Incremental medical cost of delirium in elderly patients with cognitive impairment: analysis of a nationwide administrative database in Japan.

OBJECTIVES: Delirium is a neuropsychiatric disorder that commonly occurs in elderly patients with cognitive impairment. The economic burden of delirium in Japan has not been well characterised. In this study, we assessed incremental medical costs of delirium in hospitalised elderly Japanese patients with cognitive impairment. DESIGN: Retrospective, cross-sectional, observational study. SETTING: Administrative data collected from acute care hospitals in Japan between April 2012 and September 2020. PARTICIPANTS: Hospitalised patients ≥65 years old with cognitive impairment were categorised into groups-with and without delirium. Delirium was identified using a delirium identification algorithm based on the International Classification of Diseases 10th Revision codes or antipsychotic prescriptions. OUTCOME MEASURES: Total medical costs during hospitalisation were compared between the groups using a generalised linear model. RESULTS: The study identified 297 600 hospitalised patients ≥65 years of age with cognitive impairment: 39 836 had delirium and 257 764 did not. Patient characteristics such as age, sex, inpatient department and comorbidities were similar between groups. Mean (SD) unadjusted total medical cost during hospitalisation was 979 907.7 (871 366.4) yen for patients with delirium and 816 137.0 (794 745.9) yen for patients without delirium. Adjusted total medical cost was significantly greater for patients with delirium compared with those without delirium (cost ratio=1.09, 95% CI: 1.09 to 1.10; p<0.001). Subgroup analyses revealed significantly higher total medical costs for patients with delirium compared with those without delirium in most subgroups except patients with hemiplegia or paraplegia. CONCLUSIONS: Medical costs during hospitalisation were significantly higher for patients with delirium compared with those without delirium in elderly Japanese patients with cognitive impairment, regardless of patient subgroups such as age, sex, intensive care unit admission and most comorbidities. These findings suggest that delirium prevention strategies are critical to reducing the economic burden as well as psychological/physiological burden in cognitively impaired elderly patients in Japan.

Demographic and clinical characteristics of patients with delirium: analysis of a nationwide Japanese medical database.

OBJECTIVES: Delirium commonly occurs during hospitalisation and is associated with increased mortality, especially in elderly patients. This study aimed to determine the demographic and clinical characteristics of patients with delirium in the Japanese real-world clinical setting using a nationwide database comprising claims and discharge abstract data. DESIGN: This was an observational, cross-sectional, retrospective study in hospitalised patients with an incident delirium identified by a diagnosis based on International Classification of Diseases, 10th Revision codes or initiating antipsychotics recommended for delirium treatment in Japan during their hospitalisation. SETTING: Patients from the Medical Data Vision database including more than 400 acute care hospitals in Japan were evaluated from admission to discharge. PARTICIPANTS: Of the 32 910 227 patients who were included in the database between April 2012 and September 2020, a total of 145 219 patients met the criteria for delirium. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographic and baseline characteristics, comorbidities, clinical profiles and pharmacological treatments were evaluated in patients with delirium. RESULTS: The mean (SD) patient age was 76.5 (13.8) years. More than half of the patients (n=82 159; 56.6%) were male. The most frequent comorbidities were circulatory system diseases, observed in 81 954 (56.4%) patients. Potentially inappropriate medications (PIMs) with risk of delirium including benzodiazepines and opioids were prescribed to 76 798 (52.9%) patients. Approximately three-fourths of these patients (56 949; 74.2%) were prescribed ≥4 PIMs. The most prescribed treatment for delirium was injectable haloperidol (n=82 490; 56.8%). Mean (SD) length of hospitalisation was 16.0 (12.1) days. CONCLUSIONS: The study results provide comprehensive details of the clinical characteristics of patients with delirium and treatment patterns with antipsychotics in the Japanese acute care setting. In this patient population, the prescription rate of injectable haloperidol and PIMs was high, suggesting the need for improved understanding among healthcare providers about the appropriate management of delirium, which may benefit patients.

Modulation of tactile feedback for the execution of dexterous movement.

Although dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive. Yet how somatosensory feedback from the hands is regulated and whether this modulation influences movement remain unclear. We found that mouse tactile afferents recruit neurons in the brainstem cuneate nucleus, whose activity is modulated by distinct classes of local inhibitory neurons. Manipulation of these inhibitory circuits suppresses or enhances the transmission of tactile information, which affects manual behaviors. Top-down cortical pathways innervate cuneate in a complementary pattern, with somatosensory cortical neurons targeting the core tactile region of cuneate and a large rostral cortical population driving feed-forward inhibition of tactile transmission through an inhibitory shell. These findings identify a circuit basis for tactile feedback modulation that enables the effective execution of dexterous movement.

An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway.

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

Kinematic analysis of bimanual movements during food handling by head-fixed rats.

Bimanual coordination, in which both hands work together to achieve a goal, is crucial for the basic needs of life, such as gathering and feeding. Such coordinated motor skill is highly developed in primates, where it has been most extensively studied. Rodents also exhibit remarkable dexterity and coordination of forelimbs during food handling and consumption. However, rodents have been less commonly used in the study of bimanual coordination because of limited quantitative measuring techniques. In this article we describe a high-resolution tracking system that enables kinematic analysis of rat forelimb movement. The system is used to quantify forelimb movements bilaterally in head-fixed rats during food handling and consumption. Forelimb movements occurring naturally during feeding were encoded as continuous three-dimensional trajectories. The trajectories were then automatically segmented and analyzed, using a novel algorithm, according to the laterality of movement speed or the asymmetry of movement direction across the forelimbs. Bilateral forelimb movements were frequently observed during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed, with symmetric bilateral movements quantitatively more common. The proposed method overcomes a limitation in the precise quantification of bimanual coordination in rodents. This enables the use of powerful rodent-based research tools such as optogenetics and chemogenetics in the further investigation of neural mechanisms of bimanual coordination. NEW & NOTEWORTHY We describe a new method for quantifying and classifying three-dimensional, bilateral forelimb trajectories in head-fixed rats. The method overcomes limits on quantifying bimanual coordination in rats. When applied to kinematic analysis of food handling behavior, continuous forelimb trajectories were automatically segmented and classified. Bilateral forelimb movements were observed more frequently than unilateral movements during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed. However, symmetric bilateral forelimb movements were more common.

The NR2B antagonist, ifenprodil, corrects the l-DOPA-induced deficit of bilateral movement and reduces c-Fos expression in the subthalamic nucleus of hemiparkinsonian rats.

The use of NR2B antagonists in Parkinsonism is still controversial. To examine their anti-parkinsonian effects, the NR2B antagonist, ifenprodil, and L-DOPA were administered together and separately in hemiparkinsonian rats (hemi-PD) that were subjected to a cylinder test. Recovery from hypoactivity was achieved by single administration of 3-7 mg/kg of L-DOPA; however, improvement in the deficit of bilateral forelimb use was not observed. When administered alone, ifenprodil had no anti-parkinsonian effects; however, combined administration of ifenprodil and 7 mg/kg of L-DOPA significantly reversed the deficit of bilateral forelimb use without adversely affecting the L-DOPA-induced improvement in motor activity. Next, in order to identify the brain area influenced by L-DOPA and ifenprodil, quantitative analysis of L-DOPA-induced c-Fos immunoreactivity was performed in various brain areas of hemi-PD following administration of L-dopa with and without ifenprodil. Among brain areas with robust c-Fos expression within the motor loop circuit in dopamine-depleted hemispheres, co-administered ifenprodil markedly attenuated L-DOPA-induced c-Fos expression in only the subthalamic nucleus (STN), suggesting that the STN is the primary target for the anti-parkinsonian action of NR2B antagonists.