Background: Frailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality. Materials: Two cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR. Methods: Kaplan–Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0–05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years. Results: Frailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29–0.66)), age (1.05 (1.01–1.09)), weight (0.98 (0.96–1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41–0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33–0.74)), SPPB sit and stand (0.62 (0.45–0.85)), heart failure (0.67 (0.46–0.98)), use of antiplatelets (1.80 (1.19–2.71)), and quetiapine (0.31 (0.12–0.81)). Specific high-risk factors in the pre-frail cohort are Barthel’s score (120 (7.7–1700)), Pfeiffer test (8.4; (2.3–31)), Mini Nutritional Assessment (MNA) (1200 (18–88,000)), constipation (0.025 (0.0027–0.24)), falls (18,000 (150–2,200,000)), deep venous thrombosis (8400 (19–3,700,000)), cerebrovascular disease (0.01 (0.00064–0.16)), diabetes (360 (3.4–39,000)), thyroid disease (0.00099 (0.000012–0.085)), and the use of PPIs (0.062 (0.0072–0.54)), Zolpidem (0.000014 (0.0000000021–0.092)), antidiabetics (0.00015 (0.00000042–0.051)), diuretics (0.0003 (0.000004–0.022)), and opiates (0.000069 (0.00000035–0.013)). Conclusions: Frailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.

This study aims to determine when frailty increases the risks of delirium mortality. Hospital patients falling into the elderly frail or pre-frail category were recruited, some without delirium, some with delirium at admission, and some who developed delirium during admission. We screened for frailty, cognitive status, and co-morbidities whenever possible and extracted drug information and mortality data from electronic health records. Kaplan–Meier estimates of survival probability functions were computed at four times, comparing delirium versus non delirium patients. Differences in survival were assessed by a log-rank test. Independent Cox’s regression was carried out to identify significant hazard risks (HR) at 1 month, 6 months, 1 year, and 2 years. Delirium predicted mortality (log-rank test, p < 0.0001) at all four censoring points. Variables with significant HRs were frailty indicators, comorbidities, polypharmacy, and the use of specific drugs. For the delirium cohort, variables with the most significant 2-year hazard risks (HR(95%CI)) were: male gender (0.43 20 (0.26,0.69)), weight loss (0.45 (0.26,0.74)), sit and stand up test (0.67 (0.49,0.92)), readmission within 30 days of discharge (0.50 (0.30,0.80)), cerebrovascular disease (0.45 (0.27,0.76)), head trauma (0.54 22 (0.29,0.98)), number of prescribed drugs (1.10 (1.03,1.18)), and the use of diuretics (0.57 (0.34,0.96)). These results suggest that polypharmacy and the use of diuretics increase mortality in frail elderly patients with delirium.

Both genetic and environmental factors have been found to play a significant role in psychosis relapse, either independently or through their synergistic interaction. Recently, DNA methylation (DNAm) has been proposed through the calculation of methylation profile scores (MPS). The aim of the present study is to evaluate the association of MPS as a surrogate marker of the biological impact of early stressful life events (including stressful intrauterine conditions and obstetric complications, childhood adversity and toxic habits), with the risk of schizophrenia (SCZ) relapse. 91 participants from a cohort of first-episode schizophrenia (FES) patients with less than five years of evolution were classified as non-relapse (patients who had not experienced a relapse after 3 years of enrollment) or relapse (patients who relapsed during the 3-year follow-up). As inclusion criteria, patients fulfilled Andreasen's criteria of symptomatic remission. Genome-wide DNA methylation (DNAm) was profiled and fourteen MPS reflecting environmental exposure were constructed including both early stressful life events (including stressful intrauterine conditions and delivery issues, childhood adversity) and toxic habits. Increased levels of MPS reflecting gestational diabetes (p = 0.009), hypertensive disorders during pregnancy (p = 0.004), pre-eclampsia (p = 0.049), early preterm birth (p = 0.030), childhood adversity abuse (p = 0.021) and all childhood adversity (p = 0.030) were significantly associated with an increased risk of relapse. Our study suggests that changes in specific methylation patterns may represent one of the biological mechanisms linking early stressful life events to an increased risk of relapse.

Cognitive impairment (CI) in bipolar disorder (BD) significantly impacts overall functioning and quality of life. A better understanding of the neurobiological mechanisms associated with CI is needed. Studies on neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, have revealed promising findings related to retinal thickness alterations using optical coherence tomography (OCT). Similarly, retinal differences between healthy controls and individuals with BD or schizophrenia have been described. This study explores the utility of OCT in discerning retinal changes possibly associated with CI in BD to enhance our understanding of the biological markers of BD and provide additional information to neuropsychological testing. Optical coherence tomography (OCT) was employed to measure retinal thickness in the macular ganglion cell layer (GCL), inner plexiform layer (IPL), retinal nerve fiber layer (RNFL), and peripapillary RNFL (pRNFL) in 50 individuals with bipolar disorder (BD). Associations with cognitive impairments were analyzed using cross-validated Random Forest models. The analysis revealed significant associations between retinal thinning in various segments of the macular GCL, IPL, and RNFL and cognitive impairment (CI) in BD, with particular relevance to executive function deficits (AUC > 0.8). Thinning of the GCL, IPL, and RNFL was significantly associated with worse cognitive performance in individuals with BD. Similar patterns have been observed in schizophrenia, highlighting an innovative and promising field for research and clinical application.

Background: Cognitive impairment is central to psychosis and strongly linked to functional outcomes. The Brief Assessment of Cognition (BAC) app is a tablet-based, automated tool for assessing key cognitive domains but has not been validated in Spanish-speaking populations or across illness stages. Methods: A total of 402 participants (117 with first-episode psychosis [FEP], 125 with schizophrenia, and 160 controls) completed the BAC app along with clinical and functional assessments. We evaluated internal consistency, group differences, convergent and discriminant validity, and the effects of sex, age, and education. Normative percentiles were derived from controls. Results: The BAC app showed good internal consistency across groups (α = 0.76–0.87) and effectively differentiated individuals with psychosis from controls (area under the curve [AUC] = 0.862), with performance declining from controls to FEP to schizophrenia. Discrimination between FEP and schizophrenia was limited (AUC = 0.649). BAC App correlated positively with estimated intelligence quotient and functional capacity, and negatively with symptom severity, particularly in FEP. Performance varied by age, sex, and education, supporting the need for stratified normative data. Conclusions: The BAC app showed strong reliability and validity for cognitive assessment in Spanish-speaking individuals with psychosis. Its brevity, automated scoring, and normative data support its clinical and research applications for cognitive screening, monitoring, and treatment evaluation.