memory deficits are present in the early stage of illness and become more pronounced in the chronic stage. Previous studies have demonstrated cognitive deficits in early-stage psychotic bipolar disorder, but it is unclear whether relational memory is impaired. We examined relational memory using a face-scene binding task in early-stage psychotic bipolar disorder patients (n = 33) and compared their performance with healthy control (n = 40) and early-stage non-affective psychosis participants (n = 40). During training, participants learned to associate faces with background scenes. During testing, participants viewed a scene overlaid by three faces and were asked to recall the matching face. Relational memory was assessed indirectly using eye movements and explicitly using forced-choice recognition. Preferential viewing of the matching face, as captured by overall proportion of viewing and viewing across time, was significantly lower in psychotic bipolar disorder than in the healthy control group. However, preferential viewing of the matching face in psychotic bipolar disorder was significantly better than in non-affective psychosis. These findings provide novel evidence that relational memory in patients with early-stage psychotic bipolar disorder is intermediate between healthy control and early-stage non-affective psychosis subjects.

Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals.

BACKGROUND: Concern regarding bacterial co-infection complicating SARS-CoV-2 has created a challenge for antimicrobial stewardship. Following introduction of national antibiotic recommendations for suspected bacterial respiratory tract infection complicating COVID-19, a point prevalence survey of prescribing was conducted across acute hospitals in Scotland. METHODS: Patients in designated COVID-19 units were included and demographic, clinical and antimicrobial data were collected from 15 hospitals on a single day between 20th and 30th April 2020. Comparisons were made between SARS-CoV-2 positive and negative patients and patients on non-critical care and critical care units. Factors associated with antibiotic prescribing in SARS-CoV-2 positive patients were examined using Univariable and multivariable regression analyses. FINDINGS: There were 820 patients were included, 64.8% were SARS-CoV-2 positive and 14.9% were managed in critical care, and 22.1% of SARS-CoV-2 infections were considered probable or definite nosocomial infections. On the survey day, antibiotic prevalence was 45.0% and 73.9% were prescribed for suspected respiratory tract infection. Amoxicillin, doxycycline and co-amoxiclav accounted for over half of all antibiotics in non-critical care wards and meropenem, piperacillin-tazobactam and co-amoxiclav accounted for approximately half prescribed in critical care. Of all SARS-CoV-2 patients, 38.3% were prescribed antibiotics. In a multivariable logistic regression analysis, COPD/chronic lung disease and CRP ≥ 100 mg/l were associated with higher odds and probable or confirmed nosocomial COVID-19, diabetes and management on an elderly care ward had lower odds of an antibiotic prescription. Systemic antifungals were prescribed in 9.8% of critical care patients and commenced a median of 18 days after critical care admission. INTERPRETATION: A relatively low prevalence of antibiotic prescribing in SARS-CoV-2 hospitalised patients and low proportion of broad spectrum antibiotics in non-critical care settings was observed potentially reflecting national antimicrobial stewardship initiatives. Broad spectrum antibiotic and antifungal prescribing in critical care units was observed indicating the importance of infection prevention and control and stewardship initiatives in this setting. FUNDING: The Scottish Antibiotic Prescribing Group is funded by Scottish Government.

Antimicrobial point prevalence surveys in two Ghanaian hospitals: opportunities for antimicrobial stewardship.

BACKGROUND: Improved knowledge regarding antimicrobial use in Ghana is needed to reduce antimicrobial resistance (AMR). This includes point prevalence studies (PPSs) in hospitals. Objectives were to: (i) provide baseline data in two hospitals [Keta Municipal Hospital (KMH) and Ghana Police Hospital (GPH)] and identify priorities for improvement; (ii) assess the feasibility of conducting PPSs; and (iii) compare results with other studies. METHODS: Standard PPS design using the Global PPS paper forms, subsequently transferred to their template. Training undertaken by the Scottish team. Quality indicators included: rationale for use; stop/review dates; and guideline compliance. RESULTS: Prevalence of antibiotic use was 65.0% in GPH and 82.0% in KMH. Penicillins and other ß-lactam antibiotics were the most frequently prescribed in both hospitals, with third-generation cephalosporins mainly used in GPH. Antibiotic treatment was mainly empirical and commonly administered intravenously, duration was generally short with timely oral switching and infections were mainly community acquired. Encouragingly, there was good documentation of the indications for antibiotic use in both hospitals and 50.0%-66.7% guideline compliance (although for many indications no guideline existed). In addition, almost all prescribed antibiotics had stop dates and there were no missed doses. The duration of use for surgical prophylaxis was generally more than 1 day (69.0% in GPH and 77.0% in KMH). CONCLUSIONS: These two hospitals were the first in Ghana to use the Global PPS system. We found the PPS was feasible, relatively rapid and achieved with limited training. Targets for improvement identified included reduction of broad-spectrum antibiotics and duration of treatment.

Differential patterns of contextual organization of memory in first-episode psychosis.

Contextual information is used to support and organize episodic memory. Prior research has reliably shown memory deficits in psychosis; however, little research has characterized how this population uses contextual information during memory recall. We employed an approach founded in a computational framework of free recall to quantify how individuals with first episode of psychosis (FEP, N = 97) and controls (CON, N = 55) use temporal and semantic context to organize memory recall. Free recall was characterized using the Hopkins Verbal Learning Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall: proportion recalled, temporal clustering, and semantic clustering. Measures of temporal/semantic clustering quantified how individuals use contextual information to organize memory recall. We also assessed to what extent these measures relate to antipsychotic use and differentiated between different types of psychosis. We also explored the relationship between these measures and intelligence. In comparison to CON, FEP had reduced recall and less temporal clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected). Within FEP, antipsychotic use and diagnoses did not differentiate between free recall accuracy or contextual organization of memory. IQ was related to free recall accuracy, but not the use of contextual information during recall in either group (p < 0.05, Bonferroni-corrected). These results show that in addition to deficits in memory recall, FEP differed in how they organize memories compared to CON.