To validate a predictive risk score of early aggressive pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment with continuous infusion (CI) piperacillin/tazobactam or meropenem in a retrospective cohort of critically ill patients having documented Gram-negative infections.

Critically ill adult patients receiving treatment of documented Gram-negative infections with CI piperacillin-tazobactam or meropenem and undergoing first real-time beta-lactam therapeutic drug monitoring (TDM) instance within 72 h from starting standard dosing regimens were retrospectively included. A receiving operating characteristic (ROC) curve analysis was performed by using the proposed predictive score as the test variable and early aggressive PK/PD target non-attainment as the state variable. Area under the curve (AUC) and 95% confidence interval were calculated. The identified cut-off risk values were used for stratifying patients and assessing the impact on clinical/microbiological outcome in each sub-cohort of patients receiving targeted monotherapy.

Overall, 209 and 203 patients receiving CI piperacillin-tazobactam and meropenem were included, respectively. Early aggressive PK/PD target non-attainment was reported in 33 cases (15.8%) receiving piperacillin-tazobactam and in 8 (3.9%) of those treated with meropenem. A score threshold ≥ 2 points for piperacillin-tazobactam (AUC 0.81; 95% CI 0.75-0.86; p < 0.0001) and ≥ 3 points for patients treated with meropenem (AUC 0.96; 95% CI 0.93-0.99; p < 0.0001) were significantly associated with early aggressive PK/PD target non-attainment. Patients achieving the cut-off predictive score showed a significant higher microbiological failure rate in both piperacillin-tazobactam (56.3% vs. 28.6%, p = 0.044) and meropenem sub-cohorts (50.0% vs. 10.4%, p = 0.028).

Our findings suggest that the proposed predictive cut-off risk score may represent a valuable tool for identifying promptly critically ill patients at high risk of early aggressive PK/PD target non-attainment with CI piperacillin-tazobactam or meropenem for whom a more intensified CI dosing regimens should be promptly applied bedside.

Postoperative delirium (POD) is common after head and neck tumor surgery with free flaps, compromising immobilization and flap survival. However, robust tools for early POD severity prediction and systematic studies on onset-time heterogeneity are lacking.

In a retrospective cohort of 65 POD patients, demographic, perioperative, and postoperative data were analyzed. POD was subclassified by severity (CAM-ICU-7 score) and onset time (24-hour threshold). Descriptive, univariate and multivariate analyses identified independent influencing factors, and a prediction model for POD severity was developed and evaluated.

Severity: 39 severe and 26 non-severe, differing in mental state, clinical manifestations, onset time, duration, and olanzapine dose. Preoperative platelet-to-lymphocyte ratio (PLR) and intraoperative tropisetron dosage were independent influencing factors. The nomogram showed strong discrimination (AUC = 0.830), good calibration and clinical benefit. Onset time: 33 acute and 32 delayed, differing in POD duration and olanzapine dose. Preoperative diastolic blood pressure and PLR were independent influencing factors.

POD after head and neck tumor surgery shows marked heterogeneity in severity and onset. Neutrophils and platelets may respectively drive neuroinflammation occurrence and progression, synergizing with blood pressure to regulate POD subtyping. Identified factors enable early multidimensional warning. The prediction model performs well with optimal threshold 0.45-0.55.

African migrants constitute a significant proportion of the Australian population. While migration and resettlement offer opportunities, the associated stressors may adversely affect the mental health and well-being of African migrants. This study explored, for the first time, the prevalence of depression and psychological distress among African migrants in Australia and the relationship between coping mechanisms and mental health outcomes.

A web-based cross-sectional survey of adult African migrants in Australia was conducted between February and May 2022. Participants (N = 167) who did not have a refugee status who resided in Australia for at least 12 months were recruited through community groups. An e-link of the survey created in Qualtrics was posted on online platforms (WhatsApp, LinkedIn, Twitter, and Facebook) and distributed via emails of community members. The Kessler Psychological Distress Scale (K10) and Patient Health Questionnaire (PHQ-9) assessed mental health outcomes and the Brief COPE assessed coping strategies. Descriptive and multivariate regression analyses were used to determine the association between demographic variables, language ability, and mental health outcomes.

Most respondents (45.2%) were between 35 and 44 years of age and were proficient in English. Approximately one in three individuals reported higher levels of either depression or psychological distress, while 30.9% reported higher levels of both mental health outcomes. Age-specific rates revealed higher levels of depression and psychological distress among younger participants (18-24 years, 62.5%) compared to older age groups (55-59 years, 22.2%; p < 0.05, for both). Coping strategies, such as self-blame, self-distraction, and behavioural disengagement, were significant predictors of depression. Similar findings were observed for psychological distress, with self-blame, behavioural disengagement, and religious coping identified as significant predictors. Notably, language ability did not significantly differ between groups with varying levels of depression or distress. However, the distressed group was significantly younger than the non-distressed group (X² (n = 131) = -2.13, p = 0.03), while the higher depression group tended to be younger than the minimal depression group (X² (n = 124) = -2.67, p = 0.08).

These findings highlight the importance of addressing mental health issues and promoting effective coping strategies among African migrants in Australia, particularly targeting young individuals.

It is hypothesised that structural brain abnormalities in individuals with schizophrenia are associated with aggressive behaviour, but this has not been tested directly. We pooled magnetic resonance imaging and clinical data from 2095 patients and 2861 healthy control subjects across 20 sites of the ENIGMA-Schizophrenia Working Group. Using normative modelling, we quantified individual-level deviations from controls (z-scores) for global and regional grey matter volume and white matter microstructural integrity. Ordinal regression models were used to estimate the associations between these deviations and concurrent aggression (odds ratios [ORs] with 99% confidence intervals [CIs]). In mediation analyses, we examined the roles of positive symptoms - delusions, hallucinations and disorganised thinking - impulsivity and illness insight. Aggression was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = 0.003), global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10^-5), dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p = 0.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10^-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10^-4). These associations were robust to adjustment for relevant covariates and partly mediated by positive symptoms and impulsivity. Our findings suggest that the co-occurrence of positive symptoms, impulsivity and aggression in schizophrenia has a neurobiological basis, providing potential targets for therapeutic interventions.

Professional grief is a global challenge in oncology nursing. It refers to the constellation of grief reactions experienced by nurses after the death of patients under their care, and it seriously undermines mental health and job performance. Psychological resilience-a positive psychological attribute-enables individuals to achieve adaptive adjustment and maintain mental well-being. However, systematic evidence on the inter-relationships among psychological resilience, positive coping styles, and professional grief is lacking. This study clarifies how psychological resilience relates to professional grief among oncology nurses and elucidates the mechanisms through which positive coping styles operate. The findings furnish international nurse managers with a low-cost, high-impact target for psychological interventions and expand the global evidence map for prevention and mitigation professional grief. A questionnaire survey was conducted using purposive sampling among 540 oncology nurses in fifteen tertiary-level hospitals in Sichuan Province from November 2024 to February 2025. Instruments included psychological resilience (MeRS), positive coping styles (SCSQ), and professional grief (GSSN). A total of 518 valid questionnaires were returned, with an effective response rate of 95.9%. The results showed that psychological resilience had a significant direct effect on professional grief (β =  - 0.511, 95% CI [- 0.374, - 0.280]), a positive effect on positive coping styles (β = 0.526, 95% CI [0.177, 0.232]), and-via the mediator-remained significantly associated with professional grief (β =  - 0.346, 95% CI [- 0.275, - 0.168]). Positive coping styles, in turn, significantly predicted lower professional grief (β =  - 0.313, 95% CI [- 0.656, - 0.375]). Positive coping styles partially mediated the relationship between psychological resilience and professional grief among oncology nurses, with a mediation effect value of 0.164 and a mediation effect of 32.094% of the total effect. This is the non-Western study to delineate a mechanistic pathway from resilience to reduced grief via positive coping styles. The model is culture-independent and cost-effective, offering global oncology managers a concrete lever-strengthening positive coping-to mitigate nurses' grief and safeguard workforce well-being.

This study aimed to systematically review and meta-analyze the effectiveness of eHealth-based cardiovascular disease (CVD) risk communication and its impact on health-related outcomes. Twenty-three RCTs were included. The eHealth-based CVD risk communication showed significant improvements in controlling systolic blood pressure (P = 0.03), low-density lipoprotein (P = 0.02), physical activity (P = 0.003), smoking cessation (P = 0.004), disease awareness (P = 0.002), and quality of life (P = 0.03). No significant effects were found for other outcomes, including diastolic blood pressure, total cholesterol, and overall risk scores. These findings provide valuable insights into the potential role of eHealth-based risk communication in CVD prevention. In addition, existing risk communication interventions are multicomponent, and future research could standardize intervention components and optimize intervention elements using the Behavior Change Techniques Taxonomy and factorial designs, while developing targeted risk communication strategies for different populations to improve health outcomes.

Electroconvulsive therapy (ECT) is an effective antidepressant treatment. The mechanisms behind the therapeutic effect are not fully understood, and reliable biomarkers for response are needed. Epigenetic modifications, such as DNA methylation (DNAm), can reflect both genetic and environmental impacts; they may shed light on the mechanisms behind treatment effects and they have the potential to inform response prediction. We performed an epigenome-wide association study (EWAS) in peripheral blood from patients before and after ECT in a Norwegian cohort (n = 65). The methylation levels of 12 differentially methylated CpG positions (DMPs) and 18 differentially methylated regions (DMRs) were significantly associated with percent clinical response. In addition, 29 DMPs and 23 DMRs were significantly associated with remission (Montgomery and Åsberg Depression Rating Scale MADRS < 10 post treatment). Two DMRs were also significantly associated with percent response at baseline and four DMRs were significantly associated with remission at baseline (FDR < 0.05). We did not identify any longitudinal (pre-post) changes in DNAm. We further performed the first meta-analysis (n = 99) between ECT cohorts, combining this Norwegian cohort and a German ECT cohort (n = 34). Seven of the DMRs found to be associated with response in the meta-analyses were previously identified in the Norwegian or the German cohort (FDR < 0.05). Methylation risk scores (MS) calculated using DMPs associated with ECT in the Norwegian cohort showed promising association with response to ECT in the German cohort (p = 0.06). Finally, we found increased neutrophil to lymphocyte ratios, calculated from estimated cell proportions, to be associated with remission (p < 0.003) in the Norwegian cohort.

Over the past two decades, foundational work has provided key insights into the cognitive and neural basis of hallucinations. This progress has led to the development of several families of theories, each of which propose that hallucinations arise from distinct cognitive mechanisms. Since these cognitive mechanisms likely map onto separate circuit-level implementations, arbitrating between them is critical to advance our understanding of hallucination pathophysiology and guide the development of novel targeted therapeutics. However, several obstacles have hindered this progress, including the under-specification of theories and inadequate comparative testing. To overcome these challenges, and following best practices in cognitive computational neuroscience, theories should 1) articulate computational and biological details at a level that allows the generation of precise, testable predictions, and 2) be evaluated using experiments designed to emphasize their unique signatures to facilitate falsification. To illustrate this general approach, we demonstrate how theory-driven computational models constrained by well-replicated findings across basic, preclinical, and clinical neuroscience can provide a principled means to prioritize falsifiable mechanistic theories of auditory hallucinations. We then discuss how these models can be used to inform the development of richer behavioral paradigms and analytical approaches that enable direct comparisons between competing theories. Overall, we propose a general strategy for the specification and falsification of candidate mechanisms underlying (auditory) hallucinations - a critical prerequisite for refining hallucination theories and advancing their translational potential.

Obesity is a chronic systemic disease with multifactorial causes that poses a substantial health and economic burden worldwide. In Korea, obesity is a significant public health concern owing to the increasing prevalence of obesity-related comorbidities and mortality. Obesity is defined as excess adiposity that poses health risks. Adiposity can be assessed using direct and indirect methods, among which body mass index (BMI) is the most widely used anthropometric measurement in epidemiological studies and clinical practice. However, limitations of BMI-centric obesity assessments have been noted in previous studies. Simple adiposity measures cannot capture obesity-related medical conditions, daily functional status, or mental health. Therefore, medical associations worldwide have increasingly emphasized the need for comprehensive obesity assessments, including the 2020 Canadian Adult Obesity Clinical Practice Guidelines, American Association of Clinical Endocrinologists/American College of Endocrinology 2023 Guidelines, 2024 European Association for the Study of Obesity diagnostic framework, and 2025 Lancet Commission's Clinical Obesity Diagnostic Criteria. Recent perspectives have emphasized multidimensional approaches to obesity assessment to capture individuals' overall health status. This review aims to evaluate the limitations of BMI-centric obesity diagnosis, summarize emerging recommendations from recent international guidelines, and highlight potential alternative approaches for improving the assessment of obesity and related health outcomes.

To evaluate and synthesize interpretability metrics, including minimal important change (MIC), minimal important difference (MID), and minimal detectable change (MDC), across PROMIS and related systems (Neuro-QoL, TBI-QoL, SCI-QoL) in rehabilitation populations.

Comprehensive searches of electronic databases (MEDLINE, EMBASE, PsycINFO, HaPI, CINAHL, Cochrane Library, Web of Science) and clinical trial registries (ISRCTN Registry, ClinicalTrials.gov) were conducted from inception through March 23, 2024, in consultation with an information specialist.

Eligible studies assessed interpretability metrics in rehabilitation populations using PROMIS, Neuro-QoL, TBI-QoL, or SCI-QoL. Studies of pediatric or non-rehabilitation populations, abstracts, posters, or consensus statements were excluded. A total of 202 studies met inclusion criteria.

Two independent reviewers extracted study characteristics, interpretability metrics, and analytic methods following COnsensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

MIC, MID, and MDC values varied widely across populations and domains. PROMIS mental health domains (e.g., depression, anxiety, fatigue) demonstrated relatively consistent estimates, whereas physical function domains were more variable, particularly in chronic and geriatric groups. PROMIS Computer Adaptive Testing (CAT) measures showed fewer floor and ceiling effects than short forms, indicating enhanced sensitivity to change. Limited data were available for SCI-QoL and TBI-QoL.

Standardizing interpretability metrics and expanding research on SCI-QoL and TBI-QoL are critical to improving the clinical utility of these measures in rehabilitation. Future work should incorporate response-shift considerations and establish population-specific cut-points to support patient-centered care and evidence-based practice.