Evaluation of the Direct Costs of Managing Adverse Drug Events in all Ages and of Avoidable Adverse Drug Events in Older Adults in Japan.

In Japan, medical costs are increasing annually, and the increase in national medical costs, particularly in the direct cost of managing adverse drug events, is high. An in-depth understanding of these costs is important for their reduction. This study aimed to calculate the direct cost of managing adverse drug events in all ages, including older adults, and that of avoidable adverse drug events in older adults. We conducted a retrospective survey on patients aged 1 year or older who visited Gifu Municipal Hospital in Japan. We investigated and calculated the direct cost of managing adverse drug events and that of avoidable adverse drug events based on the Beers Criteria Japanese version (BCJ) and "Guidelines for medical treatment and its safety in the elderly 2015" (GMTSE-2015) in inpatients and outpatients. Among 6,504 patients, 11.1% visited the hospital or were hospitalized due to adverse drug events. The direct costs per patient with adverse drug events were 21,281 and 22,590 yen (166 and 176 euros as on September 13, 2021) for outpatients, and 853,175 and 874,582 yen (6,648 and 6,815 euros) for inpatients of all ages and older adults, respectively. The direct costs of avoidable adverse drug events per patient using drugs listed in the BCJ and GMTSE-2015 for older adults were 3,212 and 3,341 yen (25 and 26 euros) for outpatients, and 55,548 and 80,246 yen (433 and 625 euros) for inpatients, respectively. In sum, considering both inpatients and outpatients in the whole country, the direct costs of managing adverse drug events were 804.53 billion and 597.19 billion yen (6,269 million and 4,653 million euros) per year for all ages and older ages, respectively. The direct cost of avoidable adverse drug events in older adults was 83.43-258.44 billion yen (650-2,013 million euros) per year. We found that, in Japan, high medical costs are often caused by managing adverse drug events, and that the costs of avoidable adverse drug events in older adults based on the BCJ and GMTSE-2015 account for a substantial proportion of the medical cost. Therefore, by using the BCJ and GMTSE-2015, avoiding adverse drug events and reducing medical costs may be possible.

What activities of daily living at discharge affect the discharge destination of patients in an acute-care hospital in Japan: A retrospective factor analysis.

It is important to clarify the influence of activities of daily living (ADL) at discharge on the discharge destination of hospitalised patients. The Functional Independence Measure (FIM) is a widely used ADL assessment scale. In this retrospective study, we aimed to identify what ADL based on FIM at discharge affect the discharge destination of hospitalised patients in an acute-care hospital, in addition to how nutritional status and the number of drugs used, as well as types of disease, affect discharge-to-home. We surveyed age, sex, disease type, length of hospital stay, discharge destination, FIM score at discharge, serum albumin level, and the number of continued drugs in hospitalised patients who underwent rehabilitation in Gifu Municipal Hospital (Gifu, Japan) between January 2014 and December 2014. Multiple logistic regression analysis was performed with discharge to home as a dependent variable and age, sex, disease, FIM score and polypharmacy as independent variables. Multiple logistic regression analysis indicated that a significantly high percentage of discharged-to-home patients were associated with 'self-care' (≥33 points; OR: 2.03), 'sphincter control' (≥14 points; OR: 1.49), 'transfers' (≥13 points; OR: 1.94), and 'locomotion' (≥7 points; OR: 3.55), among others. High FIM sub-scale scores at discharge for self-care, sphincter control, transfers, and locomotion were clarified as factors associated with discharge-to-home. These findings of the association of ADL based on FIM and discharge destination would be useful in deciding discharge destinations for patients in an acute-phase hospital.

The association between polypharmacy and the efficiency of the functional independence measure in an acute-stage hospital: a retrospective cohort study.

BACKGROUND: The Functional Independence Measure (FIM) evaluates the activities of daily living (ADL), and FIM efficiency represents daily improvement in FIM. Polypharmacy affects both ADL and FIM; however, few studies have evaluated its relationship with FIM efficiency. AIM: This retrospective study investigated the effect of polypharmacy on FIM efficiency in patients undergoing rehabilitation at our acute care hospital in 2014. METHODS: We collected data on the patients' age, sex, diagnosis, length of hospital stay, type and duration of rehabilitation, indications for rehabilitation, FIM score before and after rehabilitation, and number of pharmaceuticals being used. Polypharmacy was defined as the administration of five or more pharmaceuticals. Using propensity score matching, we compared the FIM efficiency between the polypharmacy and non-polypharmacy groups (sub-scales and totals). RESULTS: A total of 2455 patients were included. The analytical population included 2168 patients. The analytical population used for propensity score matching included 727 patients in each group (total: 1454 patients). The following FIM sub-scale items were found to be associated with significantly low FIM efficiency in the polypharmacy group: self-care (polypharmacy group FIM efficiency: 0.43 points/day, non-polypharmacy group FIM efficiency: 0.54 points/day) and sphincter control (0.11 points/day and 0.18 points/day, respectively). No significant differences in the FIM efficiency were observed either for any other sub-scales or for totals. DISCUSSION: In the polypharmacy group, self-care and sphincter control, in particular, were associated with inhibited improvement in ADL and FIM. CONCLUSIONS: Reducing polypharmacy among acute-phase patients would allow an earlier return to their normal daily lives.

Efficacy and Safety of Enzalutamide in a Real-World Cohort of Japanese Patients With Castration-resistant Prostate Cancer.

BACKGROUND/AIM: It has been reported that some adverse events (AEs) of enzalutamide (ENZ) occur more frequently in Japanese patients with castration-resistant prostate cancer (CRPC) due to higher steady-state trough plasma concentrations of ENZ (CSS, ENZ) and its active metabolite (NDE), (CSS, NDE). Thus, we investigated the efficacy, safety, and pharmacokinetics of ENZ in Japanese patients with CRPC. PATIENTS AND METHODS: Fourteen patients were administered ENZ at a standard dose (160 mg/day) or reduced doses (80 or 120 mg/day). Prostate-specific antigen (PSA), AEs, CSS, ENZ, and CSS, NDE were examined. RESULTS: A maximum PSA decrement of ≥50% from baseline was achieved in 92% of patients. AEs were few (>20%) and mild. No differences in CSS, ENZ and CSS, NDE between other ethnic groups in previous literature and our subjects was observed. CONCLUSION: ENZ shows adequate efficacy and safety in Japanese patients with CRPC, even if administered at reduced doses in real-world conditions.

Effects of the number of drugs used on the prevalence of adverse drug reactions in children.

In pediatric individuals, polypharmacy would increase the prevalence of adverse drug reactions (ADRs). However, there is no report on the ADR increase adjusted for the influence of concomitant disease types. We conducted a retrospective study in pediatric patients to determine whether polypharmacy is a risk factor for ADR development, after the adjustment. Patients aged 1-14 years on medication who visited Gifu Municipal Hospital (Gifu, Japan) were included. We evaluated patient characteristics, ADR causality, ADR classification and severity, and ADR-causing drugs. We examined the association between ADR prevalence and number of drugs used. We performed multiple logistic regression analyses to investigate risk factors for ADR development. Of 1330 patients, 3.5% sought medical attention for ADRs. ADR causality was most often assessed as "possible," with gastrointestinal ADRs being the most common. Grade 1 ADRs were the most and antibiotics were the most common suspected ADR-inducing drug. The multiple logistic regression analysis showed that ≥ 2 or ≥ 4 drug use, neoplasms, mental and behavioral disorders, and circulatory system diseases significantly increased ADR prevalence. Polypharmacy increased the prevalence of ADR resulting in hospital visits in children, after adjusting for the influence of disease types. Therefore, proactive polypharmacy control measures are necessary for children.

[Risk Factors for Anti-PD1 Antibody-Induced Skin Eruptions].

Skin complication caused by anti-programmed cell death-1(PD1)antibody is a typical immune-related adverse event. We designed this study to clarify the correlation between risk factors(patient's background and laboratory data)and skin toxicity( rash and eruption, excluding itch)after administration of either nivolumab or pembrolizumab. From February 2016 to January 2018, we evaluated the clinical outcomes of 54 patients who were administered anti-PD1 antibody. The patients were divided into 2 groups: 9 patients with skin eruption caused by anti-PD1 antibody(skin eruption group)and 45 patients without skin eruption caused by anti-PD1 antibody(non-skin eruption group). Univariate analysis revealed a significant difference in eosinophil counts in both the groups before anti-PD1 antibody administration(>300/µL)(p=0.020). Factors with p<0.2 in the univariate analysis and 4 factors, age(<65 years of age), sex(male), allergy(+), and pembrolizumab, likely to be related to the appearance of skin eruption, were examined by multivariate analysis. Consequently, eosinophil count before anti-PD1 antibody administration(>300/µL)was identified as a risk factor (odds ratio: 9.530, 95% confidence interval: 1.260-71.80). In conclusion, we suggest that cases with an increased eosinophil count before anti-PD1 antibody administration(>300/µL)may be associated with the appearance of skin eruption.

[Construction and Evaluation of a New Support System for Prescription Inspection of Anticancer Drug Injection Preparation via Quality Control].

Using electronic medical charts at the department of pharmacy of Gifu Municipal Hospital, we constructed a new support system for the prescription inspection of anticancer drug injection preparation via quality control. The system comprises: (1)a "regimen inspection sheet" that can be easily used to check the regimen and clinical laboratory data of patients before the administration of anticancer drugs and(2)an "instruction sheet confirming implementation" that can conveniently confirm the latest clinical laboratory data used to decide the administration of anticancer drugs. Using this system, the safety of anticancer drug administration and work efficiency may be improved.

Analysis of Adverse Reactions Caused by Potentially Inappropriate Prescriptions and Related Medical Costs That Are Avoidable Using the Beers Criteria: The Japanese Version and Guidelines for Medical Treatment and Its Safety in the Elderly 2015.

We conducted a retrospective study to investigate adverse drug reactions and associated medical costs among elderly individuals that could be avoided if pharmacotherapy was performed in accordance with the Beers Criteria: the Japanese Version (BCJV) and Guidelines for Medical Treatment and Its Safety in the Elderly 2015 (GL2015). Patients aged at least 65 years who were either hospitalized at Gifu Municipal Hospital between October 1 and November 30, 2014 (n = 1236) or had outpatient examinations at Gifu Municipal Hospital on October 1-2, 2014 (n = 980) were included in the study. The outcomes measured were usage rates of drugs listed in the BCJV and GL2015, incidence rates of adverse drug reactions, and additional costs incurred per patient due to adverse reactions. Among the inpatients, usage rates of drugs listed in the BCJV and GL2015 were 24.0 and 72.4%, respectively, and adverse reactions to these drugs occurred at rates of 3.0 and 8.2%, respectively. Among the outpatients, while the usage rates were 26.2% (BCJV) and 59.9% (GL2015), the incidence rates of adverse reactions were 4.7% (BCJV) and 3.9% (GL2015). The additional costs incurred due to adverse drug reactions ranged from 12713-163925 yen per patient. Our results demonstrate that appropriate use of drugs based on the BCJV and GL2015 can help prevent adverse reactions; this would reduce the overall medical costs.

[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.

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.

Medical and economic factors influencing generic drug use in the Japanese public health system: Influencing factors in different populations.

Factors influencing generic drug use must be considered when new drug policies are established and initiatives are implemented to promote generic drug use. This study was conducted to elucidate medical and economic factors that influence generic drug use in the Japanese public health system by evaluating the degree of generic drug use via a multivariate analysis. We conducted a retrospective study of medications administered to inpatients at Gifu Municipal Hospital (Japan) from November 1 to 14, 2014. Details of inpatients (age, sex, and type of medical insurance) and the drugs administered (prescribing institution, dispensing pharmacy, price, and class) were assessed. A total of 1409 drugs (original, 639; generic, 770) were analyzed. Multivariate analysis showed significant differences in out-of-pocket medical fees [odds ratio (OR), 0.595], drugs prescribed at Gifu Municipal Hospital (OR, 1.811), drugs prepared at a health insurance pharmacy (OR, 1.541), drugs containing the same active substances as in the generic drugs used at Gifu Municipal Hospital (OR, 3.712), and drugs costing ≥30 yen and containing the same active substance/having the same specifications (OR, 0.516). Drugs prescribed at a large key hospital in the community with high adoption rates of generic drugs, drugs containing the same active substances as the generic drugs adopted by the hospital, and drugs prepared at health insurance pharmacies contributed to a more frequent use of generic drugs. By contrast, out-of-pocket medical fees and being prescribed expensive drugs contributed to the less frequent use of generic drugs.

Renoprotective Effect of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus.

Diabetic nephropathy is one of three major complications of diabetes mellitus, often leading to chronic renal failure requiring dialysis. Recently developed dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit renoprotective effects in addition to antihyperglycemic effects. In this study, we retrospectively investigated temporal changes in the renal function index of patients with type 2 diabetes mellitus (DM) and examined the influence of DPP-4 inhibitors on renal function. Patients with type 2 DM (>18 years old) prescribed hypoglycemic agents at Gifu Municipal Hospital for ≥3 months between March 2010 and April 2014 were included in the study. Renal function was evaluated as estimated the decline in 12-month glomerular filtration rate from the baseline in patients receiving and not receiving DPP-4 inhibitors. Patient data from the DPP-4 inhibitor-treated (501 patients, 58.6%) and untreated (354, 41.4%) groups were analyzed using multiple logistic regression analysis, as well as Cox proportional-hazards regression analysis (616, 55.6% and 491, 44.4%, for DPP-4 inhibitors-treated and untreated groups). Multiple logistic regression analysis indicated that DPP-4 inhibitors significantly lowered the estimated glomerular filtration rate (eGFR) decline [20% over 12 months; odds ratio (OR), 0.626; 95% confidence interval [CI], 0.409-0.958; P = 0.031]. Similar results were obtained using Cox proportional-hazards regression analysis (hazard ratio [HR], 0.707; 95% CI, 0.572-0.874; P = 0.001). These findings suggest that DPP-4 inhibitors suppress the decrease of estimated glomerular filtration rate in patients with type 2 DM and show a renoprotective effect.

Establishing an Indicator of Hypokalemia in Patients Receiving Anti-Epidermal Growth Factor Receptor Antibodies.

Risk factors for hypokalemia were analyzed in patients who received anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) at Gifu Municipal Hospital between February 2010 and March 2013. Subjects were 51 patients (27 men and 24 women) with the median age (interquartile range) of 66 (63-72) years. The study period started from the initiation of anti-EGFR MoAbs administration and ended 4 weeks after administration was completed. Patients were categorized into the side effect group if both minimum serum potassium (Min S-K) grade and b grade (pre-treatment S-K grade-Min S-K grade) were B1; otherwise, they were placed into the no side effect group. Univariate analysis for factors to prevent the side effect identified the "concomitant use of hyperkalemia-inducing drugs" to be statistically significant (p=0.010). Multivariate analysis was conducted on factors with a p value of <0.25 in the univariate analysis and on "concomitant use of hyperkalemia-inducing drugs," which was likely to clinically affect S-K decrease, although its p value was >0.25. It showed that "concomitant use of hyperkalemia-inducing drugs" was a significant risk-prevention factor (odds ratio: 0.138, 95% confidence interval[CI]: 0.033-0.581, p=0.007). In conclusion, "concomitant use of hyperkalemia-inducing drugs" is a factor associated with preventing hypokalemia accompanying anti-EGFR MoAbs administration.

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.

[A female chronic myeloid leukemia patient who gave birth after stopping imatinib intentionally but who maintained a major molecular response with interferon].

Imatinib was administrated to a 38-year-old woman with chronic myeloid leukemia(CML). A major molecular response (MMR)(≤5 copies/0.5 µgRNA in Amp-CML detected using the transcription mediated amplification/hybridization protection assay(TMA/HPA)method)was achieved in 18 months. She maintained MMR for 10 months, and wished to become pregnant. Imatinib was stopped intentionally because she wished to plan a pregnancy, but we prescribed interferon alpha (IFN-a)due to the likelihood of the CML recurring after pregnancy. The nausea caused by IFN-a was improved by administrating it during the night, and she gave birth to a healthy baby by a normal delivery, whilst maintaining MMR. In this case, IFN-a treatment gave good clinical results, the patient's prognosis was improved, and she could maintain a good quality of life. We consider this to be an informative example of IFN-a therapy for CML during pregnancy.

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.

The Establishment of Indicators of Thrombocytopenia in Patients Receiving Lenalidomide Therapy.

The onset of thrombocytopenia and related factors was analyzed in patients with multiple myeloma (MM) who were receiving lenalidomide (Len) therapy at the Department of Hematology, Gifu Municipal Hospital between July 2010 and March 2014. We included 28 MM patients (18 males and 10 females) with a median age of 70.5 (range: 55-84) years. The patients were examined from the start of Len therapy until treatment discontinuation, prolongation, or dose reduction. A significant correlation was observed between platelet (Plt) count prior to the start of Len therapy (pre-treatment Plt) and the difference between pre-treatment Plt and the minimum Plt up to the point in time of treatment discontinuation, prolongation, or dosage reduction (min-Plt) (r=0.674, p<0.001). Univariate analysis revealed that factors causing thrombocytopenia of grade 2or above as a side-effect showed a significant difference when the Plt count was below the lower limit of the normal value (<14.0×10(4)/µL)(p=0.011). Factors with p<0.25 in the univariate analysis and daily dosage of Len were examined by multivariate analysis; thus, a Plt count below the lower limit of the normal value was identified as a factor (odds ratio: 15.12, 95% confidence interval [CI]: 1.712-133.5, p=0.015). In conclusion, we suggest that a Plt count below the lower limit of the normal value prior to the start of Len therapy is a prognostic factor for thrombocytopenia as a side-effect of Len therapy.

[Analysis of factors influencing the occurrence of infusion reaction after initial treatment with rituximab].

We investigated factors influencing the occurrence of infusion reactions after initial treatment with rituximab. We included patients who were administered rituximab for the treatment of B-cell non-Hodgkin's lymphoma at the Gifu Municipal Hospital Hematology from February 2010 to March 2013. Fifty-one patients were included; their median age was 72(44-87)years, and 31 were men and 20 were women. We defined the index of infusion reaction as the maximal change in body temperature within 24 hours from the administration of rituximab and evaluated the correlation with change in body temperature and each factor, and differences of change in body temperature between the upper and lower groups divided by standard value of each factor by using the t test without correspondence. The "2,000 U/mL or less group"of soluble interleukin-2 receptor(sIL- 2R)levels and the "over 2,000 U/mL group"showed significant different(p=0.014). The "double value or less group"of a standard value(211 IU/L)and "over double value group"showed significantly different lactate dehydrogenase(LDH)levels (p=0.017). The "lower limit or less group"of the standard value(men: 13 g/dL, women: 12 g/dL)and the "over lower limit group"showed significantly different hemoglobin(Hb)levels(p=0.020). In conclusion, the levels of sIL-2R, LDH, and Hb may predict the occurrence of infusion reaction after the initial administration of rituximab in patients with B-cell non-Hodgkin's lymphoma.

[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.