Hospitalization period and direct medical cost in patients using warfarin or novel oral anti-coagulants after a cerebral embolism.

Background Warfarin has been used in Japan for a long time in patients after cerebral embolism to prevent recurrence. Recently, several novel oral anti-coagulants (NOACs) have been approved for use and are gradually replacing warfarin. However, it remains unclear whether warfarin and other NOACs differ from each other with respect to drug costs and length of stay (LOS) during treatment in Japan. Objective To assess differences in LOS and direct medical cost between patients after cerebral embolism treated with warfarin and those treated with NOACs. Setting Thirteen acute care hospitals in Japan. Method For hospitalized patients with cerebral embolisms who were treated with NOACs and/or warfarin between April 2012 and March 2014, we assessed LOS for patients with warfarin and NOAC using log-rank test, and stratified proportional hazard regression. Also, we assess direct medical cost using paired-t test. Main Outcome measure LOS and medical cost after first treatment with warfarin and NOAC. Results The median LOS for NOACs-treated patients was 12.5 days and that for warfarin treated patients was 19.0 days while the corresponding mean medical costs were USD 7151 ± 6228 [JPY 736,546 ± 641,437] and USD 8950 ± 5891 [JPY 921,830 ± 606,765]. The drug cost for NOACs-treated patients was higher but costs for laboratory-test and hospitalization were lower than those for warfarin-treated patients. Conclusions For NOAC-treated patients, LOS was shorter, and medical cost during hospitalization tended to be lower than those for warfarin-treated patients, whereas NOACs prices were higher than warfarin price.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

[Effect of pharmacists' intervention on the antibiotic therapy for the methicillin-resistant Staphylococcus aureus (MRSA) infectious diseases in the intensive care unit].

Pharmacists are providing pharmaceutical care in general wards, but it is still not common in the intensive care unit (ICU). However, we have worked in ICU, and recommended the rational dosage regimen of the antibiotics to the physicians during the treatment period. Especially, the patients who were infected with methicillin-resistant Staphylococcus aureus (MRSA) in ICU should be provided appropriate antibiotic therapy, otherwise they have a poor prognosis. The aim of this study is to evaluate usefulness of the pharmacists' intervention on the antibiotic therapy for MRSA infectious diseases in the ICU. We investigated retrospectively the period of anti MRSA drugs administration, the medical cost, which includes cost of anti MRSA drugs and hospital charge, and the initial trough concentration of vancomycin (VCM). The patients with MRSA pneumonia were classified into two groups according to the pharmacists' intervention. The number of the patients who the pharmacists performed dosage regimen of anti MRSA drug was 11 (intervention group) and that of the patients who the pharmacists performed no intervention was 47 (control group). The average period of administration of anti MRSA drugs in the intervention group was significantly decreased in 5 days. Furthermore, if the pharmacists performed dosage regimen of anti MRSA drug to the patients in control group, the medical cost of 10 million yen would be saved. The initial trough concentrations of VCM were not significantly different between two groups. However, the achievement rates are 75.0% in intervention group and 66.7% in control group, if the goal of trough level of VCM is set from 5 to 15 µg/ml. Moreover, there are 75.0% in intervention group and 20.8% in control group, if the goal of trough level of VCM is set from 10 to 20 µg/ml, which is significantly different between the two groups. Therefore, it was suggested that the pharmacists in the ICU contributed to optimize the anti MRSA therapy and reduce the medical cost.

Preventive Effects of Salacia reticulata on Obesity and Metabolic Disorders in TSOD Mice.

The extracts of Salacia reticulata (Salacia extract), a plant that has been used for the treatment of early diabetes, rheumatism and gonorrhea in Ayurveda, have been shown to have an anti-obesity effect and suppress hyperglycemia. In this study, the effects of Salacia extract on various symptoms of metabolic disorder were investigated and compared using these TSOD mice and non-obese TSNO mice. Body weight, food intake, plasma biochemistry, visceral and subcutaneous fat (X-ray and CT), glucose tolerance, blood pressure and pain tolerance were measured, and histopathological examination of the liver was carried out. A significant dose-dependent decline in the gain in body weight, accumulation of visceral and subcutaneous fat and an improvement of abnormal glucose tolerance, hypertension and peripheral neuropathy were noticed in TSOD mice. In addition, hepatocellular swelling, fatty degeneration of hepatocytes, inflammatory cell infiltration and single-cell necrosis were observed on histopathological examination of the liver in TSOD mice. Salacia extract markedly improved these symptoms upon treatment. Based on the above results, it is concluded that Salacia extract has remarkable potential to prevent obesity and associated metabolic disorders including the development of metabolic syndrome.

[Primary care enlightenment to local inhabitants--cooperation of medical institution and community pharmacy in treatment of chronic hepatitis C].

Community pharmacy is evolving to provide additional services to patients such as compliance improvement, self-care and OTC consultations and advising on daily activities to supplement medical treatment. Currently in Japan, it has been estimated that 1.5 to 2 million people have chronic hepatitis C. We have attempted to increase the population's knowledge of this important issue with educational brochures about hepatitis C and placing posters encouraging them to ask medical professionals about their health problems. Peg-interferon and ribavirin combination therapy has an efficacy rate of approximately 60%. The side effects might present in different ways and frequency depending on the treatment duration; therefore, pharmacists should monitor patients carefully during the entire treatment period with particular attention to OTC drug use, daily activity, etc. Additionally, for outpatients community pharmacy has responsibility to avoid drug-related adverse events in the patients' daily life, so monitoring for clinical signs of side effects is necessary. We created the "Clinical Pathway for Healthcare Network of Chronic Hepatitis C Treatment via the Medication Notebook Type" (Clinical Pathway) for patients who received Peg-interferon and ribavirin combination therapy. We are beginning to provide the new version of this service to patients as one of the pharmaceutical care components in the community pharmacy. I would like to describe how we cooperate with other community pharmacies using the "Clinical Pathway", which is to improve patient care in the community pharmacies.

[Clinical evaluation of drug information provided by the pharmacists in the intensive care unit].

Pharmacists working in the intensive care unit (ICU) in Saiseikai Yokohamashi Tobu Hospital are mainly responsible for managing the stock of drugs, providing drug information to other medical staff, educating them for rational drug therapy, and providing pharmaceutical care to the patients. In order to evaluate the contribution to the rational drug therapy, we investigated the acceptance rate of the drug information that the pharmacists in the ICU provided to the physicians from February to May in 2009. The number of cases in which drug information was provided by the pharmacists to the physicians during the period was 288. It was suggested that more than half of the information could optimize the drug dosage regimens and correct the inadequate prescriptions. Furthermore, 98.9% of the information provided by pharmacists was accepted by physicians. We questioned 5 intensivists to evaluate the information with a 5 point scale (maximum score was 4, minimum score was 0) and then the average of score was 3.3. In addition, their evaluation of the information about optimizing the drug dosage regimens marked the highest point (over 3.5). Meanwhile, providing drug information which led the physicians to correct the inadequate prescriptions contributed to reduce the cost of the drug therapy by 900000 yen during the period. As a result, it was suggested that the intensivists highly appreciated the information offered by the pharmacists and the information contributed to enhance high-quality drug therapy. Additionally, the economic impact was identified through the cost reduction in drug therapy.

Cost-minimization analysis of sequence changes between FOLFIRI and FOLFOX6 therapy for advanced colorectal cancer in Japan.

BACKGROUND: Randomized, controlled trials (RCTs) in 220 patients with advanced colorectal cancer reported no significant differences in survival periods between folinic acid/5-fluorouracil/irinotecan (FOLFIRI) and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX6) therapies, irrespective of the treatment sequence. Based on a literature search, an economic assessment of both treatments given in 1 of 2 sequences (FOLFIRI and FOLFOX6, or FOLFOX6 and FOLFIRI) has not been conducted in Japan. OBJECTIVE: The present cost-minimization analysis used a mathematical Markov model to assess health care costs of these 2 treatment sequences from the perspective of National Health Insurance (NHI) in Japan. METHODS: The analysis simulated the expected costs resulting from the influence of treatment sequence in a hypothetical cohort of 10,000 patients with nonresectable advanced colorectal cancer over a period of 100 months using a hypothetical Markov model. Clinical parameters were obtained from the RCTs. Cost parameters included those for physical examination, medication, and personnel. Medication and physical examination costs were based on 2008 NHI drug prices and medical service fees, respectively. Costs were discounted at a monthly rate of 0.4575% (equivalent to an annual rate of 3%). The influence of each parameter (clinical and cost parameters) was assessed using a probabilistic sensitivity analysis by the 10,000-time Monte Carlo simulation. RESULTS: When FOLFIRI was used as the initial treatment in this analysis, costs to the NHI were reduced. On analysis of the influence of each parameter, the expected reduction in costs, compared with FOLFOX administered as the initial treatment, was significant ( 7,787,828 yen [95% CI, 6,098,517 yen - 9,499,952 yen]). CONCLUSIONS: The findings of this cost-minimization analysis suggest that using FOLFIRI followed by FOLFOX versus the reverse strategy produced cost savings from the perspective of the NHI in Japan. However, differences in adverse-events profiles may warrant treatment adjustments in individual patients.

[Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction].

Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.

[Single center survey of the relationship between pregnancy anemia and prepregnancy lifestyle].

Physiologically, anemia often occurs during pregnancy because of an increase in circulating plasma volume. Pregnancy anemia is found prenatally in 50-75% of women. Based on the present survey performed in our obstetrics and gynecology ward, 52% of women experienced anemia during their pregnancy. This suggests that normal physiological changes due to pregnancy alone are not the only factors contributing to pregnancy anemia. Therefore to study the influence of lifestyle on pregnancy anemia, we investigated prepregnancy lifestyles on the assumption that the accumulation of several factors over a long period is usually the cause of anemia. The present results suggest that (i) the probability of anemia is slight in late pregnancy, if a normal Hb concentration is maintained in early pregnancy; (ii) the menstrual cycle is involved in the onset of anemia during early pregnancy; (iii) the number of meals taken and the level of alcohol consumption influence Hb concentration in late pregnancy. We believe that these findings provide a useful information source for advising patients on avoiding pregnancy anemia, which we can also use as guidance for outpatients at puberty. In conclusion, to prevent pregnancy anemia it is important to keep a regular menstrual cycle before pregnancy, and to take 3 meals/day and abstain from alcohol before and during pregnancy.

Efficacy of Tokishakuyakusan on the anemia in the iron-deficient pregnant rats.

Iron-deficiency anemia not only causes insufficient oxygen delivery to the body of the mother, but creates serious conditions in the fetus, such as insufficient oxygen delivery and poor development, and its treatment has become an important issue. To elucidate the mechanism of the anemia-ameliorating action of Tokishakuyakusan, we investigated the effect of administration of Tokishakuyakusan on anemia-related parameters and the serum transferrin and erythropoietin levels, erythrocyte morphology, and bone marrow cells in pregnant rats and in pregnant rats with iron-deficiency anemia. The results showed that Tokishakuyakusan significantly improved the low erythrocyte count, hemoglobin, and hematocrit values of the pregnant rats in the iron-deficient state, increased the proportion of normal erythrocytes in terms of erythrocyte morphology, increased the proportion of erythroblasts among bone marrow cells, and also significantly increased the erythropoietin and transferrin levels in the blood. These findings suggested that Tokishakuyakusan promotes erythrocyte differentiation in iron-deficiency anemia, and that it possesses anemia-ameliorating efficacy.

A comparative study of laboratory parameters and symptoms effected by Toki-shakuyaku-san and an iron preparation in rats with iron-deficiency anemia.

In order to more closely examine the effect of Toki-shakuyaku-san and an iron preparation in vivo in an animal experiment, we prepared anemic rats, divided them into 4 groups, i.e., an untreated group, a Toki-shakuyaku-san group, an iron-preparation group and a Toki-shakuyaku-san+iron-preparation group, and assessed the results of laboratory parameters, hematology, and general symptoms of anemia. The results showed trends toward improvement in indices of anemia, i.e., erythrocyte (RBC) count, hemoglobin (Hb), hematocrit (Ht) and serum iron (Fe), and improvement of anemic symptoms in the 3 treated groups. Examination of erythrocyte morphology showed that erythrocyte destruction had occurred only slightly in the 3 treated groups. The organ weight measurements showed an increase in the weight of the heart and spleen in the untreated group, but tended to be closer to normal in the 3 treated groups. The number and wet weight of the feces in the untreated group were markedly lower than normal, but increased in the Toki-shakuyaku-san group. In the iron-preparation group, the hemorrhage of stomach and pigmentation of the tail which seem to be a side effect of iron were observed, but was not seen in the Toki-shakuyaku-san group. The results animal experiment more closely examined the results of clinical study, and we concluded that by using Toki-shakuyaku-san and the iron preparation in combination, it is possible to lessen the adverse reactions such as gastrointestinal symptoms, and that more ameliorative effect on the anemic state can be expected.

A comparative study of the usefulness of toki-shakuyaku-san and an oral iron preparation in the treatment of hypochromic anemia in cases of uterine myoma.

We prospectively studied and compared the usefulness of Kampo medicine (Sino-Japanese traditional herbal medicine) "Toki-shakuyaku-san" and an oral iron preparation in the treatment of hypochromic anemia associated with uterine myoma. The study subjects consisted of 25 patients who were diagnosed as having hypochromic mild to moderate anemia associated with menorrhagia attributable to uterine myoma. They were divided into the Toki-shakuyaku-san group (n = 10) and the oral iron group (n = 15). We monitored the blood counts, subjective symptoms, and occurrence of side effects after oral administration of either preparation for 4 and 8 weeks in these subjects. In regard to the blood counts and improvements of the laboratory parameters of anemia, while marked improvement was observed in the oral iron group, no significant improvement was noted in the Toki-shakuyaku-san group. On the other hand, in terms of improvement of the signs and symptoms of anemia, such as facial pallor, spoon-shaped nails and dizziness, the latter group also showed significant improvement. In addition in the Toki-shakuyaku-san group, resolution of symptoms such as hypermenorrhea, dysmenorrhea, feeling cold, dizziness, headache and shoulder stiffness was also noted. While side effects were encountered in 80.0% of patients in the oral iron group, no significant side effects were observed in the Toki-shakuyaku-san group. From these findings, it is considered that Toki-shakuyaku-san may be useful for resolving the symptoms of mild or moderate anemia associated with uterine myoma.

Effects of liver-supplemented food on the development of embryos in mice.

We examined whether dietary intake of cattle liver-supplemented food induces reproductive effects in dams and developmental effects in embryos in the mouse model. Seven groups of 19 to 35 female mice each were given either powdered food or the food supplemented with crude liver homogenate, its lipophilic component, the defatted liver homogenate or vitamin A (retinol palmitate) during a 25-d period spanning from a week prior to mating to gestation day 18 (GD18). Fetal mortality and incidence of external abnormalities of the fetuses whose dams were given the diet supplemented with the crude liver homogenate increased dose-dependently with an increase in the supplemented amount of the crude liver homogenate. On the other hand, the defatted liver homogenate did not induce any reproductive or teratological effect. The vitamin A (VA)-supplemented food (950 IU/5 g food as VA) induced approximately the same levels of the incidence of total external abnormalities appearing at the same affected regions or organs as the foods supplemented with the 700 mg crude liver homogenate (1029 IU/5 g food as VA) and its lipophilic component (950 IU/5 g food as VA). The content of VA (as 1029 IU/5 g food) in the crude liver homogenate was found to be approximately equal to that in the lipophilic component (950 IU/5 g food as VA). Therefore, it was concluded that VA plays an important role in induction of the lethal and teratogenic effects in the fetuses whose dams were given the powdered foods supplemented with the crude liver homogenate and its lipophilic component.