Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6). Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies

Terahertz wireless communication at 560-GHz band using Kerr micro-resonator soliton comb

Terahertz (THz) waves have attracted attention as carrier waves for next-generation wireless communications (6G). Electronic THz emitters are widely used in current mobile communications; however, they may face technical limitations in 6G with upper-frequency limits. We demonstrate wireless communication in a 560-GHz band by using a photonic THz emitter based on photomixing of a 560-GHz-spacing soliton microcomb in a uni-travelling carrier photodiode together with a THz receiver of Schottky barrier diode. The on-off keying data transfer with 2-Gbit/s achieves a Q-factor of 3.4, thus, satisfying the limit of forward error correction.Comment: 17 pages, 4 figur

Terahertz wireless communication in a 560-GHz band using a Kerr micro-resonator soliton comb

Terahertz (THz) waves have attracted attention as carrier waves for next-generation wireless communications (6 G). Electronic THz emitters are widely used in current mobile communications; however, they may face technical limitations in 6 G with upper-frequency limits. We demonstrate wireless communication in a 560-GHz band by using a photonic THz emitter based on photomixing of a 560-GHz-spacing soliton microcomb in a uni-travelling carrier photodiode together with a THz receiver of Schottky barrier diode. The on-off keying data transfer with 2-Gbit/s achieves a Q-factor of 3.4, thus, satisfying the limit of forward error correction

Wireless data transmission in a 560-GHz band using low-phase-noise terahertz wave generated by photomixing of a pair of distributed feedback lasers injection-locking to Kerr micro-resonator soliton comb

The demand for higher data rates in next-generation mobile wireless communication systems (6G) has led to significant interest in terahertz (THz) waves as a high-frequency, broad modulation bandwidth carrier wave. In this study, we propose and demonstrate a wireless data transfer in the 560-GHz band using low-phase-noise THz waves generated by photomixing of a pair of distributed feedback lasers injection-locking to Kerr micro-resonator soliton comb. Experimental results showed near-error-free on-off keying (OOK) data transfer at 1 Gbit/s in the 560-GHz band, with a Q-factor of 6.23, surpassing the error-free limit. Also, modulation formats of binary phase shift keying (BPSK) and quadrature phase shift keying (QPSK) were successfully used, showing clear constellation diagrams and relatively low root mean squared error vector magnitude (rms EVM) values of 23.9% and 23.6%, respectively. Moreover, data transfer at 0.4 Gbit/s in 16 quadrature amplitude modulation (16QAM) demonstrated clear isolated symbols and achieved a low rms EVM value of 8.1%, complying with the IEEE 802.15.3d standard amendment. These demonstrations highlight the potential of using injection-locked DFB lasers with the Kerr micro-resonator soliton comb to achieve high-quality, high-speed wireless data transfer in the 560-GHz band. These findings contribute significantly to the advancement of wireless communication technology in the THz frequency range and pave the way for the realization of 6G wireless communication systems

Carrier conversion from terahertz wave to dual-wavelength near-infrared light injection-locking to optical comb using asynchronous nonpolarimetric electro-optic downconversion with electro-optic polymer modulator

THz waves are promising wireless carriers for next-generation wireless communications, where a seamless connection from wireless to optical communication is required. In this study, we demonstrate carrier conversion from THz waves to dual-wavelength NIR light injection-locking to an optical frequency comb using asynchronous nonpolarimetric electro-optic downconversion with an electro-optic polymer modulator. THz wave in the W band was obtained as a stable photonic RF beat signal of 1 GHz with a signal-to-noise ratio of 25 dB via the proposed THz-to-NIR carrier conversion. In addition, the results imply the potential of the photonic detection of THz waves for wireless-to-optical seamless communication.Comment: 15 pages, 5 figure

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study. Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r s = 0.531, P = 1.032 × 10−4). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

Change of prescription for patients with schizophrenia or major depressive disorder during admission : real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project

Background Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. Methods Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. Results For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. Conclusions It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures

Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs

EGUIDE project and treatment guidelines

Background Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. Aims The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. Method A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. Results All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. Conclusions All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists