Relationship between Pain Scores and EORTC QLQ-C15-PAL Scores in Outpatients with Cancer Pain Receiving Opioid Therapy.

Cancer pain is one of the most frequent and distressing symptoms associated with cancer and has a serious impact on the QOL of patients. However, inadequate pain treatment has also been reported in outpatients with cancer pain. The aims of this study were (1) to evaluate the relationship between pain intensity using the Numerical Rating Scale (NRS) and QOL scores using the Japanese version of the European Organization for Research and Treatment of Cancer (QOL Questionnaire Core 15 for Palliative Care (QLQ-C15-PAL)), and (2) to investigate their association with various pain patterns, especially with baseline and breakthrough pain. Forty outpatients who were receiving opioid therapy and obtained informed consent participated. We collected a total of 222 pharmacist consultations during the study period. Global QOL scores and pain scores (PA) in the QLQ-C15-PAL (PA score, 0-100) at the first visit were significantly correlated with worst pain intensity. In addition, the scores for the worst pain were significantly correlated with not only physical functioning scores but also with emotional functioning scores. The correlations between the worst pain NRS and PA scores were positive. Specifically, patients tended to report large variability of NRS scores when the PA score was less than 40 and also when they exhibited pain patterns with "baseline and breakthrough cancer pain in the same day" or "baseline pain throughout the day." Reducing the worst pain NRS and relieving breakthrough pain appear to be important measures to improve the QOL of outpatients receiving opioid therapy for cancer pain.

Effect of Continuous Pharmacist Interventions on Pain Control and Side Effect Management in Outpatients with Cancer Receiving Opioid Treatments.

For improving the QOL of patients diagnosed with cancer, early palliative care is recommended, aiming to minimize pain and opioid-induced side effects. Herein, we evaluated the effect of continuous interventions for pain management and opioid-induced side effects in outpatients with cancer. Pharmacists continuously performed interventions on patients on their hospital visits, starting from the first visit for opioid introduction to intervention via telephone. We recorded their pain patterns and intensities, use of rescue doses, and types and degrees of side effects during these interventions. The physicians were suggested appropriate recommendations for increased doses or alternative opioids when the pharmacists considered the analgesic dose should be titrated. During the study period, palliative care pharmacists conducted 105 interviews for 27 patients (male: 19 and female: 8) with cancer pain. Pain intensities significantly decreased after the pharmacists' continuous intervention, including those from telephone interviews, with their appropriate recommendations and increased opioid doses. Side effects such as nausea and constipation increased or remained unaffected even after the intervention, likely due to the increased opioid doses. Approximately 90% of recommendations for pain control were accepted by the physicians and helped to control the pain intensities. Before starting physician consultations, pharmacists informed the patients that adequate pain control and side effect management were achievable through regular interviews, wherein patient symptoms were monitored and patients received detailed explanations of pharmaceutical care and courteous and continuous counseling.

Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.

The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.

Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. METHODS: We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. RESULTS: Pearson correlation analysis showed that EPA (R = 0.25, P <0.01), EPA/AA ratio (R = 0.22, P = 0.01), and left ventricular ejection fraction (R = 0.15, P = 0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded. CONCLUSIONS: Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation potentially lends further support to a role of dietary n-3 PUFAs in preventing the cognitive decline in CAD patients.

Pulmonary Arterial Hypertension in Neurofibromatosis Type 1: A Case with a Novel NF1 Gene Mutation.

Neurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.

Perspectives of Japanese mothers with severe mental illness regarding the disclosure of their mental health status to their children.

This study examined Japanese mothers with severe mental illness and their perspectives about disclosing their mental health status to their children. Seventy-four outpatients diagnosed with schizophrenia or mood disorders were recruited. We utilized a cross-sectional design and a self-report questionnaire. Approximately 72% of the participants disclosed their mental health status to their children. The reasons for disclosure and nondisclosure varied. Our findings indicate that although both the disclosing and nondisclosing groups held beliefs about disclosure, many mothers appeared to struggle with these issues. It is essential that clinicians are aware of this issue so they may appropriately help the mothers.

Regression of left ventricular hypertrophy after tafamidis therapy in a patient with transthyretin amyloidosis variant.

Transthyretin amyloidosis (ATTR) variant is a life-threatening hereditary disease predominantly affecting the peripheral nervous system and heart. Tafamidis, which prevents the deposition of amyloid by stabilizing transthyretin, is available for the treatment of neuropathy and cardiomyopathy of ATTR. However, whether tafamidis could eliminate established amyloid deposits and improve cardiac function remains unknown. We reported a case of regression of left ventricular hypertrophy after tafamidis therapy in a patient with an ATTR variant. J. Med. Invest. 69 : 320-322, August, 2022.

Relationship between positive self-recognition of maternal role and psychosocial factors in Japanese mothers with severe mental illness.

Mothers with mental illness have positive self-recognition of maternal role (PM), and it is important for parenting. The purpose of this study was to determine the psychosocial factors related to the PM. We recruited a total of 74 women diagnosed as having schizophrenia or mood disorders according to the DSM-IV-TR and who had minor children. Participant completed devaluation-discrimination measure, The social support questionnaire, self-efficacy for community life scale (SECL), parenting stress-short form scale (PS-SF), and Acceptance of maternal role scale. To identify factors predicting the PM, we utilized hierarchical regression analysis. The variables in all blocks explained 53% of the variance in the PM. In the final model, 'hard' living conditions (ß = -0.31, P < 0.05), SECL (ß = 0.34, P < 0.01) and PS-SF (ß = -0.45, P < 0.01) were significant predictors of the PM. Our result indicates that psychosocial approach could enhance the PM.

Safety and Effectiveness of Letermovir in Allogenic Hematopoietic Stem Cell Transplantation Recipients: Interim Report of Post-marketing Surveillance in Japan.

OBJECTIVE: Since May 2018, a 6-year post­marketing surveillance (PMS) has been underway to evaluate the safety and effectiveness of letermovir for cytomegalovirus (CMV) prophylaxis in Japanese patients with allogenic hematopoietic stem-cell transplantation (allo-HSCT). The interim PMS data for 461 patients collected as of March 2021 are reported in this publication. METHODS: The case report forms (CRFs) were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) using data elements in the Transplant Registry Unified Management Program (TRUMP) and sent to individual HSCT centers to decrease burden of reporting. These CRFs were completed by physicians in the respective HSCT centers and sent to MSD K.K., Tokyo, Japan. RESULTS: Allo-HSCT recipients prescribed with letermovir for CMV prophylaxis were included across 136 centers in Japan between May 2018 and March 2021. Safety and effectiveness were assessed for 460 and 373 patients, respectively. Of the patients in the safety analysis, 13.9 % experienced adverse drug reactions, the most frequent of which were renal impairment (2.2 %) and nausea (1.7 %). Among patients in the effectiveness analysis, the overall CMV antigen positivity rate was 21.2 % at Week 14 and 37.5 % at Week 24 after allo-HSCT. CONCLUSIONS: Interim data from this largest of real-world studies confirm the safety and effectiveness of letermovir for CMV prophylaxis in Japanese allo-HSCT recipients. Given the limited data on Asian patients for letermovir use, this survey will provide valuable information for medical decision-making in routine clinical practice, serving as a vital supplement to the results obtained from clinical trials.

Healthcare resource utilization and economic burden of antifungal management in patients with hematologic malignancy in Japan: a retrospective database study.

OBJECTIVE: To examine treatment patterns of real-world antifungal management of patients at high risk of invasive fungal infections (IFI) and evaluate healthcare resource utilization and costs associated with antifungal management of IFIs in Japan. METHODS: This retrospective, observational study extracted data from a hospital-based claims database for patients in Japan who either (a) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), or (b) were hospitalized with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and received chemotherapy during the study period of January 2010 to January 2019. RESULTS: 863 patients were included in the allo-HSCT cohort and 4498 patients were included in the AML/MDS cohort. In the allo-HSCT cohort, 91% received more than one antifungal drug during the index hospitalization. In the AML/MDS cohort, approximately 50% received more than one antifungal drug during the index hospitalization. For both the allo-HSCT and AML/MDS cohorts, about 90% of the total cost was attributed to inpatient costs. Of note, both the total cost (the total inpatient and outpatient cost) and the index hospitalization costs were higher in patients treated with multiple antifungal drugs than in those treated with a single antifungal drug during the index hospitalization. Despite being at high IFI risk, 12% of the patients in the AML/MDS cohort did not receive antifungal drugs during the index hospitalization. CONCLUSIONS: Most patients with hematologic malignancy and high IFI risk underwent complicated antifungal management requiring use of multiple drugs, and accounted for high healthcare resource utilization and costs.

The disease burden of mucormycosis in Japan: results from a systematic literature review and retrospective database study.

OBJECTIVE: To evaluate outcomes, healthcare resource utilization, and costs associated with mucormycosis in inpatient settings in Japan. METHODS: We performed a systematic literature review, followed by a retrospective database study using hospital health claims for patients in Japan hospitalized with a diagnosis of mucormycosis between January 2010 and January 2019. Outcomes assessed included duration of index hospitalization; index stay mortality; hospital readmission within 30, 60, and 90 days after index hospitalization discharge; drug/treatment utilization and patterns; number of patients examined for mucormycosis during the index hospitalization; and index stay inpatient costs. RESULTS: From our systematic literature review of articles describing 133 patients with mucormycosis, mortality in the index hospitalization was 55.6%. From our database study of 126 patients hospitalized for mucormycosis, mortality during the index hospitalization was 35.7% and mean index stay duration was 94 days. Hematologic malignancies were the most common risk factor in the literature review and the most common comorbidity in the database study. During the index stay, 39 patients (31.0%) received liposomal amphotericin B (L-AMB) treatment and 74 patients (58.7%) received other antifungal treatments. Median total inpatient costs for the index hospitalization were equivalent to approximately US$60,945, including US$29,283 in drug costs. CONCLUSIONS: This study investigated the healthcare resource utilization and cost of medical resources caused by mucormycosis in Japan. The drug costs for antifungal treatments comprised about half of total inpatient costs. Mucormycosis leads to high mortality, high healthcare resource utilization, and high costs.

Effects of Culture Conditions (Microplate and Solvent) on in vitro Antifungal Activity of Caspofungin Against Candida Species.

Effects of the type of microplates and solvent for preparation of caspofungin (CPFG) on antifungal susceptibility testing of CPFG against clinical isolates of Candida albicans, Candida glabrata, and Candida krusei (20 strains each) by broth microdilution method according to the Clinical and Laboratory Standards Institute were evaluated. When CPFG was dissolved in water, MICs against the three Candida species decreased 3.1-6.0-fold in surface-untreated microplates compared to those in treated microplates. When CPFG was dissolved in dimethyl sulfoxide, MICs against the three Candida species decreased 1.3-2.5-fold in surface-untreated microplates compared to those in treated microplates. Differences in MICs according to the type of solvent did not exceed the difference for one dilution interval (0.5-2-fold MIC ratio) regardless of whether the microplate surface was treated or not. These findings suggest that differences in CPFG MICs may depend mainly on the type of surface treatment of assay microplates.

The clinical and economic burden of cytomegalovirus management post allogeneic hematopoietic stem cell transplantation in Japan - a retrospective database study.

Introduction: Reactivation of cytomegalovirus (CMV) infection is a major threat and it causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There remains, however, a paucity of evidence regarding the economic burden of current CMV management in Japan. The aim of this study is to characterize the healthcare resource utilization (HCRU) and cost incurred for CMV management post allo-HSCT, using a Japanese hospital claims database.Methods: Patients who underwent allo-HSCT between April 2010 and March 2018 were identified and followed up for 180 days.Results: In total, 916 patients were included for analysis and categorized into CMV (-) group and CMV (+) group based on the presence of a CMV episode within 100 days post allo-HSCT. A CMV episode was defined as evidence of receiving at least one dose of the following anti-CMV drugs, ganciclovir, foscarnet, or valganciclovir. The mean (± standard deviation [SD]) total length of stay was 93.6 (± 43.7) days in the CMV (+) group, which was significantly longer than 55.9 (±40.6) days in the CMV (-) group, and this trend was more pronounced in patients with multiple CMV episodes. The mean (±SD) total medical cost within 180 days post allo-HSCT was US$122,328 (±56,977) in the CMV (+) group, while the mean total medical cost was US$75,344 (±43,821) in the CMV (-) group. Moreover, transfusion and antimicrobial use was observed as the major medication cost component, which is suggestive of the indirect effect of CMV episodes.Conclusion: This study demonstrated that CMV episodes post allo-HSCT were associated with increased HCRU and cost.

Lambda-like J wave due to acute myocardial infarction of the diagonal branch.

The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019.

Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome.

AIM: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited. METHODS: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography. RESULTS: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR. CONCLUSION: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

Narratives by Japanese mothers with chronic mental illness in the Tokyo metropolitan area: their feelings toward their children and perceptions of their children's feelings.

Women with mental illness generally have normal fertility rates. Mothers with mental illness think that their children are important for their lives but also experience difficulties in relating to their children. Therefore, it is important to understand the mothers' perception of what experiences influence them or their parenting practices in relationships with their children. We conducted narrative interviews with 20 Japanese mothers who were being treated for either schizophrenia or mood disorders. The data were analyzed using the Modified Grounded Theory Approach. For the mothers, their feelings toward their children and their perception of their children's feelings toward them or their illness influenced the mothers and their parenting practices. Implications for support are discussed and directions for future research are presented.

Edoxaban improves acute venous thromboembolism while preserving protein C and protein S levels.

BACKGROUND: It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. METHODS AND RESULTS: We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting. Before treatment and 2 weeks after treatment, we evaluated thrombotic burden using ultrasound or computed tomography angiography. We also evaluated thrombin generation, represented by prothrombin fragment F1+2; thrombus degradation, represented by D-dimer; and levels of anticoagulants, including protein C, protein S, and antithrombin III. Both edoxaban and warfarin treatment improved thrombotic burden and decreased prothrombin fragment F1+2, and D-dimer. Edoxaban treatment preserved protein C and protein S levels. In contrast, warfarin decreased protein C and protein S levels. Neither treatment affected antithrombin III. CONCLUSIONS: Edoxaban improves VTE while preserving protein C and protein S levels, thereby indicating that edoxaban improves thrombotic burden while maintaining levels of anticoagulants.