Analysis of Concomitant Medications Prescribed with Antipsychotics to Patients with Dementia.

INTRODUCTION: Antipsychotics are still commonly prescribed to patients with dementia, despite the many issues that have been identified. This study aimed to quantify antipsychotic prescription in patients with dementia and the types of concomitant medications prescribed with antipsychotics. METHODS: A total of 1,512 outpatients with dementia who visited our department between April 1, 2013 and March 31, 2021, were included in this study. Demographic data, dementia subtypes, and regular medication use at the time of the first outpatient visit were investigated. The association between antipsychotic prescriptions and referral sources, dementia subtypes, antidementia drug use, polypharmacy, and prescription of potentially inappropriate medications (PIMs) was evaluated. RESULTS: The antipsychotic prescription rate for patients with dementia was 11.5%. In a comparison of dementia subtypes, the antipsychotic prescription rate was significantly higher for patients with dementia with Lewy bodies (DLB) than for those with all other dementia subtypes. In terms of concomitant medications, patients taking antidementia drugs, polypharmacy, and PIMs were more likely to receive antipsychotic prescriptions than those who were not taking these medications. Multivariate logistic regression analysis showed that referrals from psychiatric institutions, DLB, N-methyl-d-aspartate (NMDA) receptor antagonists, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions. CONCLUSIONS: Referrals from psychiatric institutions, DLB, NMDA receptor antagonist, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions for patients with dementia. To optimise prescription of antipsychotics, it is necessary to improve cooperation between local and specialised medical institutions for accurate diagnosis, evaluate the effects of concomitant medication administration, and solve the prescribing cascade.

Influence of Psychotropic Pro Re Nata Drug Use on Outcomes in Hospitalized Patients with Schizophrenia.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients' outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10-4) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10-4) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10-3). Conclusion: Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project.

BACKGROUND: Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. METHODS: A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. RESULTS: Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). CONCLUSIONS: In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.

A retrospective study on the diagnosis and treatment of dementia in patients referred to the Sagamihara Municipal Medical Center for Dementia for consultation.

AIM: In Japan, the Orange Plan was formulated in 2013 to promote community-based integrated care systems, and in 2015, it was revised as the New Orange Plan. Since the introduction of these programmes, adequate research has not been carried out on how these measures affect regional dementia care. The aim of this study was to investigate the state of community-based dementia treatment through a survey of medical consultation pathways, including dementia diagnosis, at the Sagamihara Municipal Medical Center for Dementia. METHODS: The participants included 1480 patients (585 men, 895 women) who presented for consultation at the Sagamihara Municipal Medical Center for Dementia for a differential diagnosis or treatment of dementia. The relationship between the path leading to medical consultation before pharmacotherapy and post-consultation diagnosis was investigated. RESULTS: Significantly more participants who presented for consultation without a referral were not diagnosed with dementia than diagnosed. Furthermore, among participants referred from a non-psychiatric clinic, significantly more patients were diagnosed with dementia than not. A significant difference was observed in a comparison of facility types and the use or non-use of anti-dementia drugs. Notably, the rate of anti-dementia drug prescriptions was significantly higher in psychiatric hospitals and non-psychiatric clinics. Furthermore, it is possible that approximately 30% of anti-dementia drugs prescribed at each facility were not covered by insurance. CONCLUSION: Community-based integrated care systems aim to promote collaboration within each region aimed. However, appropriate pharmacotherapy methods for dementia patients have not been adequately communicated to non-specialist physicians and local residents. For this reason, human resource solutions are needed to help medical staff deepen their understanding of dementia so that they can better provide dementia support to patients.

Improvement of psychiatrists' clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project: A nationwide dissemination, education, and evaluation study.

AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

Associations between readmission and patient-reported measures in acute psychiatric inpatients: a study protocol for a multicenter prospective longitudinal study (the ePOP-J study).

BACKGROUND: Several previous observational studies have reported the risk factors associated with readmission in people with mental illness. While patient-reported experiences and outcomes have become increasingly important in healthcare, only a few studies have examined these parameters in terms of their direct association with readmission in an acute psychiatric setting. This project will investigate multiple factors associated with readmission and community living in acute psychiatric patients in Japan. This study will primarily investigate whether patient-reported experiences at discharge, particularly quality of life (QoL), are associated with future readmission and whether readmission after the index hospitalization is associated with changes in patient-reported outcomes during the study period. Here, we describe the rationale and methods of this study. METHODS: This multicenter prospective cohort study is being conducted in 21 participating Japanese hospitals, with a target sample of approximately 600 participants admitted to the acute psychiatric ward. The study has four planned assessment points: time of index admission (T1), time of discharge (from the index admission) (T2), 6 months after discharge from the index admission (T3), and 12 months after discharge from the index admission (T4). Participants will complete self-reported measures including a QoL scale, a subjective disability scale, and an empowerment- and self-agency-related scale at each assessment point; additionally, service satisfaction, subjective view of need for services, and subjective relationships with family members will be assessed at T2 and T3. We will assess the participants' hospitalization during the study period and evaluate several potential individual- and service-level factors associated with readmission and patient-reported experiences and outcomes. Multivariate analyses will be conducted to identify potential associations between readmission and patient-reported experiences and outcomes. DISCUSSION: The present study may produce evidence on how patient-reported experiences at discharge influence readmission and on the influence of readmission on the course of patient-reported outcomes from admission to community living after discharge. The study may contribute to improving care for both patients' subjective views of their own health conditions and their community lives in an acute psychiatric setting.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) UMIN000034220. Registered on September 20, 2018.

Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice.

Magnesium (Mg2+) is an essential mineral for maintaining biological functions. One major action of Mg2+ in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg2+ has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg2+ deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.

Web-Based Training Program Using Cognitive Behavioral Therapy to Enhance Cognitive Flexibility and Alleviate Psychological Distress Among Schoolteachers: Pilot Randomized Controlled Trial.

BACKGROUND: Schoolteachers are known to be faced with various stresses in their work. A simple, less onerous, and effective intervention technique that can enhance the stress management skills, particularly, cognitive flexibility, of schoolteachers is needed. OBJECTIVE: This study aimed to determine whether stress management training using a Web-based cognitive behavioral therapy (CBT) program is effective for enhancing the cognitive flexibility of schoolteachers and alleviating their subjective distress. METHODS: This study was conducted in a random controlled design covering public elementary schoolteachers. Teachers allocated to the intervention group received 120 min of group education and completed homework using a Web-based CBT program that lasted for 3 months. The items of outcome evaluation were cognitive flexibility and subjective distress, and the efficacy of intervention was evaluated at 3 months after intervention. RESULTS: A total of 240 participants were randomly allocated to the intervention group (120 individuals) and the control group (120 individuals). On the basis of the principle of intention to treat, the intervention group and the control group were compared regarding the amount of change from before intervention to after intervention, using a general linear model. Scores of cognitive flexibility and subjective distress were significantly more improved in the intervention group than in the control group. CONCLUSIONS: The results of this study suggest that simple stress management training using a Web-based CBT program in elementary schoolteachers enhances cognitive flexibility and alleviates subjective distress.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

[Evaluation of Efficacy and Adverse Effects of Symptomatic Drugs for Alzheimer Disease].

The symptomatic drugs used for the treatment of Alzheimer disease (AD) are considered to exert their effect by suppressing the progression of dementia symptoms. Although clinical trials conducted on the drugs in Japan have revealed statistically significant differences in assessments of change in cognitive function, three of the four drugs have not shown any statis- tically significant differences in the clinician's global impression. There are many overseas reports indicating the efficacy of these drugs, whereas many other reports also indicate that the assessment procedures themselves are difficult and have many limitations. In order to determine the efficacy of the drugs in clinical practice, physicians need to determine whether the progression of dementia symptoms is inhibited. However, AD symptoms vary and are affected by the patient's living environment, personal relationships, and other factors. Although there are certain trends in the time of symptom onset according to disease stages, the symptoms progress by the year and greatly vary among patients. Comparison of progression rates to the average rate is a primary requirement for measurement of the drugs' inhibitory effects on progression. However, because progression rates greatly vary among patients, it is difficult to determine the average rate. In principle, drug therapy should be discontinued if it is not effective. However, because it is difficult to determine whether the drugs are effective, they are likely to be unnecessarily prescribed even when there is a lack of efficacy. The typical adverse effects of cholinesterase inhibitors (ChEIs) include gastrointestinal, neuropsychiatric, extrapyramidal, and cardiovascular symptoms. Transdermal patch formulations of ChEIs may cause pruritus. N-methyl-D-aspartic acid receptor antagonists may also cause various adverse effects. Patients with AD often have impaired ability to recognize psychosomatic changes and to inform people around them of the changes. Thus, detection of adverse effects is likely to be delayed. If the somatic symptoms caused by adverse effects appear as a lack of animation or irritation, the changes due to adverse effects will be likely misunderstood as symptoms caused by progression of AD, behavioral and psychological symptoms. Since the four symptomatic drugs became available, there have been more opportunities to discuss how the use of the drugs can be differentiated. However, the need for using these drugs should be reevaluated before differentiation of their use.

[Frequent psychiatric symptoms in the elderly patients].

In Japan, the elderly patients generally account for high percentages of both inpatients and outpatients. As aging of the population accelerates, it will become increasingly important to properly detect, assess and intervene for psychiatric symptoms of the elderly patients to establish differential diagnoses. Thus, we must assess all existing psychiatric symptoms by keeping in mind the brain/physical conditions and social circumstances of the elderly patients and considering not just their complaints but also objective information from other organizations/services. In doing so, particular emphasis should be placed on assessing consciousness. Decreased alertness should not be dismissed as "old age". Medical professionals and caregivers must carefully assess psychiatric symptoms in the elderly patients while respecting their self-esteem.

[Integrated care in community psychiatric medicine].

A common factor underlying the current issues in psychiatric medicine is the lack of visualization of the process of medical practice. An approach to visualization of this process facilitates solving the problems faced in this field. Psychiatric care often comes into effect based on the cooperation of a number of institutions and professions, rather than being completed within a single institution. To visualize the process of psychiatric care, it is important to establish face-to-face relationships between patients and psychiatrists, introduce the care system in which two doctors share the responsibility of managing a single patient, and formulate an integrated care pathway in the community. Although many consider the clinical pathway concept to be unsuitable for psychiatric practice, it is possible to introduce a community cooperation care pathway into psychiatric practice if consideration is first given to several significant issues. Community cooperation activities in the field of psychiatric care including the integrated care pathway help to harmonize the efforts of supporters, patients, and families, and increase the overall sense of security. It is also expected that such activities will allow us to obtain useful indices for assessing the quality of care.

Subjective experiences of family caregivers of patients with dementia as predictive factors of quality of life.

BACKGROUND: The aim of the present study was to investigate predictive factors of quality of life (QOL) in home caregivers of patients with dementia. METHODS: A total of 118 home caregivers (48 male, 70 female) were asked to complete the World Health Organization (WHO) Quality of Life 26 (WHO/QOL-26) questionnaire, the Pines Burnout Measure (BM), and the Beck Depression Inventory, second edition (BDI-II). Patient demographics and clinical data regarding cognitive impairment, neuropsychiatric symptoms, and dementia severity were obtained from medical records. RESULTS: Spearman rank correlation coefficients revealed that caregiver QOL was significantly correlated with patients' neuropsychiatric symptoms (r=-0.19; P < 0.05), as well as depressive symptoms (r=-0.59, P < 0.01) and burnout (r=-0.59, P < 0.01) in caregivers. Stepwise multiple regression analysis revealed that depressive symptoms in caregivers was the strongest predictor for caregiver QOL (R(2) = 0.37, P < 0.001) and that caregiver QOL was best predicted by the combination of depressive symptoms, burnout, and the cognitive impairment of patients (R(2) = 0.46, P < 0.05). CONCLUSION: The results of the present study demonstrate that subjective experiences of caregivers are more strongly correlated with caregiver QOL than patient-related variables and are thus powerful determinants of caregiver QOL. These findings suggest that caregiver intervention, which aims to increase QOL, may benefit from the incorporation of strategies to reduce depressive symptoms and burnout.

Coronary artery tree and myocardial perfusion in patients with tako-tsubo cardiomyopathy: Evaluation with coronary digital subtraction angiography.

Tako-tsubo cardiomyopathy is characterized by transient left ventricular contractile dysfunction. The precise etiology of tako-tsubo cardiomyopathy remains to be elucidated. We performed coronary angiography in two patients with tako-tsubo cardiomyopathy and evaluated the coronary microcirculation by digital subtraction angiography (DSA). In the acute phase of tako-tsubo cardiomyopathy, coronary DSA demonstrated severely reduced perfusion in the apex. Follow-up DSA showed the restoration of normal myocardial perfusion in the apex. Coronary DSA can simultaneously depict the coronary vessels and myocardial perfusion abnormalities. Furthermore, DSA can also show the relationship between the perfusion territory of the coronary arteries and the region of impaired myocardial perfusion. This technique might support the central role of microcirculation disturbance in tako-tsubo cardiomyopathy.

[Is "functional somatic syndrome" clinically useful?].

The functional somatic syndrome is applied to several syndromes characterized by medically unexplained physical symptoms, such as irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, etc. Both physical and psychiatric treatments are usually necessary for these syndromes and the term functional somatic syndrome was advocated to inform clinicians in America of this fact. However, We believe this term will not be useful in Japan, because most Japanese clinicians are already aware of this fact and treatment is different in each syndrome included in FSS.

Poor performance in Clock-Drawing Test associated with visual memory deficit and reduced bilateral hippocampal and left temporoparietal regional blood flows in Alzheimer's disease patients.

AIM: To investigate the associations of Clock-Drawing Test (CDT) score with neuropsychological test scores and regional cerebral blood flow. METHOD: Twenty-five patients (normal aging, n = 2; mild cognitive impairment, n = 7; Alzheimer's disease [AD], n = 16) participated in this study. Their average age was 74.8 years. RESULTS: CDT score correlated well with the neuropsychological test scores of Mini-Mental State Examination, Clinical Dementia Rating, immediate visual memory, delayed visual memory, and IQ evaluated by Koh's block design. CDT score also had a statistically significant correlation with the regional blood flow in the left hippocampal region as evaluated on 3-D stereotaxic region-of-interest template analysisapplied to single-photon emission computed tomography images. Using a cut-off point of 8/9 in the CDT, the high-CDT group had significantly higher delayed visual memory and IQ scores than the low-CDT group. Moreover, the high-CDT group had significantly higher regional blood flows in the left parietal, left angular and bilateral hippocampal regions than the low-CDT group. CONCLUSION: CDT score correlates well with regional cerebral blood flow that is decreased in the early stage of AD.

[Bone fusion algorithm: a new tool to support decision making].

Three dimensional angio (3D-Angio) is indispensable in neuroradiology, especially for examinations and interventions of cerebral-aneurysms. 3D-Angio has two modes, 3D-DSA and 3D-DA. The former mode is used to determine vessel structures in detail, and the latter is good at simultaneously determining relationships between vascular and osseous structures. However, it is sometimes difficult to determine these relationships with 3D-Angio if they are close together. The relationship between the skull base and adjacent aneurysm is an essential factor in determining treatment strategy. In order to make this determination, we have developed the Bone Fusion function, which reconstructs vessel and osseous structures separately from rotational DSA data and its mask sequence data, respectively, and two independent 3D data sets are fused in one 3D representation. There are three display modes: fusion, vessel only, and bone only, and those structures are clearly identified by different colors on the fusion images. The Bone Fusion function was applied to hundreds of clinical cases in which 3D-DSA and 3D-DA were used. The Bone Fusion provided important information to determine treatment strategy, although those factors were sometimes lost with 3D-DSA and 3D-DA when the studied vasculatures were adjacent to bone. It was especially useful to apply the Bone Fusion function to aneurysms or tumors adjacent to the skull base.

Three-dimensional fusion digital subtraction angiography: new reconstruction algorithm for simultaneous three-dimensional rendering of osseous and vascular information obtained during rotational angiography.

This report describes three-dimensional (3D) fusion digital subtraction angiography (FDSA), a new algorithm for rotational angiography that combines reconstructions of the blood vessels and the osseous frame in a single 3D representation. 3D-FDSA is based on separate reconstructions of the mask and contrast sequences of the rotational acquisition. The two independent 3D data sets (3D-bone and 3D-digital subtraction angiography [DSA]) are fused in a single 3D representation. The algorithm uses a modification of the Feldkamp method that compensates for signal intensity inhomogeneity inherent to the reconstruction of nonsubtracted rotational acquisitions. By separately reconstructing the osseous and vascular information obtained from the rotational angiogram, 3D-FDSA provides optimal angiographic resolution and precise topographic analysis even when the studied vascular tree is in the immediate vicinity of bone.