Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Probable effects of polypharmacy and equivalent doses of psychotropic drugs on prevalence of adverse drug events among psychiatric inpatients in a general hospital in Japan.

OBJECTIVE: In psychiatry, polypharmacy or high psychotropic drug doses increase adverse drug event (ADE) prevalence. However, the full relationship between polypharmacy and ADEs is unclear, and few studies have evaluated dose equivalents for psychotropic drugs for ADEs. Thus, we conducted a retrospective analysis to clarify the effects of polypharmacy and chlorpromazine (CP)-, diazepam (DAP)-, and imipramine- equivalent doses on all ADEs in inpatients. METHODS: Psychiatric inpatients in a Japanese hospital from April 1, 2016 to March 31, 2018, were enrolled. ADE severity and causality were assessed. Multiple logistic regression analyses were performed to evaluate ADE risk factors. RESULTS: Among 462 patients analyzed, out of 471 patients enrolled, 145 (31.4%) experienced ADEs. The causality assessment determined that "possible" was 96.5%. The most common ADEs were nervous system disorders (35%). Multiple logistic regression analyses indicated an increase in ADE prevalence with the number of drugs used (≥5; p = 0.026); CP-equivalent dose (p = 0.048); and endocrine, nutritional, and metabolic disorders (p = 0.045). DAP-equivalent dose; infectious and parasitic diseases; and injury, poisoning, and consequences of other external causes decreased ADE prevalence (p = 0.047, 0.022, and 0.021, respectively). CONCLUSIONS: Avoiding polypharmacy in psychiatric inpatients and adjusting drug regimens to safe equivalent doses could reduce ADEs during hospitalization.

[Effectiveness of Pharmaceutical Intervention While Administering 5-Aminolevulinic Acid Hydrochloride through a Collaboration of Physicians and Pharmacists].

5-aminolevulinic acid hydrochloride is a highly effective drug in reducing tumor residuals in transurethral resection of the bladder tumors; however, hypotension is a serious side effect that causes clinical problems. To avoid serious side effects, a pharmacist, in consultation with a physician, decided to discontinue the antihypertensive medication, and the effect of this pharmaceutical intervention was examined retrospectively. This study included patients who received 5-aminolevulinic acid hydrochloride at Gifu Municipal Hospital and were instructed to continue receiving their usual antihypertensive medication on the day of surgery. The control group comprised 17 patients before the pharmaceutical intervention, and the intervention group comprised 18 patients after the pharmaceutical intervention. The difference in systolic blood pressure before and after 5-aminolevulinic acid hydrochloride administration was -19.4±22.5 mmHg in the control group and -2.8±16.0 mmHg in the intervention group. The intervention group showed a significantly lower decrease in blood pressure(p=0.019). Intervention to avoid hypotension through the collaboration between physicians and pharmacists may be effective in improving the safety of 5-aminolevulinic acid hydrochloride.

Melphalan Febrile Neutropenia Risk Factors.

This study aimed to identify the risk factors of febrile neutropenia(FN)onset associated with melphalan(L-PAM)therapy. Thirty-nine patients(21 men, 18 women)were administered L-PAM intravenously for multiple myeloma(MM)from April 2011 to February 2022 at the Department of Hematology of Gifu Municipal Hospital. Patients were classified into those with and without FN(Grade 3 or higher), complete blood count and liver function tests were performed immediately before starting therapy. Univariate analysis with Fisher's exact probability test was performed. Factors with p<0.2 were considered as independent variables for multivariate analysis in the multiple logistic regression analysis. A multivariate analysis with 2 independent variables, lactate dehydrogenase(LD)level>222 U/L(upper limit of the facility reference value)and white <3.3×103/µL(lower limit of the facility reference value)from the univariate analysis, and FN onset(Grade 3 or higher)as the dependent variable showed that LD level>222 U/L(odds ratio: 6.33, 95% confidence interval: 1.12-35.8, p=0.037)was a significant factor. In conclusion, patients with LD levels >222 U/L immediately before starting therapy require adequate monitoring for FN onset following L-PAM administration.

[Predictors of Nivolumab-Induced Skin Reactions].

Skin reactions to nivolumab are typical immune-related adverse events. We investigated the relation between patient background and test values before nivolumab administration and skin reactions. From February 2016 to February 2017, we evaluated the clinical outcomes of 21 patients who were administered nivolumab. Patients were divided into 2 groups: 3 cases of skin reactions to nivolumab(skin reaction group)and 18 cases without skin reactions to nivolumab(non-skin reaction group). In the skin reaction group, the numbers of eosinophils and basophils before nivolumab administration were significantly higher than those in the non-skin reaction group(p=0.0015 and p=0.0075, respectively). It was suggested that the numbers of eosinophils or basophils before nivolumab administration might be associated with the appearance of skin reactions.

Impact of pharmacist counseling on reducing instances of adverse events that can affect the quality of life of chemotherapy outpatients with breast Cancer.

BACKGROUND: In recent years, cancer chemotherapy is being conducted at outpatient clinics, wherein pharmacists are involved with patient guidance and management of adverse events as experts in medication therapy. Therefore, we clarified the influence of interventions by pharmacists during counseling of patients with cancer on patients' quality of life. METHODS: To determine this influence, we conducted a survey to assess the quality of life of 39 patients with breast cancer who underwent their initial course of outpatient cancer chemotherapy at Gifu Municipal Hospital. A quality of life survey was conducted before the 1st, 2nd, and 3rd courses of treatment and was based on a method obtained from a survey paper entitled, "Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs." RESULTS: Twenty patients were assigned to the intervention group, which received pharmacist counseling, and nineteen patients were assigned to the non-intervention group, which received no pharmacist counseling. Both groups were compared immediately before the 1st course and 2nd course. Regarding the subscale of social relationships, a significant difference was observed for malaise (p = 0.043), with the non-intervention group experiencing them to a greater degree than the intervention group. Regarding the change between immediately before the 1st course and the 3rd course, a significant difference was observed in the subscale of social relationships for nausea (p = 0.017), with the non-intervention group experiencing it to a greater degree than the intervention group. CONCLUSIONS: The results suggest that receiving pharmacists' guidance on adverse events and individually adjusted prescriptions tailored to address the occurrence of adverse events improved the treatment environment and enhanced the quality of life in the intervention group. These findings are beneficial in maintaining patients' quality of life during cancer treatment. TRIAL REGISTRATION: No. UMIN000027171, Registration date: Apr 27, 2017. Retrospectively registered.

An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life.

OBJECTIVE: To examine how clinical and demographic patient baseline characteristics influence effectiveness of duloxetine versus selective serotonin reuptake inhibitor (SSRI) treatment, in real-world Japanese clinical settings of patients with major depressive disorder (MDD) and associated painful physical symptoms (PPS). METHODS: This was a multicenter, 12-week, prospective, observational study in patients with MDD (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate PPS (Brief Pain Inventory-Short Form [BPI-SF] average pain ≥3). Patients received duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine). Assessments were made by using BPI-SF average pain, 17-item Hamilton Rating Scale for Depression (HAM-D17), EuroQol 5-dimension questionnaire, Social Adaptation Self-Evaluation Scale, Global Assessment of Functioning, and ability to work. Predefined subgroups included the number of previous episodes of depression (0 vs ≥1), baseline BPI-SF average pain score (≤6 vs >6), baseline HAM-D17 total score (≤18 vs >18), baseline HAM-D17 retardation (≤7 vs >7) and anxiety somatic subscale scores (≤6 vs >6), and age (<65 vs ≥65 years). RESULTS: Treatment effectiveness was evaluated in 523 patients (duloxetine N=273, SSRIs N=250). Treatment with duloxetine was superior to SSRIs on most outcome measures in patients experiencing their first depressive episode, those with higher baseline PPS levels, and in patients with more severe baseline depression. This was also the case for older patients. In patients with less severe depression, SSRI treatment tended to show more improvements in depression and quality of life measures versus duloxetine treatment. CONCLUSION: These preplanned subgroup analyses of data from a prospective observational study suggest that, for Japanese MDD patients with PPS, duloxetine is more effective than SSRIs in patients with a first episode of MDD, with more severe depression, or more severe PPS.

An observational study of duloxetine versus SSRI monotherapy for the treatment of painful physical symptoms in Japanese patients with major depressive disorder: primary analysis.

OBJECTIVE: The objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI) monotherapy, in the treatment of painful physical symptoms (PPS) in Japanese patients with major depressive disorder (MDD) in real-world clinical settings. METHODS: This was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF) average pain score (item 5) ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine) for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline. RESULTS: A total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250). The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine, -2.8 [-3.1, -2.6]; SSRIs, -2.5 [-2.8, -2.3]; P=0.166). There was a numerical advantage for duloxetine in improvement from 4 to 12 weeks post-baseline, and the difference was statistically significant at 8 weeks post-baseline (least-squares mean change from baseline [95% confidence interval]: duloxetine, -3.6 [-3.9, -3.3]; SSRIs, -3.1 [-3.4, -2.8]; P=0.023). The 30% and 50% responder rates were significantly higher in patients treated with duloxetine at 4 and 8 weeks post-baseline. There were no serious adverse events experienced by duloxetine-treated patients. The rate of discontinuations due to adverse events was similar for duloxetine and the SSRIs (1.0% and 0.8% of patients, respectively). CONCLUSION: In this observational study, BPI-SF improvement was not significantly different at 4 weeks, the primary endpoint; however, patients treated with duloxetine tended to show better improvement in PPS compared to those treated with SSRIs.

The impact of side effects from outpatient chemotherapy on presenteeism in breast cancer patients: a prospective analysis.

In the field of occupational health services, productivity loss can be expressed by absenteeism (i.e., employees being absent from work and taking leave due to health problems) and presenteeism (i.e., a reduction in the ability to perform one's tasks at work). Similar to absenteeism, it is important to assess presenteeism because it can severely reduce productivity. Despite numerous reports about the impact of disease and medical treatments on presenteeism, there is a lack of data regarding the influence of medication side effects. In this study, a prospective analysis was conducted via questionnaire survey to clarify the influence of the side effects of anticancer drugs on presenteeism in workers receiving outpatient chemotherapy for breast cancer. Between December 2012 and November 2013, the influence of side effects on the quality of life, absenteeism, and presenteeism was investigated via a questionnaire conducted before and after 1 course of chemotherapy in 19 currently employed breast cancer patients receiving outpatient chemotherapy for the first time at Gifu Municipal Hospital, Japan. The rate of absenteeism was 24.7 %, resulting in financial losses of 2002 yen/day (national statistical data) and 881 yen/day (our questionnaire data). The rate of presenteeism was 33.7 %, resulting in financial losses of 1354 yen/day (national statistical data) and 1263 yen/day (our questionnaire data). Furthermore, a significant positive correlation was observed between absenteeism and presenteeism (r = 0.687, p = 0.001), suggesting that the productivity losses associated with presenteeism due to the side effects of anticancer drugs in breast cancer patients are large and similar to that associated with absenteeism in these patients. Our results may be useful for improving the occupational health of workers receiving chemotherapy for cancer.

The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients.

The objective of our study was to clarify the impact of adverse events associated with the initial course of outpatient chemotherapy on the quality of life of breast cancer patients. We conducted a survey to assess the quality of life in 48 breast cancer patients before and after receiving their first course of outpatient chemotherapy at Gifu Municipal Hospital. Patients completed the European Quality of Life 5 Dimensions and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs before and after 1 course of outpatient chemotherapy. European Quality of Life 5 Dimensions utility value and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score decreased significantly after chemotherapy (p<0.001 and p = 0.018, respectively). The mean scores for the activity, physical condition, and psychological condition subscales of the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs decreased significantly after chemotherapy (p = 0.003, p<0.001, and p = 0.032, respectively), whereas the social relationships score increased significantly (p<0.001). Furthermore, in the evaluation of quality of life according to individual adverse events, the decrease in quality of life after chemotherapy in terms of the European Quality of Life 5 Dimensions utility value and the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score was greater in anorexic patients than in non-anorexic patients (p = 0.009 and p<0.001, respectively). This suggests that anorexia greatly reduces quality of life. Our findings reveal that anticancer drug-related adverse events, particularly anorexia, reduce overall quality of life following the first course of outpatient chemotherapy in current breast cancer patients. These findings are extremely useful and important in understanding the impact of anticancer drug-related adverse events on quality of life.

Economic evaluation of adjustments of levofloxacin dosage by dispensing pharmacists for patients with renal dysfunction.

Since April 2011, a dosage adjustment program has been implemented at Gifu Municipal Hospital. In this program, upon receiving a prescription for renally eliminated drugs, pharmacists verify patients' serum creatinine concentrations by using a computerized medical record system to evaluate the patient's kidney function and suggest the appropriate dosage to doctors, if necessary. In our study, we used questionnaires that were administered to pharmacists and doctors at the hospital to investigate their respective working times and the cost of the program, in order to comprehensively analyze the clinical resource costs of the hospital and evaluate the economic burden of the program for levofloxacin. In addition, we studied the pharmacists' and doctors' attitudes toward the program and the circumstances of prescriptions for patients with renal dysfunction. The questionnaire comprised items such as time required for the program; attitude toward the program, including satisfaction; and attitude toward the circumstances of prescriptions for patients with renal dysfunction. The pharmacists' and doctors' working times and cost of the program were obtained from the questionnaire responses. For cost estimation, we used data from this study as well as those of our previous study that suggested that the levofloxacin program was economically beneficial. Furthermore, their attitudes toward the program and circumstances of prescriptions for patients with renal dysfunction were clarified. Regarding the pharmacists' tasks and interventions, we need to not only investigate attitudes toward them but also perform a cost analysis by the method of the economic evaluation of the medical techniques used in our study.

Decreased levels of ghrelin, cortisol, and fasting blood sugar, but not n-octanoylated ghrelin, in Japanese schizophrenic inpatients treated with olanzapine.

The mechanism by which chronic administration of olanzapine induces a marked weight gain in patients with schizophrenia remains unknown. We examined the influence of long-term treatment with olanzapine on plasma levels of hormones regulating food intake and energy homeostasis in schizophrenia. In this study, olanzapine was administered to 28 Japanese inpatients for 16 weeks after switching from typical antipsychotic drugs or risperidone. At endpoint, no significant changes in body weight or body mass index were found. There was a significant decrease in the plasma levels of ghrelin without any accompanying change in active, n-octanoylated ghrelin. Serum levels of leptin tended to be increased and a significant reduction in plasma cortisol levels was found. In addition, the levels of fasting blood sugar as well as free fatty acid were significantly decreased. Furthermore, we did not confirm any marked weight gain induced by chronic administration of olanzapine as previously reported. The reason for this discrepancy may be due to differences in subjects and treatment settings. Based on these findings, it is unlikely that the decrease in plasma ghrelin levels by chronic administration of olanzapine affects weight gain. Further studies examining the effect of chronic olanzapine administration on weight and energy homeostasis in inpatients are required.

Influence of immobilization stress on the expression and phosphatase activity of protein phosphatase 2A in the rat brain.

BACKGROUND: Protein phosphatase 2A (PP2A) is a major kinase phosphatase that plays an important role in regulating the activities of protein kinase cascades. It has been revealed that stress changes neuronal gene expression by activating these cascades. We examined the expression of the catalytic subunit C and serine and threonine phosphatase activity of PP2A in the rat frontal cortex and hippocampus following various immobilization stress paradigms. METHODS: Immunoblot and immunohistochemical analyses were performed to examine the expression of PP2A. The level of phosphatase activity of PP2A was determined as the amount of free phosphate generated from a synthetic phosphopeptide. RESULTS: Immunoblot analysis revealed no significant change in the level of PP2A immunoreactivity in response to either a single or repeated stress. Immunohistochemical analysis revealed that neither a single nor repeated stress changed PP2A immunoreactivity in the hippocampus; however, the levels of serine and threonine phosphatase activity in the frontal cortex and hippocampus were significantly upregulated in response to a single or repeated stress. CONCLUSIONS: These results demonstrated that both a single and repeated immobilization stress upregulated the activity of PP2A in the rat brain, suggesting that PP2A may be involved, at least in part, in the downregulation of protein kinase activation induced by stress.

Imipramine, but not lithium, induces the serine/threonine phosphatase activity of calcineurin without affecting its mRNA expression in the rat brain.

The influence of imipramine and lithium on the expression of calcineurin (CaN) and its serine/threonine phosphatase activity in the rat frontal cortex and hippocampus was examined. Northern blot analysis demonstrated that single or repeated (14 day) administration of imipramine did not affect the levels of CaN A (catalytic subunit) mRNA in rat brain. Similarly, the administration of lithium for 1 or 14 days had no effect on the expression of CaN A mRNA. In contrast, the acute administration of imipramine significantly increased CaN activity in the cortex and hippocampus. In addition, the chronic (14 day) administration also significantly increased CaN activity. However, administration of lithium for either 1 or 14 days did not influence CaN activity. These findings indicate that imipramine, but not lithium, increases the phosphatase activity of CaN, suggesting that the changes in neuronal functions induced by CaN may be involved in the molecular activity of imipramine.