The Relationship Between Dialysis Patients' Quality of Life and Caregivers' Quality of Life.

Patients on dialysis require caregiving and assistance in their daily lives from family members and/or others for hospital visitation and supervised administration. This places a considerable burden on caregivers, which can in turn influence caregivers' quality of life (QOL). We recruited dialysis patients and their caregivers to elucidate how the QOL of patients relates to that of their caregivers'. Patients completed the EuroQol 5-Dimension scale (EQ-5D) and Kidney Disease Quality of Life-Short Form. Caregivers completed the EQ-5D and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We calculated utility index values for the EQ-5D, and physical, mental (MCS), and role-social component summary scores for the SF-36. Compared to national norms, the caregivers of dialysis patients tended to have poor physical health-related QOL but normal mental health-related QOL, as also found with patients. The multivariate analysis revealed that ≥ median dialysis period and ≥ average burden of kidney disease were significantly related to caregiver MCS score (odds ratios; 6.79 and 9.89, respectively). Caregivers tended to have lower physical health-related QOL if their patients had high social QOL, and lower mental health-related QOL during the early stage of the patient's dialysis treatment, and when patients experienced low disease-targeted QOL.

The Effect of Quality of Life on Medication Compliance Among Dialysis Patients.

Dialysis treatment is known to lead to reduced quality of life (QOL) among patients. This decreased QOL is believed to influence medication compliance, although this effect has not yet been clarified. In this study, we investigated whether decreased QOL due to dialysis treatment does in fact influence medication compliance. Participants were 92 patients who self-managed their medication and were receiving dialysis treatment at Secomedic Hospital or Chiba Central Medical Center. We surveyed their age, sex, dialysis period, and medication management situation, and administered the EQ-5D and Kidney Disease Quality of Life Instrument-Short Form. A multiple logistic regression analysis with medication compliance as the dependent variable and QOL as the independent variable was conducted. The recovery rate and effective response rate were both 100%. The results indicated that patients with good sleep QOL (mean or above) had higher odds of medication compliance (odds ratio, 3.36; 95% confidence interval, 1.26-8.96; P = 0.016). Therefore, improving the quality of sleep of dialysis patients might help to improve their medication compliance.

Signals of gastroesophageal reflux disease caused by incretin-based drugs: a disproportionality analysis using the Japanese adverse drug event report database.

BACKGROUND: Incretin-based drugs are important in the treatment of type 2 diabetes. However, among the incretin-based drugs, glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have been reported to cause gastroesophageal reflux disease (GERD)-like symptoms making it difficult to continue treatment. Therefore, with the aim of clarifying the relationship between incretin-based drugs and GERD-like symptoms, we conducted a pharmacoepidemiological study using the Japanese adverse drug event report database (JADER). METHODS: Dipeptidyl peptidase-4 inhibitors (DPP-4-Is) and GLP-1-RAs were set as the incretin-based target drugs. The reporting odds ratio (ROR) and the information component (IC) was used for the detection of quantitative signals. Furthermore, we also compared the time to onset of GERD-like symptoms by log-rank test. RESULTS: GERD-like symptoms were reported in 36 GLP-1-RAs cases (ROR: 5.61, 95% confidence interval (95% CI): 3.95-7.96 and IC: 2.17, 95% CI: 1.66-2.67) and GLP-1-RAs were detected in the signal. In contrast, DPP-4-Is were not detected in the signal.There was no sex difference with regard to the expression time of GERD-like symptoms by GLP-1-RAs (log-rank test, p = 0.5381). However, the expression time of GERD-like symptoms from GLP-1-RAs was shorter in patients older than 70 years of age than that in those younger than 70 years of age (log-rank test, p < 0.0001). CONCLUSIONS: The administration of GLP-1-RA had a higher incidence of GERD-like symptoms earlier than the administration of DPP-4-Is. In this study, although we think that further investigation is necessary, and suggest that patients older than 70 years of age who have been administered GLP-1-RAs need earlier attention to address GERD-like symptoms than younger patients.

Analyses of non-benzodiazepine-induced adverse events and prognosis in elderly patients based on the Japanese adverse drug event report database.

BACKGROUND: The contents of the guidelines for the use of non-benzodiazepines (Z-drugs) differ slightly between THE JAPANESE SOCIETY OF SLEEP RESEARCH and THE JAPAN GERIATRIC SOCIETY, and the recommended directions are conflicting. Therefore, we analyzed the use of the Japanese Adverse Drug Event Report database (JADER) for identifying adverse events (AEs) caused by Z-drugs and clarifying their occurrence trend and prognosis. METHODS: The signal value for comparison was calculated by using the proportional reporting ratio (PRR) and chi-squared test (χ2) results of data of elderly and non-elderly patients. Among AEs for which signals were detected in the elderly, we determined that those with lower signal values for non-elderly patients that were half the signal value of the elderly should be used with particular caution in the elderly. We also compared the prognoses. RESULTS: The AEs with > 1 risk ratio (RR) in elderly and non-elderly patients were regarded as those that should be noted in the prognosis of AEs in elderly patients. Furthermore, 28 AEs were detected in elderly patients' signals. In this study, in addition to movement disorders such as "falls" and "bone fractures," identified by two academic societies, signal characteristics of the elderly were obtained for psychiatric disorders and eye disorders. CONCLUSIONS: There was no difference in prognosis, but these disorders could reduce the quality of life of patients. Therefore, we consider that in prescribing appropriate drug therapy for insomnia, attention should be paid to the occurrence of the AEs caused by the Z-drugs revealed by this study and the guidelines.

The adoption of generic drugs by a hospital: effects on drug dispensation among community pharmacies.

BACKGROUND: The objective of the current study is to elucidate the effect that the adoption of generic drugs by a large hospital has on the dispensation of generic drugs by community pharmacies. We evaluated the percentage of generic drugs dispensed by pharmacies and the cost of drugs dispensed before and after the adoption of generic drugs by a large hospital. METHODS: Participants comprised patients who were admitted to Gifu Municipal Hospital prior to its adoption of generic drugs (November 1, 2013 to November 14, 2013) and after its adoption (November 1, 2014 to November 14, 2014) and who utilized generic drugs dispensed by pharmacies. RESULTS: Results indicated that the pre-adoption dispensation rate of generic drugs by pharmacies was 48.3% (477/926 drugs), while the post-adoption rate was 57.7% (604/1046 drugs), indicating an increase of 9.4 points (P < 0.001). Furthermore, an investigation into the price paid for generic drugs as a percentage of the total price paid for all drugs indicated the following: the pre-adoption percentage was 23.5% (9756/41,461 yen), and the post-adoption percentage was 34.1% (19,221/56,438 yen), indicating an increase of 10.6 points (P < 0.001). CONCLUSIONS: The results of this study revealed that the adoption of generic drugs by a hospital may promote the use of generic drugs by pharmacies and lead to reduced medical costs as well.

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.

Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

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.

Renal function evaluation in patients with cancer who were scheduled to receive carboplatin or S-1.

BACKGROUND: Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney. Serum cystatin-C (sCys-C) is a GFR marker with little affected by body muscle mass volume. And GFR equations based on serum creatinine (eGFRcreat) and sCys-C (eGFRcys) were developed; however, accuracy of eGFRcys has not been elucidated fully among patients with cancer. Therefore, we analyzed the performance of GFR equations among patients with cancer whose GFR values were measured by inulin clearance (Cin). METHODS: Study design was a cross-sectional study. Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients. Correlation with Cin and slope of regression line were evaluated in eGFRcreat and eGFRcys. Single and multiple regression analyses were analyzed to identify associating factors with eGFRcreat/Cin or eGFRcys/Cin. RESULTS: Age, body weight, body mass index (BMI) and sCr were different between cancer patients and non-cancer patients, but sCys-C and Cin were consistent in 2 groups. The slope of the regression line for Cin vs. eGFRcys with zero intercept in cancer patients was 1.10 (95 % CI: 1.02-1.17), which was significantly different from 1.0. In multiple regression analysis revealed that BMI and urinary creatinine excretion were significantly associated with eGFRcreat/Cin, and cancer was only associating factor with eGFRcys/Cin. CONCLUSION: eGFRcys should not be used for evaluation of renal function in patients with cancer because it underestimates GFR.

[Effects of the combination of angiotensin receptor blockers and thiazide diuretics on laboratory values (levels of serum potassium, sodium, and uric acid)].

The combination of angiotensin receptor blockers (ARB) and a thiazide diuretic (hereafter, ARB/diuretic) is expected to improve patient adherence and increase the therapeutic effects because of the lower number of pills that require to be administered. In addition, an ARB/diuretic combination alleviates hypokalemia that frequently develops in patients receiving thiazide diuretics. In this study, we used electronic medical records to investigate the laboratory values (serum levels of potassium, sodium, and uric acid) of 194 ambulatory and hospitalized patients at the Gifu Municipal Hospital who received ARB/diuretic combination therapy for the first time between February 2010 and September 2012. According to the grade of classification of low serum potassium and sodium levels, the serum potassium level in one patient was grade 3 and the serum sodium level in two patients was grade 3 after the initiation of ARB/diuretic combination therapy. After administration of ARB/diuretic combination therapy, two patients received potassium supplements because their serum potassium levels decreased below the reference value. Similarly, one patient received a sodium supplement because of a decrease in the sodium level below the reference value. Uric acid level increased above the reference value after administration of the ARB/diuretic combination therapy in one patient; thus, this patient received antihyperuricemic agents. Therefore, pharmacists must carefully monitor the serum levels of potassium, sodium, and uric acid, particularly in the first six months after the initiation of ARB/diuretic combination therapy.

Influence of angiotensin II receptor blocker combination tablet prescription on drug number and cost.

OBJECTIVES: Combination therapy using an angiotensin II receptor blocker is expected to promote medication adherence and alleviate economic burden among patients by reducing the number of drugs taken, and thereby to lower associated medical costs. In the present retrospective study, we conducted a survey on the use of angiotensin II receptor blocker-containing combination tablets as anti-hypertensive drugs, in particular angiotensin II receptor blocker/diuretic and angiotensin II receptor blocker/calcium channel blocker combinations, in order to investigate the number of prescribed drugs and drug cost. METHODS: We performed a retrospective study of patients who visited the outpatient clinic of GifuMunicipalHospital and received anti-hypertensive agents between June 2006 and December 2011. RESULTS: No reductions in the number of prescribed drugs or drug cost were seen following a change in prescription to an angiotensin II receptor blocker/diuretic. Patients receiving an angiotensin II receptor blocker/calcium channel blocker had a significant reduction in the number of prescribed drugs and a slight decrease in drug cost. CONCLUSION: In this study, a reduction in the number of prescribed drugs and a decrease in economic burden were not observed after prescription of angiotensin II receptor blocker-containing combination tablets. In order to assess the usefulness of angiotensin II receptor blocker combination tablets, further studies are necessary to investigate their hypotensive effects, safety profile, and other factors.

Pharmaceutical care for patients undergoing s-1 plus Cisplatin therapy for unresectable recurrent gastric cancer.

We examined the adverse gastrointestinal events associated with tegafur/gimeracil/oteracil potassium (S-1) plus cisplatin therapy for unresectable recurrent gastric cancer and risk factors for discontinuing therapy due to adverse events. A total of 65 subjects who had received S-1 plus cisplatin therapy for gastric cancer at Ogaki Municipal Hospital were examined. We found that the risk factors for discontinuation of the therapy due to adverse events were serum albumin (Alb) level less than 3.5 g/dL (odds ratio [OR]: 321.14, P = .0015), creatinine clearance (CrCl) rate less than 78 mL/min (OR: 35.23, P = .0123), and performance status (PS) more than 1 (OR:12.62, P = .0243). Moreover, grade 3 or 4 nonhematological toxicities (including malaise and anorexia) were significantly higher in subjects with Alb less than 3.5 g/dL and CrCl less than 78 mL/min (P < .01). In conclusion, we should pay attention to the safety and continuity of S-1 plus cisplatin therapy in cases where the Alb level is <3.5 g/dL, CrCl level is <78 mL/min, and PS level is >1. Pharmacists should consider reducing the treatment dosage and providing nutritional support in such cases.

The pivotal role of intracellular calcium in oxaliplatin-induced inhibition of neurite outgrowth but not cell death in differentiated PC12 cells.

The antineoplastic efficacy of oxaliplatin, a widely used anticancer drug, is restricted by its adverse effects such as peripheral neuropathy. Infusing a combination of calcium gluconate and magnesium sulfate (Ca/Mg) suppresses the acute neurotoxic side effects of oxaliplatin, although the mechanism is unclear. To elucidate the molecular mechanisms of oxaliplatin-induced neurotoxicity and the effects of Ca/Mg against this toxicity, we examined the effect of Ca/Mg on oxaliplatin-induced inhibition of neurite outgrowth in PC12 cells, a commonly used neuronal cell model. Oxaliplatin and oxalate suppressed nerve growth factor (NGF)-induced neurite outgrowth and reduced the NGF-mediated increase in the intracellular calcium concentration [Ca(2+)](i). A calcium-chelating agent, BAPTA/AM, also exhibited similar inhibitory effects on neurite outgrowth and [Ca(2+)](i). The addition of Ca/Mg attenuated these inhibitions induced by oxaliplatin and oxalate. The NGF-induced upregulation of growth-associated protein-43 (GAP-43) was suppressed by oxaliplatin and oxalate. Oxaliplatin, but not oxalate, suppressed NGF-stimulated extracellular signal-regulated kinase activation, and this inhibition was not affected by Ca/Mg. Ca/Mg did not modify the oxaliplatin-induced loss of cell viability or apoptosis in PC12 or HCT-116 cells, a human colorectal cancer cell line. These results suggest that the inhibition of neurite outgrowth but not tumor cell death induced by oxaliplatin is partly associated with reductions in [Ca(2+)](i) and GAP-43 expression, and this inhibition was suppressed by the addition of Ca/Mg. Therefore, it may be assumed that Ca/Mg is useful for protecting against oxaliplatin-induced neurotoxicity without reducing the antitumor activity of oxaliplatin.

[Development of skill scale for communication skill measurement of pharmacist].

To purpose of this study was to develop a pharmacist communication skill scale. A 38 items scale was made and 283 pharmacists responded. The original questionnaire consisted of 38 items, with 1-5 graded Likert scale. Completed responses of 228 pharmacists data were used for testing the reliability and the validity of this scale. The first group of items from the original questionnaire were 38, and finally 38 original items were chosen for investigation of content validity, correlation coefficient and commonality. From factor analysis, four factors were chosen among the 31 items as follows: patient respect reception skill, problem discovery and solution skill, positive approach skill, feelings processing skill. The correlation coefficient between this original scale and the KiSS-18 (Social Skill) received high score (r=0.694). The reliability of this scale showed high internal consistency (Cronbach α coefficient=0.951), so the result of test for the validity of this scale supports high content validity. Thus we propose adoption of pharmacist communication skill scale to carry a brief eponymous name as TePSS-31. The above findings indicate that this developed scale possess adequate validity and reliability for practical use.

Direct-injection HPLC method of measuring micafungin in human plasma using a novel hydrophobic/hydrophilic hybrid ODS column.

A direct-injection HPLC-based method has been developed for determining amounts of micafungin in human plasma using a novel hydrophobic/hydrophilic hybrid ODS column. The method is easy to perform and requires only 10 µL of a filtered plasma sample. The chromatographic separations were carried out with a gradient mode. The fluorescence detection wavelengths of excitation and emission were set at 273 nm and 464 nm, respectively. Retention times for micafungin and IS were 22.4 and 23.7 min, respectively. Micafungin and FR195743 (IS) peaks were completely separated with little tailing, and no interference was observed. The calibration curve of micafungin showed good linearity in the range of 0.5-20.0 µg/mL (r(2)=1.00). The intra-day accuracy ranged from -4.5 to 5.3%. The inter-day accuracy ranged from -9.8 to 1.5%. The precisions were less than 10%. This method is useful for the determination of micafungin in human plasma.

[Annual lifelong learning program for pharmaceutical care practice by the Gifu Pharmaceutical University].

Knowledge and techniques involved in medical affairs have been steadily advancing. The lifelong learning programs supported by Gifu Pharmaceutical University are introduced. The 3 unique programs consist of (1) a lifelong learning program concerning recent medical topics provided by our university, (2) a reeducation program containing some lectures and practices concerning the most advanced knowledge and techniques on pharmacy and medicine, provided by co-organization of 3 public universities (Nagoya City University, University of Shizuoka, and Gifu Pharmaceutical University), and (3) an annual lifelong learning program promoted by Gifu Pharmaceutical University Pharmacy. Gifu Pharmaceutical University Pharmacy accommodates 100 prescriptions daily from hospitals. The annual lifelong learning programs held by our pharmacy have comprehensively provided practical knowledge and techniques on newly developed medicines, pharmaceutical care practice, pharmacotherapy, community pharmaceutics, and so on, for the last 10 years. Pharmacists should have full responsibility for pharmacotherapy as health care workers. The pharmacists should make a concerted effort to understand pharmacotherapy through pharmaceutical care practice by cooperation with community pharmacists, hospital pharmacists, and pharmaceutical associations. Our lifelong learning program has contributed to the improvement of pharmaceutical skills and communication among pharmacists, medical doctors, and other health care workers.

[Contribution of the pharmacists to self-care and primary care with nonprescription medications].

Peoples have been much concerned on their healthy life. Recently, many kinds of dietary supplements and food for specified health uses are distributed and consumed in large quantities. Concurrently, medical case insurance in Japan has been accommodating a lot of patients increasingly year by year, when the importance and enlightenment of self-care and primary care of people with nonprescription medications is proposed. The Pharmacists Law defines the responsibility of the pharmacists for the public health and welfare with medication and hygienic affairs. The recent pharmacy education for 6 years in Japan is likely to orient pharmaceutical care practice for contribution to the treatment of patients by appropriate management of medication. The multidisciplinary knowledge on medicines and diseases, and the patient consultation technique are required in the pharmacy practice. The contribution and accountability of the community pharmacists to self-care and primary care with nonprescription medications, as social needs, is expected. In this review, social responsibility on the treatment with nonprescription medications and their information provided by the community pharmacists in future is discussed.

Clonazepam use for prevention of acute and delayed vomiting induced by Cisplatin-based chemotherapy for lung cancer.

We investigated the efficacy of clonazepam as an antiemetic in cisplatin-based chemotherapy for lung cancer. Seven patients experienced cisplatin-induced vomiting despite antiemetic therapy including 5-hydroxytryptamine(3) (5-HT(3)) antagonist and dexamethasone. Therefore, the antiemetic therapy including clonazepam, 5-HT(3) antagonist and dexamethasone was subsequently explored in the next course for the same seven patients. We administered clonazepam (0.5 or 1.0 mg/kg) once a day orally for 5 d from day one prior to chemotherapy. The grade of delayed vomiting, evaluated according to Common Terminology Criteria for Adverse Events Version 3.0, in the courses of therapy with clonazepam was significantly lower than without clonazepam (p=0.013). The patients whose serum clonazepam concentrations were below the lower limit of detection (3.0 ng/ml) experienced vomiting in three of three courses, whereas the patients whose serum clonazepam concentrations were higher than 4.3 ng/ml experienced no vomiting in six of seven courses. We observed that the symptom of cisplatin-induced delayed vomiting is controlled with serum clonazepam levels in the order of 10.0 ng/ml.