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In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium × phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium × phosphate product of <55 mg2/dL2 was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5–5.5 mg/dL) or iPTH (150–300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium × phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease. [ABSTRACT FROM AUTHOR]

The article discusses research which hypothesized that adjunctive ramelteon with antipsychotics would be more effective for delirium than antipsychotics monotherapy. Topics discussed include the clinical definition of delirium and ramelteon, which is an agonist of melatonin receptor, the study population which were divided into two groups, the adjunctive ramelteon and the anitpsychotics monotherapy group, and the implications of the research findings.

Background and Objectives: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T 50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T 50 value than a vitamin D receptor activator maxacalcitol., Design, Setting, Participants, & Measurements: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µ g thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T 50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively., Results: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n =167; control, n =159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T 50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the etelcalcetide group. The increase in T 50 value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P =0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score., Conclusions: Etelcalcetide was more effective in increasing T 50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs., Clinical Trial Registry Name and Registration Number: VICTORY; UMIN000030636 and jRCTs051180156., (Copyright © 2021 by the American Society of Nephrology.)

Study Objectives: The cyclic sequence of NREM and REM sleep, the so-called ultradian rhythm, is a highly characteristic feature of sleep. However, the mechanisms responsible for the ultradian REM sleep rhythm, particularly in humans, have not to date been fully elucidated. We hypothesize that a stage transition mechanism is involved in the determination of the ultradian REM sleep rhythm., Participants: Ten healthy young male volunteers (AGE: 22 ± 4 years, range 19-31 years) spent 3 nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet), a central serotonergic and dopaminergic antagonist, 30 min before the polysomnography recording., Measurements and Results: We measured and investigated transition probabilities between waking, REM, and NREM sleep stages (N1, N2, and N3) within the REM-onset intervals, defined as the intervals between the onset of one REM period and the beginning of the next, altered by risperidone. We also calculated the transition intensity (i.e., instantaneous transition rate) and examined the temporal pattern of transitions within the altered REM-onset intervals. We found that when the REM-onset interval was prolonged by risperidone, the probability of transitions from N2 to N3 was significantly increased within the same prolonged interval, with a significant delay and/or recurrences of the peak intensity of transitions from N2 to N3., Conclusions: These results suggest that the mechanism governing NREM sleep stage transitions (from light to deep sleep) plays an important role in determining ultradian REM sleep rhythms.

Background: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS; yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in patients with dementia and borderline personality disorder. We aimed at evaluating both the efficacy and safety of YGS in patients with treatment-resistant schizophrenia., Methods: Thirty-four patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (YGS-free) group (n = 25) and treated in a 4-week open-label study with YGS at an average daily dosage of 6.7 +/- 2.5 g (range, 2.5-7.5 g). Psychometric instruments used to assess efficacy included the Positive and Negative Syndrome Scale for Schizophrenia and the Drug-Induced Extrapyramidal Symptom Scale., Results: A significant decrease was observed at 2 weeks and at 4 weeks in each Positive and Negative Syndrome Scale for Schizophrenia subscale score in the YGS group, but this was not observed in the control group. However, the Drug-Induced Extrapyramidal Symptom Scale total score did not change in both groups., Conclusions: In this open-label pilot study, patients treated with YGS showed a statistically significant reduction on clinician-rated scales. The present findings suggest that an adjunction of YGS might be effective for treatment-resistant schizophrenia.

Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase, and has been shown to delay disease in a mouse model of neuropsychiatric disorders. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline (150 mg/d) for 4 weeks as an open-label adjunct to antipsychotic medication to 22 patients with schizophrenia. The Positive and Negative Syndrome Scale for schizophrenia showed statistically significant and robust clinical improvements with minocycline treatment, which were maintained at follow-up evaluation 4 weeks after the end of minocycline treatment. There were no adverse events. These results suggest that minocycline may be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia.

We investigate a novel class of neural stochastic resonance (SR) exhibiting error-free information transfer. Unlike conventional neural SR, where the decrease of a system's response with too much noise is associated with an increase in the baseline firing rate, here the bell-shaped SR behavior of the input-output cross correlation emerges versus increasing input noise in spite of no significant increase of the baseline firing rate. The neuron thus acts as an error-free detector for weak signals. An integrate-and-fire model with short-term synaptic depression convincingly validates our experimental findings for SR in the human tactile blink reflex.

Objective: In the treatment of depression, clinical and psychopharmacologic aspects have been investigated to predict the response to anti-depressants. Some trials have reported clinical improvement as early as the first week; however, few have investigated the early effects of selective serotonin reuptake inhibitors. The aim of this study was to investigate therapeutic efficacy of paroxetine within the first 3 days of therapy onset., Method: Subjects included 29 outpatients diagnosed at first interview with major depressive disorder according to DSM-IV criteria (June 2003 to January 2007). Paroxetine 5-20 mg/day was administered for at least 2 weeks. Treatment efficacy was defined as a > 50% decrease in Hamilton Rating Scale for Depression (HAM-D) total scores from baseline to the end of the second week. To determine efficacy within the first 3 days, patients completed the HAM-D as a self-rated questionnaire on the first and third days and at the end of the first, second, and fourth weeks., Result: Subjects were divided into 2 groups: successful (17 responders) and failed (12 non-responders). There was a significant difference between the reduction rates of self-rated HAM-D total scores on the third day (p < .01)., Conclusion: In patients responding to paroxetine in the early stages of treatment, the prediction of response within the first 3 days using the self-rated HAM-D is suggested.