We report on two cases of patients with chronic pain treated with opioid analgesics. They did not continue their treatment with opioid because of side effects.
An 88 year-old female complained of low back and leg pain caused by lumbar spinal canal stenosis. She also complained of dizziness, nausea and appetite loss after a course of weak oral opioid was administered. We thought it necessary to improve her general condition and digestive sickness following treatment for pain, and administered 5 g/day of hangebyakujutsutemmato. After the administration of this hangebyakujutsutemmato, her general condition improved, and we could administer various analgesics.
A 62 year-old female complained of dull headache, right neck pain and stiffness of tear and mouth due to fibromyalgia and collagen disease dating back several years. Her pain was reduced by the combined administration of a strong opioid and an immunosuppressive agent. However, she complained of severe dizziness, nausea and appetite loss after the commencement of drug therapy. Her general condition improved markedly, through the administration of 5 g/day of hangebyakujutsutemmato, and she was able to continue her treatment of chronic pain without deleterious events.
In conclusion, in patients treated with opioids for chronic pain, dizziness, dull headache, nausea, vomiting and loss of appetite is often seen. Therefore, we emphasize that the combined administration of hangebyakujutsutemmato and opioids can be beneficial for the treatment of chronic pain patients.

An 80-year-old man felt a loss of strength and sharp pain in both lower limbs while playing gate-ball, consulted a nearby doctor, and was followed up. Because the sharp pains in both lower limbs became aggravated the next day, he was given a previously prescribed medication. Both femoral pulses were absent and acute arterial obstruction of the lower limbs was suspected. A contrast-enhanced CT scan showed a thrombosed infrarenal abdominal aortic aneurysm with a maximum transverse diameter of 37 mm, and both external iliac arteries were contrast imaged by collateral circulation pathways. We diagnosed acute thrombosis of an abdominal aortic aneurysm, and was urgently transported to our hospital. We classified his lower limbs as Balas grade III and TASC classification grade IIb and Rutherford classification grade IIb. He exhibited no abdominal symptoms and since we confirmed the blood flow of his lower limbs, we decided to perform revascularization. An extra-anatomical bypass (axillo-bifemoral bypass) was conducted because he had dementia, and was old. After the operation, myonephropathic metabolic syndrome (MNMS) did not develop, and the patient was discharged on foot on the 16th postoperative day. Acute thrombosis of an abdominal aortic aneurysm is a rare disease. Because the ischemic area widens, often causing serious MNMS after the revascularization, it has a poor prognosis. Here, we report a case in which one such patient was rescued.

In this study, we investigated whether a difference in the angular velocity has an effect on proprioceptive sensibility in 30 healthy subjects. Knee detection of passive motion at five angular velocities (0.1°/s, 0.2°/s, 0.3°/s, 0.4°/s, and 0.5°/s) was carried out from a starting position of 15° knee flexion for extension using a proprioception testing device. At 0.1°/s, the elapsed time was longer than that of the other angular velocities and the angular displacement was bigger as well. There were no significant differences among the remaining angular velocities (0.2～0.5°/s). Therefore it is suggested that a healthy knee has less proprioception at an angular velocity of 0.1°/s.

Objective: This study aimed to verify the utility of simple, safe, and effective venous thromboembolism (VTE) prophylaxis and implement it with few adverse events during cesarean delivery. Methods: This single-center, prospective study involved pregnant women who underwent cesarean deliveries from August 3, 2020 to March 31, 2022. Patients with VTE risk factors were initially administered unfractionated heparin (5,000 international unit [IU] subcutaneously, twice daily), 6 hours after cesarean delivery. Subsequently, they were administered enoxaparin (2,000 IU subcutaneously, twice daily). They were not administered anticoagulants if one or more of the exclusion criteria were met. The primary efficacy outcome was the incidence of symptomatic VTE. The primary safety outcome was the incidence of major bleeding. Results: Out of the 850 women eligible for this study, 551 (64.9%) had one or more VTE risk factors and 299 (35.1%) had no risk factors. Of the 551 women with one or more VTE risk factors, 15 met one or more exclusion criteria for enoxaparin administration. A total of 314 women received only perioperative mechanical prophylaxis, including 15 who met the exclusion criteria for anticoagulants and 299 without VTE risk factors. During implementation of the protocol, no woman developed symptomatic VTE after cesarean delivery. Major bleeding occurred in only one woman who received postoperative anticoagulants. Conclusion This protocol, which clarified the administration of anticoagulants according to VTE risk factors and dose reduction/discontinuation criteria, may be an effective and safe VTE prophylaxis for cesarean deliveries.

MHLW released a guideline for Risk Management Plan (RMP) in April 2012, in order to manage the risk of pharmaceutical products from the development stage towards post marketing period. The guideline suggests to determine Safety Specification and to develop Pharmacovigilance Plan (PVP) and Risk Minimization Plan aligned to the ICH E2E guideline. However, in some of the RMPs, which had been published online (as of August 2014), conventional (Special) Drug Use Results Surveys are planned as a “universal” PVP regardless of the impact, severity and characteristics of the risks. Our JPMA taskforce (Data Science Expert Committee) summarized report and published in August 2014. In this report, we explained how to evaluate safety events based on evidence level for safety specification and how to develop PVP. Also, we would like to propose KAIZEN activities for RMP improvement as follows:
1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully.
2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development.
3. Safety profiles should be discussed thoroughly on DSUR development among stakeholders in order to clarify safety specification at NDA. Research questions for each different risk and missing information should be established according to PECO, which will flow into appropriate PVP planning.
4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s).
We expect all stakeholders, including clinical development specialists in industry, regulatory authorities, and academia, to have better understating of RMP principle and to manage and implement it more appropriately in a scientific manner.

An abdominal advancement flap (AAF) is a flap that pulls the elevated abdominal skin up and creates the shape of the inferior portion of the breast by making a neo-inframammary fold. Seven patients underwent remodeling using an AAF or a method combining an AAF with other volume displacement techniques after partial mastectomy. The excision volume ranged from 15% to 35%. AAF with only mobilization of the gland flaps was performed in two cases, with lateral mammoplasty in one case, with the round block technique (RBT) in one case, with a modified RBT in one case, and with medial mammoplasty in two cases. Although one patient treated with a RBT had a partial blood-flow insufficiency of the nipple-areola complex, it improved with conservative treatment. The cosmetic results were found to be excellent in three cases, good in three, and fair in one case.
Breast ; Cosmetics ; Displacement (Psychology) ; Female ; Humans ; Mammaplasty ; Mastectomy, Segmental ; Skin ; Surgical Procedures, Operative

We introduce a method combining two oncoplastic techniques for breast-conserving reconstruction. The procedure is as follows: first, an extended glandular flap is made by undermining the breast from both the skin and the pectoralis fascia to the upper edge of the breast at the subclavicular area. After modeling the breast mound with the extended glandular flap, an inframammary adipofascial flap is made. The flap is reflected back to the breast area remodeled using the extended glandular flap. After reshaping the breast, the inframammary line is then re-shaped. This method is indicated for patients with breast cancer in the outer portion of the breast, who have small dense breasts, and have undergone a large excision of about 40% of their breast volume. We treated four patients, all of whom had either excellent or good cosmetic results with no fat necrosis.
Breast ; Breast Neoplasms ; Cosmetics ; Fascia ; Fat Necrosis ; Female ; Humans ; Mammaplasty ; Mastectomy, Segmental ; Skin

PURPOSE: Although various strategies have been reported, there are no defined criteria for cosmetic evaluation methods after breast-conserving surgery (BCS). Since Asians tend to have smaller breasts, indistinct inframammary folds, and conspicuous scars, differences in the cosmetic results are expected. So we examined two subjective methods and one objective method to determine the differences, and elements necessary for a cosmetic evaluation after BCS. METHODS: Frontal photographs of 190 Japanese were evaluated using the Harris scale (Harris) and the evaluation method proposed by the Japanese Breast Cancer Society Sawai group (Sawai group) as the subjective methods, and the Breast Cancer Conservation Treatment cosmetic results (BCCT.core) as the objective method, respectively. In order to examine the necessary elements for developing a new ideal method, 100 out of 190 were selected and assessed separately by six raters using both the Harris and modified Sawai group methods in the observer assessment. The correlation between the two methods was examined using the Spearman rank-correlation coefficient. RESULTS: The results of the BCCT.core and the other two methods were clearly different. In the observer assessment, the consensuses of the six raters were evaluated as follows: 27, 27, 26, and 20 cases were evaluated as "excellent," "good," "fair," and "poor," respectively. For the Spearman rank-correlation coefficient, values higher than 0.7 indicated a strong correlation, as seen by the values of 0.909 for the breast shape and 0.345 for the scar. The breast shape accounted for the most significant part of the evaluation, and the scar had very little correlation. CONCLUSION: In this study, we recognized a clear difference between the subjective and objective evaluation methods, and identified the necessary elements for cosmetic evaluation. We would like to continue developing an ideal cosmetic evaluation that is similar to subjective one and is independent from raters.
Asian Continental Ancestry Group* ; Breast ; Breast Neoplasms ; Cicatrix ; Consensus ; Esthetics ; Humans ; Mastectomy, Segmental*

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

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.