Chie Usui

Preventive Effects of Ramelteon on Delirium: A Randomized Placebo-Controlled Trial

IMPORTANCE No highly effective interventions to prevent delirium have been identified. OBJECTIVE To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium. DESIGN, SETTING, AND PARTICIPANTS A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital. Eligible patients were 65 to 89 years old, newly admitted due to serious medical problems, and able to take medicine orally. Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours. INTERVENTIONS Sixty-seven patients were randomly assigned using the sealed envelope method to receive ramelteon (8 mg/d; 33 patients) or placebo (34 patients) every night for 7 days. MAIN OUTCOMES AND MEASURES Incidence of delirium, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). RESULTS Ramelteon was associated with a lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09 (95% CI, 0.01-0.69). Even after risk factors were controlled for, ramelteon was still associated with a lower incidence of delirium (P = .01; odds ratio, 0.07 [95% CI, 0.008-0.54]). The Kaplan-Meier estimates of time to development of delirium were 6.94 (95% CI, 6.82-7.06) days for ramelteon and 5.74 (5.05-6.42) days for placebo. Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon than in those taking placebo (χ(2) = 9.83; P = .002). CONCLUSIONS AND RELEVANCE Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium. TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000005591.

Electroconvulsive therapy improves severe pain associated with fibromyalgia

Abstract The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper‐responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium‐99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck’s depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.

Effectiveness of second-generation antipsychotics with acute-phase schizophrenia

PURPOSE Although olanzapine may have advantages over other second-generation antipsychotics (SGAs) regarding longer time to treatment discontinuation among chronically ill patients, little evidence has been provided for the comparative effectiveness of SGAs in the acute phase. We aimed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients. We performed a rater-blinded, randomized controlled trial of four SGAs in 15 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A final total of 78 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20), olanzapine (10-20 mg/day; n=17), quetiapine (300-750 mg/day; n=20), or aripiprazole (12-30 mg/day; n=21), with follow-up at 8 weeks. The primary outcome measure was all-cause treatment discontinuation. RESULTS Overall, 37% (29/78) of patients discontinued the study medication before 8 weeks: 25% for risperidone; 12% for olanzapine; 55% for quetiapine; and 52% for aripiprazole. Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine (p=0.006) or aripiprazole (p=0.008) groups, but not compared to the risperidone group (p=0.32). Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group (p=0.048), but not compared to the aripiprazole group (p=0.062). However, the rate of p.r.n. intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups (p=0.029). CONCLUSION Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients.

Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study.

Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting.

No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients.

SummaryGenetic mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene on the chromosome 1p cause susceptibility to autosomal dominant hypercholesterolemia (Abifadel et al., 2003; Leren, 2004; Timms et al., 2004). Variants of PCSK9 encoding neural apoptosis regulated convertase-1

An epidemiologic internet survey of fibromyalgia and chronic pain in Japan.

To determine the epidemiologic features and symptom characteristics of fibromyalgia (FM) in Japan, and compare them with those for other chronic pain (CP) diagnoses.

The Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and the Fibromyalgia Symptom Scale: reliability and validity

The aim of this study was to investigate the reliability and the validity of the Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010-J), and its quantification scale, the Fibromyalgia Symptom Scale (FS-J). In this study, we divided patients with chronic pain without psychiatric disorders other than depression into two groups according to the 1990 ACR Diagnostic Criteria for Fibromyalgia, a fibromyalgia group and a non-fibromyalgia group (rheumatoid arthritis, osteoarthritis, and gout). Patients in both groups were assessed using the ACR 2010-J and FS-J. Seventy-seven of 94 (82%) patients in the fibromyalgia group met the ACR 2010-J, whereas 9% (4/43) of the non-fibromyalgia group did so, with a sensitivity of 82%, specificity of 91%, positive predictive value of 95%, negative predictive value of 70%, and positive likelihood ratio of 8.8. Mean total scores on the FS-J significantly differentiated the fibromyalgia from the non-fibromyalgia group. The scale had high inter-rater reliability and high internal consistency. With a cutoff score of 10, the positive likelihood ratio was 10.1. Our findings indicate that the ACR 2010-J and FS-J have high reliability and validity, and are useful for assessing fibromyalgia in Japanese populations with chronic pain. As regards the positive likelihood ratio, that of the FS-J might be suitable as a positive test.

Maximal Response to Electroconvulsive Therapy for the Treatment of Catatonic Symptoms

Objectives: Because the number of medical lawsuits has recently increased in Japan, doses of medication above the upper limits have recently been avoided, even when treating catatonic patients. We treated catatonic symptoms with drugs within the upper limit of dosage and electroconvulsive therapy (ECT) to determine the maximal response. Methods: We examined 50 consecutive patients with catatonic symptoms admitted to a university hospital during a 32-month period who were treated with either drugs within the upper limit or ECT. Results: Response rates were as follows: ECT, 100%; chlorpromazine, 68%; risperidone, 26%; haloperidol, 16%; and benzodiazepines, 2%. Conclusions: The findings indicated that ECT is the treatment of choice for catatonic symptoms.

No Genetic Association between the Myeloperoxidase Gene –463 Polymorphism and Estrogen Receptor-α Gene Polymorphisms and Japanese Sporadic Alzheimer’s Disease

Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques and contributes to Alzheimer’s disease (AD) pathology through oxidation-induced damage. MPO activity is normally higher in women than in men. Additionally, a functional biallelic (G/A) polymorphism in the promoter region (–463) of the MPO gene has been associated with a gender-specific risk factor for AD, but reports of this association have been inconsistent. Furthermore, estrogen is known to enhance MPO activity in myeloid cells and increases the amount of MPO in plasma. Recently, estrogen replacement therapy has been reported to reduce the risk of developing AD and to help maintain cognitive function in patients with AD. In the current study, we analyzed the MPO –463 polymorphism and two estrogen receptor-α polymorphisms in 205 Japanese sporadic AD patients and 92 controls. The results suggest that there is no significant difference in the genotypic frequencies and allelic frequencies of the MPO –463 polymorphism and the estrogen receptor-α polymorphisms between the Japanese sporadic AD group and the control group.

Irreversible Subcortical Dementia Following High Altitude Illness

In this report, we present the cases of two 63-year-old women who developed high altitude cerebral edema complicated by the occurrence of permanent neuropsychiatric sequelae. They shared a similar clinical course, in that both developed disturbance of consciousness shortly after their arrival at Cuzco, Peru (3500 m), and both developed persistent neuropsychiatric symptoms after resolution of the acute illness. Interestingly, in case 2 there was a 1-month lucid interval between remission of high altitude illness and occurrence of the irreversible neuropsychiatric sequelae. Brain computerized tomography in case 1 and brain magnetic resonance imaging in case 2 disclosed lesions in the globus pallidus bilaterally, suggesting that the neuropsychiatric symptoms in these patients were manifestations of subcortical dementia. The development of high altitude illness was considered to be attributable to mild restrictive lung impairment in case 1 and to a deficient ventilatory response to hypoxia in case 2. It must therefore be borne in mind that irreversible subcortical dementia may be associated with high altitude cerebral edema.