Prevalence, clinical features, and risk factors of delusions in patients with delirium.

OBJECTIVES: Delirium may be divided into multiple subtypes with different pathological factors. This study aimed to focus on the delirium subtype in which delusions are conspicuous and explore its prevalence, clinical characteristics, and risk factors. METHODS: The subjects were 601 delirium cases referred to the department of psychiatry over 5 years at a general hospital. The Delirium Rating Scale-Revised-98 was used to assess the delusions in patients with delirium, and the features of delusions (delusional form, object, and content) were examined. Multiple regression analysis was applied to determine whether individual factors were associated with the delusions. RESULTS: A total of 78 patients with delirium experienced delusions (13.0%). Most were classified as delusion of reference, such as persecution or poisoning, and 84.3% of patients believed that the persecutors were medical staff members. Older age (p < 0.001), female gender (p < 0.001), and living alone (p < 0.001) were significantly associated with delusions in patients with delirium. CONCLUSIONS: The content of delusions was rooted in the distress caused by the patients' medical situation, and the features and risk factors of the delusions suggested a formal similarity with late paraphrenia and "lack-of-contact paranoia." Psychological interventions that consider the isolation, anxiety, and fear behind delusions may be necessary in the care and treatment of these patients.

Risk factors for inducing violence in patients with delirium.

BACKGROUND: Violence in patients with delirium may occur suddenly and unpredictably in a fluctuating state of consciousness. Although various factors are involved, appropriate assessment and early response to factors related to violence in delirium are expected to prevent dangerous and distressing acts of violence against patients, their families and medical staff, and minimize the use of physical restraint and excessive drug sedation. METHODS: Subjects were 601 delirium cases referred to the department of psychiatry over the course of 5 years at a general hospital. The demographic, clinical, and pharmacological variables of patients with violence (n = 189) were compared with those of patients without violence (n = 412). Logistic regression analysis was applied to determine whether any specific individual factors were associated with violence. RESULTS: Current smoker status (p < .0005), older age (p < .0005), male gender (p = .004), and use of intensive care units (p = .043) were identified as factors associated with violence in patients with delirium. CONCLUSIONS: Screening tools for violence in patients with delirium and adequate management may assist in better outcomes for patients and medical staff. Further research should evaluate the usefulness of nicotine replacement treatment for the prevention of violence during nicotine withdrawal, including whether it is safe for elderly inpatients with a high incidence of delirium in clinical practice.

Factors affecting hallucinations in patients with delirium.

Delirium develops through a multifactorial process and include multiple subtypes with different pathological factors. To refine the treatment and care for delirium, a more detailed examination of these subtypes is needed. Therefore, this study aimed to explore the factors affecting delirium in cases in which hallucinations are conspicuous. In total, 602 delirium cases referred to the psychiatry department at a general hospital between May 2015 and August 2020 were enrolled. The Delirium Rating Scale-revised-98 was used to assess perceptual disturbances and hallucinations in patients with delirium. Multiple regression analysis was applied to determine whether individual factors were associated with the hallucinations. A total of 156 patients with delirium (25.9%) experienced hallucinations, with visual hallucinations being the most common subtype. Alcohol drinking (p < 0.0005), benzodiazepine withdrawal (p = 0.004), and the use of angiotensin II receptor blockers (p = 0.007) or dopamine receptor agonists (p = 0.014) were found to be significantly associated with hallucinations in patients with delirium. The four factors detected in this study could all be reversible contributing factors derived from the use of or withdrawal from exogenous substances.

Significant decrease in delirium referrals after changing hypnotic from benzodiazepine to suvorexant.

BACKGROUND: The use of benzodiazepines (BZDs) causes delirium, especially in elderly people. For this reason, suvorexant has been recommended as the first-line hypnotic in elderly patients. The aim of this study was to determine whether the first-line use of suvorexant, instead of BZDs, decreases referrals for delirium in elderly patients. METHODS: Since May 2016 at Nagoya Ekisaikai Hospital, suvorexant has been recommended as the first-line hypnotic instead of BZDs. In May 2017, suvorexant was adopted as the first-line hypnotic. The number of delirium cases referred to psychiatry was compared among three consecutive periods: period A (May 2015-April 2016), during which BZDs were mainly used for insomnia; period B (May 2016-April 2017), during which the use of suvorexant was recommended instead of BZDs; and period C (May 2017-April 2018), during which suvorexant was principally adopted as the first-line hypnotic for insomnia. Potential confounding factors that may affect the development of delirium were also examined during the three periods. RESULTS: The number of delirium referral cases in elderly patients in each period decreased, from 133 in period A to 86 in period B and 53 in period C. The rate of delirium referral cases decreased significantly every year (P = 9.02 × 10-10 ). Almost no significant confounding factors other than hypnotics were detected during the three periods. CONCLUSION: The referrals for delirium in elderly patients decreased significantly after the hypnotic was changed from BZDs to suvorexant.

Factors associated with the severity of delirium.

BACKGROUND: Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors. METHODS: A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale-revised-98 (DRS-R-98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium. RESULTS: Intensive care unit admission (p = 0.003), use of benzodiazepines (p = 0.01), dementia (p = 0.02), and older age (p = 0.045) were all positively associated the severity of delirium, while use of ß-blockers (p = 0.001) was negatively associated with the severity of delirium. CONCLUSIONS: Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.

Development of Acute Pericarditis Associated with New-onset Rheumatoid Arthritis in a Diabetic Patient with Renal Impairment: The Elusive Nature of Uremia.

Uremic patients may have a variety of organ involvement, however, the precise causality may be impossible to determine in some cases because the symptoms of uremia are also associated with other diseases. With an emphasis on the elusive nature of uremia, we herein describe a 53-year-old man with preexisting renal impairment who developed acute pericarditis with deterioration of his renal function. Hemodialysis was immediately initiated on the presumption of uremia, however, articular symptoms emerged approximately a month later and led to a final diagnosis of rheumatoid arthritis, followed by successful withdrawal of hemodialysis.

High-sensitivity troponin T as a marker to predict cardiotoxicity in breast cancer patients with adjuvant trastuzumab therapy.

The humanized monoclonal antibody trastuzumab has been in routine use for chemotherapy for human epidermal growth factor receptor II (HER2)-positive breast cancer. A major adverse effect of trastuzumab is cardiotoxicity. Well-established biomarkers or echocardiographic parameters to predict trastuzumab-induced cardiotoxicity have not yet been determined. We attempted to identify useful biomarkers and/or echocardiographic parameters to predict trastuzumab-induced cardiotoxicity. We prospectively investigated the cases of 19 women who received chemotherapy including anthracyclines and trastuzumab for HER2-positive breast cancer. We measured cardiac biomarkers and echocardiographic parameters before their chemotherapy and every 3 months up to 15 months until the end of the adjuvant trastuzumab therapy. We divided the patients into two groups: group R was the nine patients who showed a reduction of left ventricular ejection fraction (LVEF) ≥5%, and group N was the 10 patients who showed a reduction of LVEF <5%. The high-sensitivity troponin T (hs-TnT) level at 6 months was significantly higher in group R than in group N (11.0 ± 7.8 pg/mL vs. 4.0 ± 1.4 pg/mL, p < 0.01). The hs-TnT level with a cutoff value of 5.5 pg/mL at 6 months had 78% sensitivity and 80% specificity for predicting a reduction of LVEF at 15 months. In our evaluation of echocardiographic parameters at baseline, the diastolic function was more impaired in group R than in group N. The hs-TnT and echocardiographic parameters of diastolic function could be useful to predict trastuzumab-induced cardiotoxicity.

Rapid selection of XO embryonic stem cells using Y chromosome-linked GFP transgenic mice.

We developed a transgenic mouse line with Y chromosome-linked green fluorescent protein expressing transgenes (Y-GFP) by the conventional microinjection into the pronucleus of C57BL/6J fertilized oocytes. Embryonic stem (ES) cells derived from Y-GFP mice enabled not only sexing but also the identification of 39, XO karyotype by the lack of Y chromosome. Actually, when fluorescence activated cell sorting (FACS) was applied to Y-GFP ES cells, non-fluorescent ES cells were conveniently collected and showed the lack of Y chromosome by PCR genotyping and Southern blot analysis. FACS analysis revealed Y chromosome loss occurred at 2.9 % of 40, XY ES cells after five passages. These Y-GFP ES cells are potentially applicable to reduce the time, cost and effort needed to generate the gene-targeted mice by the production of male and female mice derived from the same ES cell clone.

Clinical significance of left ventricular apical aneurysms in hypertrophic cardiomyopathy patients: the role of diagnostic electrocardiography.

OBJECTIVES: Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular apical aneurysm, leading to serious cardiovascular complications. The aims of this study were to identify the incidence and clinical course of HCM patients with apical aneurysms in Japan, and to evaluate the role of electrocardiography (ECG) as a screening test to detect apical aneurysms in HCM patients. METHODS AND RESULTS: In a retrospective, single center analysis of a population of 247 HCM patients, 21 patients (8.5%) had left ventricular apical aneurysms. Their mean age was 60 ± 14 years (range: 23-77 years) at study entry. Over 4.7 ± 3.3 years of follow-up, 10 patients (47.6%) experienced an adverse clinical event (annual event rate: 10.1%/y), including five implantable cardioverter-defibrillator (ICD) implantations for ventricular tachycardia/ventricular fibrillation (VT/VF), an appropriate discharge of ICD for VT/VF, and four nonfatal thromboembolic strokes. Two patients developed systolic dysfunction (ejection fraction <50%). No sudden cardiac death or progressive heart failure was detected. Fourteen patients showed ST-segment elevation (≥ 1 mm) in V3 through V5 of ECG. In four patients, progression of the ST-segment elevation was recognized. When the ST-segment elevation was used to identify apical aneurysms in HCM patients, the sensitivity was 66.7%, and the specificity was 98.7%. CONCLUSION: Apical aneurysms in HCM patients in Japan are not rare, and are associated with serious cardiovascular complications. The early diagnosis of apical aneurysms can be achieved by serial ECG.

Left ventricular apical and atrial appendage thrombus with hypertrophic cardiomyopathy in sinus rhythm: a case report.

A 47-year-old female with a history of untreated hypertension and diabetes mellitus was referred because of a left ventricular echocardiographic mass with congestive heart failure. At the time of admission, she had already had a cardio-embolic stroke with loss of recent memory and slight paralysis of the right upper arm. It was difficult to distinguish between thrombus and tumor. However, her clinical condition required surgical resection as soon as possible. We performed cardiac CT to evaluate the coronary arteries and to scan the mass at the left ventricular apex. This CT evaluation revealed another mass at the left atrial appendage. Thus, these two masses were highly suggestive of thrombi. Subemergency surgical resection of the two masses and a part of the myocardium at the left ventricular apex was successfully performed. The pathological results showed that both the mass in the left ventricular apex and the mass in the left atrial appendage were thrombi, and the myocardial disarray confirmed the echocardiographic diagnosis as hypertrophic cardiomyopathy.

Effectiveness of bromocriptine treatment in a patient with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening disorder that occurs in late pregnancy or the early puerperium despite optimal medical therapy. Recently, oxidative stress-mediated generation of antiangiogenic and proapoptotic 16-kDa prolactin, and subsequent impaired cardiac microvascularization have been related to PPCM. In turn, prolactin blockade with bromocriptine has been proven successful in preventing the onset of PPCM in mice and in patients at high risk for the disease. Here, we report the efficacy of bromocriptine for treatment of a patient with PPCM.

Circulating endothelial progenitor cells in congestive heart failure.

BACKGROUND: Endothelial progenitor cells (EPCs) circulate in the adult peripheral blood and contribute to neovascularization. EPCs are considered to be included in CD34 positive mononuclear cells (CD34+ MNCs). Kinetics of circulating EPCs in congestive heart failure (CHF) has not been fully investigated. METHODS: We determined the numbers of white blood cells (WBCs), plasma brain natriuretic peptide (BNP), serum erythropoietin, vascular endothelial growth factor (VEGF) and thrombomodulin levels in 16 mild CHF patients (NYHA I, II), 10 severe CHF patients with acute exacerbation (NYHA III, IV), and 22 control subjects. The number of CD34+ MNCs in peripheral blood was quantified by flow cytometry. RESULTS: The ratio of CD34+ MNCs:10(3) WBCs in mild CHF patients was higher than that in control subjects (P<0.05). Interestingly, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients at admission was significantly lower than that in control subjects (P<0.005) or in mild CHF patients (P<0.05). Levels of BNP and erythropoietin in severe CHF patients were significantly higher than those in mild CHF patients. However, VEGF and thrombomodulin levels were not different between mild and severe CHF patients. In addition, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients increased in proportion to the amelioration of CHF during hospitalization, and this increase correlated with the decrease in BNP level. CONCLUSIONS: The ratio of CD34+ MNCs:10(3) WBCs was decreased in severe CHF. These findings suggest that impaired EPC recruitment might be involved in the pathophysiology of severe CHF.

[Questionary research on individual psychotherapy of borderline personality disorder (BPD)].

The authors researched individual psychotherapy of borderline personality disorder (BPD) in Japan using a questionnaire given to expert therapists. To select the expert therapists, a database search for the keywords "borderline personality disorder" and "border-line case" was carried out in the Japanese literature on psychiatry and clinical psychology. Thus, 280 expert therapists, who were authors of articles related to the psychotherapy of BPD, were selected. Qestionnaires on individual psychotherapy of BPD were sent to them, and 128 responses were obtained. About 60% of these therapists were performing structured individual psychotherapy. This was about half of the psychiatrists and almost all of the clinical psychologists. Most of the structured psychotherapy was performed once a week, with 50 minute sessions. But there also were biweekly, 30-39 minute, 40-49 minute, and 20-29 minute sessions. The basic therapeutic methodology was psychoanalytic psychotherapy, supportive psychotherapy, and eclectic therapy, with each of them constituting about one third of the total, in this order of percentage. In the case of structured individual psychotherapy, what the majority of the therapists performed is as follows. They talked about therapeutic goals. When talking about therapeutic goals, the focus was on realistic issues such as improving social adaptation, controlling impulsive behavior or reducing the symptoms. In the face of self-harm behavior, they talked about the meaning and the utility of self-harm behavior, listened to the progression of the episodes, or said it was definitely not a good thing to do. If the self-harm behaviors were repeated, they told the patients that it was necessary for them to be confined to the closed-ward, or told them that the continuation of psychotherapy might become difficult. When there was intense anger toward the therapists, they validated the rightful parts of it. Concerning the anger and depression of the therapists, they restrained their feelings and considered them later, talked about it with their colleagues and experts, or communicated to the patients their honest feelings. In the case of frequent telephone calls, they told their patients to reduce their calls as much as possible, but when the calls came, talked with them briefly. Or they allotted the times the patients could make a call. Disclosure of the private information of the therapists was not done at all, or was done sometimes according to the situation. They actively talked about the limitations of the therapists and the patient-therapist relationship. They appreciated and praised the achievements of the patients. They talked about the termination of the psychotherapy. When they happened to meet the patients outside of the therapy, they responded to the patients only when they were addressed, or they addressed the patients by themselves but just briefly. The clinical situation of the BPD individual psychotherapy in Japan was not made clear so far. Our research clarified the situation, though there was the methodological limitation of the questionnaire research.

An anti-ulcer drug, geranylgeranylacetone, suppresses inducible nitric oxide synthase in cultured vascular smooth muscle cells.

OBJECTIVE: Geranylgeranylacetone (GGA) is commonly used as an anti-ulcer drug. If GGA affects inducible nitric oxide synthase (iNOS) in the vascular tissue, it could influence disease progression in coronary arteries. We investigated the effects of the anti-ulcer drug GGA on iNOS activity in vascular smooth muscle cells. METHODS: We measured the production of nitrite, a stable metabolite of nitric oxide, in cultured rat vascular smooth muscle cells with the Griess reagent. iNOS protein and mRNA expressions were assayed by western blotting and northern blotting, respectively. The levels of nuclear factor (NF)-kappaB proteins in nuclear extracts were analyzed by gel retardation assay. Heat shock protein 70, a cytoprotective molecule, was evaluated by western blotting. RESULTS: Incubation of cultures with interleukin-1beta for 24 h caused a significant increase in nitrite generation. Interleukin-1beta-induced nitrite production by vascular smooth muscle cells was significantly suppressed by GGA in a dose-dependent manner. GGA-suppressed nitrite production was accompanied by decreased iNOS mRNA and protein accumulations. GGA by itself did not modulate the basal level of nitrite production. Interleukin-1beta induced NF-kappaB activation in vascular smooth muscle cells, and the addition of GGA further inhibited this NF-kappaB activation. GGA itself induced heat shock protein 70 expression in a dose-dependent manner. CONCLUSION: These findings demonstrated that GGA suppresses iNOS expression in cytokine-stimulated cultured vascular smooth muscle cells partially through the suppression of NF-kappaB activation, suggesting that GGA may modulate the pathophysiology of cardiovascular diseases including atherosclerosis. In addition, this effect may be associated with heat shock protein 70 production by GGA.

Identification of a specific molecular repressor of the peroxisome proliferator-activated receptor gamma Coactivator-1 alpha (PGC-1alpha).

The nuclear co-activator PGC-1alpha is a pivotal regulator of numerous pathways controlling both metabolism and overall energy homeostasis. Inappropriate increases in PGC-1alpha activity have been linked to a number of pathological conditions including heart failure and diabetes mellitus. Previous studies (Puigserver, P., Adelmant, G., Wu, Z., Fan, M., Xu, J., O'Malley, B., and Spiegelman, B. M. (1999) Science 286, 1368-1371) have demonstrated an inhibitory domain within PGC-1alpha that limits transcriptional activity. Using this inhibitory domain in a yeast two-hybrid screen, we demonstrate that PGC-1alpha directly associates with the orphan nuclear receptor estrogen-related receptor-alpha (ERR-alpha). The binding of ERR-alpha to PGC-1alpha requires the C-terminal AF2 domain of ERR-alpha. PGC-1alpha and ERR-alpha have a similar pattern of expression in human tissues, with both being present predominantly in organs with high metabolic needs such as skeletal muscle and kidney. Similarly, we show that in mice physiological stimuli such as fasting coordinately induces PGC-1alpha and ERR-alpha transcription. We also demonstrate that under normal conditions PGC-1alpha is located within discrete nuclear speckles, whereas the expression of ERR-alpha results in PGC-1alpha redistributing uniformly throughout the nucleoplasm. Finally, we show that the expression of ERR-alpha can dramatically and specifically repress PGC-1alpha transcriptional activity. These results suggest a novel mechanism of transcriptional control wherein ERR-alpha can function as a specific molecular repressor of PGC-1alpha activity. In addition, our results suggest that other co-activators might also have specific repressors, thereby identifying another layer of combinatorial complexity in transcriptional regulation.