1.A Systematic Review and Meta-Analysis of Systemic Corticosteroids for the Palliation of Dyspnea in Patients with Cancer
Kozue SUZUKI ; Hideki KATAYAMA ; Hiroyuki KOHARA ; Yoshinobu MATSUDA ; Sho GOYA ; Jun KAKO ; Yoko KASAHARA ; Masanori MORI ; Takeo NAKAYAMA ; Hiroaki WATANABE ; Takashi YAMAGUCHI
Palliative Care Research 2025;20(2):95-102
Objective: Almost half of all patients with cancer experience dyspnea, which can have various causes. Although systemic corticosteroids are administered to relieve symptoms, their efficacy has not been established. This systematic review aims to determine the efficacy of systemic corticosteroids for dyspnea in patients with cancer. Methods: CENTRAL, MEDLINE, EMBASE, and Ichushi-Web databases were searched for articles published from their inception to September 23, 2019, on studies of systemic corticosteroid administration for dyspnea in patients with cancer. The primary outcome measure was dyspnea intensity, as assessed by patient-reported outcomes. Secondary outcome measures were quality of life, delirium, and severe adverse events. Results: Two RCTs were included in the meta-analysis. With regard to alleviating dyspnea, the systematic corticosteroid group was associated with significantly greater dyspnea relief than the placebo group (mean difference: −0.71 [95% CI: −1.4 to −0.03]). However, a meta-analysis of quality of life and delirium could not be performed due to insufficient data. Analysis of severe adverse events showed no significant difference in their incidence between the corticosteroid and control groups (relative rate: 0.96 [95% CI: 0.19-4.93]). Conclusions: Systemic corticosteroids may be effective in treating dyspnea in patients with cancer, particularly those with lung involvement. Limiting the conditions for which corticosteroids are approved is expected to promote their appropriate use and minimize their adverse effects. However, further investigation is needed to determine the appropriate dosage, and the conditions in which corticosteroids are effective.
2.Study on Adherence and Safety of Patients Taking Molnupiravir Capsules
Yukiko FUKUDA ; Kouichi HOSOMI ; Shouhei OKANO ; Takahiro YAMAGUCHI ; Hirohisa SHINDOU ; Daichi OKUDA ; Takashi MURATA
Japanese Journal of Social Pharmacy 2024;43(1):40-47
To assess the safety of molnupiravir capsules (MOV) and the adherence of patients taking these capsules, we conducted a survey of patients who were dispensed MOV at the Maruzen Pharmacy from January 1st to September 30th, 2022. In the survey, a sample of 134 patients were requested to complete a questionnaire, from whom we received 56 responses (response rate: 41.8%). Among the respondents, 11 (19.6%) failed to complete their medication, and those aged 60 years or older tended to have poor adherence (P<0.001). Apart from age, we detected no statistical differences with respect to other assessed factors (gender, capsule size, occurrence of side effects, and evaluation of pharmacist’s explanations). Side effects were reported by 11 individuals (19.6%) taking the drug, although these were mainly consistent with those that have been reported in clinical trials. In addition, 20 individuals (35.7%) experienced COVID-19 after-effects after taking MOV. When requested to evaluate pharmacies and pharmacists, five individuals (8.9%) reported feeling dissatisfied. Although the results obtained in this survey are based on a limited number of patients, they do reveal a concerning lack of adherence among patients over 60 years of age; and there are needs for future improvements in the size of MOV capsules.
3.Current Status of Do-not-resuscitate Discussions for Terminal Cancer Patients in Japan
Yosuke MATSUDA ; Sachiko OHDE ; Masanori MORI ; Isseki MAEDA ; Takashi YAMAGUCHI ; Hiroto ISHIKI ; Yutaka HATANO ; Jun HAMANO ; Tatsuya MORITA
Palliative Care Research 2024;19(2):137-147
Purpose: The purpose of this study was to clarify the current status of Do-Not-Resuscitate discussions (DNRd) with terminally ill cancer patients in Japan and the psychological burden on bereaved families depending on whether or not a DNRd is performed. Method: A multicenter prospective observational study of advanced cancer patients admitted to 23 palliative care units (PCUs) in Japan was conducted, and a questionnaire survey of bereaved families was also conducted after patients died. Result: 1,605 patients were included in the analysis, and 71.4% of patients had a DNRd with doctors before PCU admission, 10.8% at admission, and 11.4% during admission. In contrast, 93.3% of family members had a DNRd with doctors before PCU admission, 48.4% at admission, and 52.1% during admission. Conclusion: Although DNRd was performed between patients and physicians in 72.3% of cases at any point throughout the course of time from before PCU admission to death, there was no evidence of psychological burden such as depression or complicated grief in the bereaved families due to patient participation in DNRd.
4.Patient-specific mechanical analysis of pedicle screw insertion in simulated osteoporotic spinal bone models derived from medical images
Norihiro NISHIDA ; Hidenori SUZUKI ; Hanvey TETSU ; Yuki MORISHITA ; Yogesh KUMARAN ; Fei JIANG ; Masahiro FUNABA ; Kazuhiro FUJIMOTO ; Yusuke ICHIHARA ; Takashi SAKAI ; Junji OHGI
Asian Spine Journal 2024;18(5):621-629
Methods:
Male and female patients with computed tomography data were selected. Dimensions of the first thoracic (T1), fourth lumbar (L4), and fifth lumbar (L5) vertebrae were measured, and bone models consisting of the cancellous and cortical bones made from polyurethane foam were created. PS with diameters of 4.5 mm, 5.5 mm, and 6.5 mm were used. T1 PS were 25 mm long, and L4 and L5 PS were 40 mm long. The bone models were secured with cement, and the MIT was measured using a calibrated torque wrench. After MIT testing, the PS head was attached to the machine’s crosshead. POS was then calculated at a crosshead speed of 5 mm/min until failure.
Results:
The L4 and L5 were notably larger in female bone models, whereas the T1 vertebra was larger in male bone models. Consequently, the MIT and POS for L4 and L5 were higher in female bone models across all PS diameters than in male bone models. Conversely, the MIT for T1 was higher in male bone models across all PS; however, no significant differences were observed in the POS values for T1 between sexes.
Conclusions
The mechanical properties of the proposed bone models can vary based on the vertebral structure and size. For accurate 3D surgical and mechanical simulations in the creation of custom-made medical devices, bone models must be constructed from patientspecific medical images.
5.The Effect of High-flow Nasal Cannula Oxygen for Dyspnea in Patients with Advanced Disease: Systematic Review
Sho GOYA ; Yasushi NAKANO ; Hiroaki TSUKUURA ; Yusuke TAKAGI ; Hiroaki WATANABE ; Yoshinobu MATSUDA ; Jun KAKO ; Yoko KASAHARA ; Hiroyuki KOHARA ; Masanori MORI ; Takeo NAKAYAMA ; Takashi YAMAGUCHI
Palliative Care Research 2023;18(4):261-269
Objective: To evaluate the efficacy of high-flow nasal cannula oxygen (HFNC) for dyspnea in patients with advanced disease. Methods: A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Ichu-shi Web. Inclusion criteria were: 1) randomized controlled trials evaluating the effect of HFNC on dyspnea; 2) aged 18 years or older with advanced disease with hypoxemia; 3) control group was conventional oxygen therapy or noninvasive positive pressure ventilation. Exclusion criteria were: 1) patients in intensive care unit, 2) weaning from ventilator. Results: Six studies (4 from database searches, and 2 from hand searches) were included. In the 2 studies evaluating short-term intervention, one showed HFNC was more efficacious, and the other conventional oxygen was more efficacious. In the 2 studies evaluating long-term interventions: one showed HFNC was more efficacious, and the other showed no significant difference. In the 2 studies evaluating the intervention during exercise, one showed HFNC was more efficacious, and the other showed no significant difference. Conclusion: HFNC may be effective for dyspnea in patients with advanced disease associated with hypoxemia.
6.Factors Requiring Midazolam in Addition to Systemic Opioids to Control Dyspnea in Cancer Patients at the End of Life
Yuka OKUDA ; Toshiyuki KURIYAMA ; Yoshi TSUKIYAMA ; Yoshinobu MATSUDA ; Takashi YAMAGUCHI ; Masanori MORI ; Toshio SHIMOKAWA ; Tomoyuki KAWAMATA
Palliative Care Research 2023;18(4):247-252
Background: Factors requiring midazolam in addition to systemic opioids to control dyspnea in cancer patients have yet to be evaluated. Methods: We retrospectively analyzed data for cancer patients who received systemic opioids to relieve dyspnea from April 2019 to July 2021 in Wakayama Medical University Hospital, Japan. Patients were divided into an opioid-alone group and an opioid plus midazolam group, according to the treatment of dyspnea. Results: The total of 107 patients included 85 patients (79.4%) in the opioid alone group and 22 patients (20.6%) in the opioid plus midazolam group. Age<60 years (p=0.004) and male sex (p=0.034) was significantly associated with the addition of midazolam. Multivariate analysis found age <60 years (OR=5.34, 95%CI: 1.66–17.21; p=0.005) was associated with the addition of midazolam. Conclusion: Age <60 years is factor requiring midazolam in addition to systemic opioids to control dyspnea in cancer patients.
7.Significance of rescue hybrid endoscopic submucosal dissection in difficult colorectal cases
Hayato YAMAGUCHI ; Masakatsu FUKUZAWA ; Takashi KAWAI ; Takahiro MURAMATSU ; Taisuke MATSUMOTO ; Kumiko UCHIDA ; Yohei KOYAMA ; Akira MADARAME ; Takashi MORISE ; Shin KONO ; Sakiko NAITO ; Naoyoshi NAGATA ; Mitsushige SUGIMOTO ; Takao ITOI
Clinical Endoscopy 2023;56(6):778-789
Background/Aims:
Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD).
Methods:
We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes.
Results:
Resection time was significantly shorter in the following order: RH-ESD (149 [90–197] minutes) >C-ESD (90 [60–140] minutes) >SH-ESD (52 [29–80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%–30%]) than in the en bloc resection group (40% [20%–60%]).
Conclusions
RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.
8.Refractory Diarrhea Associated with Carcinoid Syndrome Improved after Opioid Switching from Fentanyl to Morphine
Madoka ITO ; Ryo MATSUNUMA ; Haruka HARANO ; Junichi TASAKI ; Takashi YAMAGUCHI
Palliative Care Research 2023;18(3):171-176
Background: In the case of refractory diarrhea that cannot be treated with loperamide only, drugs such as octreotide and serotonin receptor antagonists are generally recommended. We have reported a case of refractory diarrhea associated with carcinoid syndrome in which symptoms improved only with opioid switching, without octreotide. Case: We experienced a case of a 28-year-old female with cervical cancer. She was diagnosed with recurrence after cervical cancer surgery and presented with pain and diarrhea. Her diarrhea did not improve sufficiently after taking loperamide. She was admitted to the palliative care hospital for symptom control due to persistent diarrhea and right lower extremity pain associated with bone metastasis. We diagnosed the cause of her diarrhea as carcinoid syndrome by some laboratory examination. For pain management, we switched opioids from transdermal fentanyl to continuous subcutaneous infusion of morphine. It resulted in pain relief and improvement in the frequency of diarrhea, and she was able to be discharged home. Conclusion: In cases of refractory diarrhea and in patients who need opioids, there is one option to use morphine. If it is effective, it may simply resolve both pain and diarrhea and reduce the use of multiple medications.
9.The Effect of Fan Therapy for Dyspnea in Patients with Chronic Progressive Disease: Systematic Review and Meta-analysis
Jun KAKO ; Yoichi NAKAMURA ; Tomohiro NISHI ; Yusuke TAKAGI ; Yoshinobu MATSUDA ; Hiroaki WATANABE ; Yoko KASAHARA ; Sho GOYA ; Hiroyuki KOHARA ; Masanori MORI ; Takashi YAMAGUCHI
Palliative Care Research 2022;17(1):33-42
Objective: To evaluate the efficacy of fan therapy for the relief of dyspnea in patients with chronic progressive disease. Methods: A systematic electronic database search of all available articles published before October 23, 2019 was conducted using Ichushi-Web of the Japan Medical Abstract Society databases, CENTRAL, EMBASE, and MEDLINE. In addition, a hand-search for updates was performed using PubMed on June 30, 2020 and December 7, 2021. The inclusion criteria were: 1) any RCTs comparing the effect of fan therapy with any other intervention, and 2) patients aged ≥18 years. Exclusion criteria were: 1) duplicate references, and 2) conference presentations. Results: We identified 110 studies, of which 10 met our criteria for inclusion. Finally, five studies were used in the meta-analysis. Fan therapy significantly improved dyspnea in patients with chronic progressive disease compared to control groups with a standardized mean difference of −1.43 (95% confidence interval: −2.70 to −0.17, I2=94%, p<0.0001). Conclusion: Fan therapy was found to be effective in reducing dyspnea in chronic progressive disease.
10.Investigation of the Differences between Clinical Trial Exclusion Criteria and Contraindications at the Time of Marketing of Monoclonal Antibody Drugs
Hideki ARIMA ; Fumiya OCHI ; Kyoji KOUDA ; Takashi KITAHARA
Japanese Journal of Drug Informatics 2022;24(2):98-104
Objective: In clinical settings, new drugs are frequently administered to patients who have been excluded in the clinical trials. However, health professionals seldom recognize this. Focusing on monoclonal antibody drugs, we conducted a questionnaire survey of pharmaceutical companies and accumulated cases in which risk management differed between clinical trials and post-marketing.Methods: We obtained information on exclusion criteria for clinical trials of monoclonal antibody preparations from pharmaceutical companies. We compared these exclusion criteria with the contraindicated items in the package insert.Results: The most common exclusion criteria were “reproductive-related events”, “cancer-related events”, “HBV/HCV infection”,and “history of allergy/hypersensitivity”. The most common contraindications in the package insert were “history of allergy/hypersensitivity”, “other infectious diseases”, and “tuberculosis infection”. The average number of exclusion criteria for safety measures at the time of clinical trial was 10.1per drug, while that of contraindications was 2.1per drug; the difference was statistically significant. In addition, there were significant differences in one clinical trial exclusion criterion ( “upper age limit” ) and two contraindications ( “tuberculosis infection” and “other infectious diseases” ) between antineoplastic agents compared to therapeutic agents for autoimmune-related diseases. In half the products, serious adverse drug reactions related to the exclusion criteria that were not contraindicated were reported after marketing.Conclusion: Because the contraindications at the time of marketing are drastically fewer compared to the exclusion criteria at the time of clinical trials, pharmacists should inform doctors of it and carefully monitor the outcomes of new drugs that have not been used with patients with complications.


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