Alarm fatigue threatens patient safety in intensive care units (ICUs), yet no validated Japanese instrument exists. We cross-culturally adapted the Charité Alarm Fatigue Questionnaire (CAFQa) into Japanese following COSMIN guidelines and evaluated it in 129 clinicians (103 nurses, 26 physicians) at five hospitals, with 102 retested. Confirmatory factor analysis supported the two-factor structure (CFI = 0.922; RMSEA = 0.041; SRMR = 0.076), but the inter-factor correlation was near zero (r = 0.05), suggesting that Alarm Stress and Alarm Coping behave as largely independent dimensions. Cronbach's alpha was 0.805 (Stress) and 0.649 (Coping); test-retest ICCs ranged 0.62-0.75. Alarm Stress correlated with job stress (r = 0.256) and insomnia (r = 0.369), whereas Alarm Coping related selectively to relational and environmental factors and to ICU experience. Given the orthogonal subscales, we recommend subscale-level rather than total-score interpretation.

Major depressive disorder is increasingly conceptualized as a condition involving brain network dysfunction, neuroimmune imbalance, sleep-circadian disruption, hypothalamic-pituitary-adrenal (HPA)-axis dysregulation, monoaminergic arousal instability, and impaired synaptic plasticity. In parallel, the glymphatic system has emerged as a plausible integrative mechanism linking these domains, because it is a glia-dependent pathway supporting cerebrospinal fluid-interstitial fluid exchange and metabolic-waste clearance, with activity strongly modulated by deep non-rapid eye movement (NREM) sleep. This narrative review synthesizes evidence that glymphatic-related magnetic resonance imaging (MRI) proxies, particularly diffusion tensor imaging along the perivascular space (DTI-ALPS), are altered in depression, while emphasizing that DTI-ALPS is an indirect marker of perivascular diffusion rather than a direct measure of glymphatic flow. We define four key research gaps: scarcity of treatment-resistant depression (TRD)-specific cohorts, regional and technical heterogeneity across MRI studies, and uncertainty about causal direction relative to sleep disturbance and inflammation. Altered indices appear to relate to fatigue, psychomotor retardation, cognitive impairment, rumination, suicidality, systemic inflammation, oxidative stress, and HPA-axis dysregulation. We integrate opposite-direction findings, including elevated ALPS in drug-naive somatic depression, into a state- and subtype-dependent working model rather than a unidirectional dysfunction framework. Therapeutic implications are organized by target specificity, including sleep-dependent clearance, perivascular exchange, aquaporin-4 (AQP4) polarization, vascular pulsatility, and neuroimmune modulation. We propose falsifiable predictions and negative-control analyses to distinguish a glymphatic-related model from additive effects of insomnia, inflammation, and vascular risk. Overall, the current evidence supports a cautious translational framework for biomarker-informed trials in TRD-relevant phenotypes rather than a validated diagnostic biomarker.

Depression is one of the most common and disabling neuropsychiatric complications of neurodegenerative diseases. In Alzheimer's disease (AD) and Parkinson's disease (PD), depressive syndromes affect more than one-third of patients and are associated with accelerated cognitive decline, reduced quality of life, and increased healthcare utilisation. Despite this burden, current antidepressant treatments show little or no efficacy in these populations, suggesting that depression arising in the context of neurodegeneration may reflect distinct underlying neurobiological mechanisms. Emerging evidence from molecular imaging, neuropathology, and cognitive neuroscience indicates disease-specific disruption of monoaminergic, glutamatergic, inflammatory, and reward-related circuits in AD and PD. These alterations may undermine the mechanisms of action of standard antidepressants and contribute to treatment resistance. Yet patients with cognitive impairment are routinely excluded from antidepressant trials, and few high-quality studies have evaluated novel therapies in neurodegenerative disease. In this narrative review, we synthesise current evidence on the neurobiological mechanisms underpinning depression in AD and PD and critically evaluate emerging pharmacological and neuromodulatory therapies targeting glutamatergic, serotonergic, dopaminergic, immune, and circuit-level dysfunction. Here, we highlight that depression in neurodegenerative disease offers a unique and underutilised model for mechanistically guided antidepressant development. We identify how interventions including glutamate modulators, dopaminergic agents, kappa opioid antagonists, immune-modulating therapies, and next-generation brain stimulation approaches may offer therapeutic promise. By aligning treatment development with disease-specific circuit and molecular pathology, this framework may improve outcomes for this neglected population while advancing precision psychiatry more broadly.

BackgroundSleep problems are common in later life and linked to increased morbidity and mortality. African American and low-income older adults disproportionately experience sleep problems.ObjectiveOur aim was to identify factors perceived to affect sleep and garner feedback on potential components of a behavioral sleep intervention.MethodsWe conducted 21 semi-structured interviews with adults in an underserved urban community aged 50 to 74 (77% African American) reporting persistently poor sleep. We used a rapid qualitative analysis approach to develop themes.ResultsResults revealed multilevel sleep barriers related to both life stage and setting: for example, stress, chronic pain, vigilance due to security concerns and caregiving, and noise. All participants wanted to improve sleep without medications. Intervention components of most interest were contact with a community health worker, a watch to track sleep, and educational resources. The barriers identified here should be addressed in interventions to improve sleep in this population.

BackgroundRimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for both acute and preventive treatment of episodic migraine. Real-world data on its preventive use remain limited, particularly in patients with multiple prior preventive failures. This study evaluated the effectiveness and tolerability of rimegepant in routine clinical practice, focusing on a highly treatment-resistant population.MethodsWe conducted a prospective, multicenter real-world cohort study within the GEMA (GEpants in MigrAine) Project across nine tertiary Headache Units in Spain. Adults initiating rimegepant for migraine prevention were consecutively enrolled and followed for up to 6 months. The primary endpoint was the 3-month change in monthly headache days (MHD). Secondary endpoints included the change in monthly migraine days (MMD), response rates, predictors of response, and tolerability. Baseline characteristics, prior preventive failures, medication overuse, adverse events, and patient-reported outcomes (Headache Impact Test-6 (HIT-6), HADS, and Insomnia Severity Index) were recorded.ResultsIn total, 150 patients completed 3-month follow-up and 64 reached 6 months. The cohort was predominantly female (85.3%), with 70.7% episodic migraine, a median age of 48 years (interquartile range (IQR) = 39-57), and a median of 6 prior preventive failures (IQR = 4-8), reflecting high treatment resistance. At 3 months, median MHD decreased from 12 to 7.5 and MMD from 10 to 6 (p < 0.05), with significant improvement in HIT-6. Overall, 36% and 43% achieved ≥ 50% reduction in MHD and MMD, respectively (≥ 75%: 15% and 20%). Among patients with 6-month data, further reductions were observed (MHD, 6 days; MMD, 5 days), with ≥ 50% response rates increasing to 48% and 58%. Clinical responders showed greater improvements in anxiety and depressive symptoms. Medication overuse, chronic migraine, and prior exposure to anti-CGRP monoclonal antibodies and onabotulinumtoxinA were independent predictors of poorer outcomes, with response declining with increasing prior anti-CGRP exposure, although a relevant proportion still achieved meaningful benefit. Rimegepant was well tolerated, with predominantly mild adverse events (nausea 13%, constipation 8%) and low discontinuation (7% at 3 months), and with nausea being the most frequent cause.ConclusionsRimegepant showed meaningful preventive effectiveness and good tolerability in routine clinical practice, including in highly treatment-resistant patients with prior anti-CGRP monoclonal antibody exposure. The response was influenced by baseline disease burden and prior treatment exposure. These findings suggest that earlier use of rimegepant in the treatment course may be associated with greater clinical benefit.