A Drug Interaction between Crizotinib and Warfarin in Non-Small-Cell Lung Cancer: A Case Report.

We report a case of increased prothrombin time-international normalized ratio (PT-INR) when crizotinib and warfarin were co-administered. A 74-year-old Japanese woman presented to the hospital with dyspnea, and was diagnosed with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). Three years after surgical resection of the tumor, the patient started crizotinib because of the recurrence of NSCLC. She received 2 mg/day warfarin due to a medical history of cerebral infarction and chronic atrial fibrillation. Before crizotinib initiation, the patient's PT-INR was 2.60. After 7 days of daily doses of crizotinib, the patient's PT-INR increased to 3.65. This case report provides the first evidence of a drug interaction between crizotinib and warfarin.

Genetic background influences nicotine-induced conditioned place preference and place aversion in mice.

This study was designed to determine whether genetic differences influence the rewarding effects of nicotine in 4 inbred strains of mice (DBA/2, BALB/c, C3H, and C57BL/6). Nicotine (subcutaneous) induced a place preference in DBA/2 and BALB/c mice but a place aversion in C57BL/6 mice. A low dose of nicotine produced a significant place preference, whereas a high dose of nicotine produced place aversion in C3H mice. These effects were completely reversed by the nicotinic receptor antagonist mecamylamine. These results strongly suggest that a conditioned state, such as rewarding effects or aversive effects, can be influenced by genetic background.

The activity of palliative care team pharmacists in designated cancer hospitals: a nationwide survey in Japan.

CONTEXT: The role of pharmacists in palliative care has become more important now that they are able to provide medication review, patient education, and advice to physicians about a patient's pharmacotherapy. However, there is little known about pharmacists' activity on palliative care teams. OBJECTIVES: The present study aimed to examine the clinical, educational, and research activities of pharmacists on palliative care teams and pharmacist-perceived contributions to a palliative care team or why they could not contribute. METHODS: We sent 397 questionnaires to designated cancer hospitals, and 304 responses were analyzed (response rate 77%). RESULTS: Of the pharmacists surveyed, 79% and 94% reported attending ward rounds and conferences, respectively. Half of the pharmacists provided information/suggestions to the team about pharmacology, pharmaceutical production, managing adverse effects, drug interactions, and/or rotation of drugs. In addition, 80% of the pharmacists organized a multidisciplinary conference on palliative care education. Furthermore, 60% of the pharmacists reported on palliative care research to a scientific society. Seventy percent of the pharmacists reported some level of contribution to a palliative care team, whereas 16% reported that they did not contribute, with the main perceived reasons for no contribution listed as insufficient time (90%) and/or staff (68%). CONCLUSION: In Japan, pharmacists exercise a moderate level of clinical activity on palliative care teams. Many pharmacists believe that they contribute to such a team and generally place more emphasis on their educational and research roles compared with clinical work.

Rewarding effects of ethanol combined with low doses of morphine through dopamine D1 receptors.

This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats. Ethanol (0.075-1.2 g/kg, intraperitoneal [i.p.]) alone did not induce place preference. A moderate dose (1 mg/kg, s.c.), but not a low dose (0.1 mg/kg), of morphine induced a significant place preference. The combination of ethanol (0.075-0.6 g/kg, i.p.) and 0.1 mg/kg of morphine, as well as low doses of morphine (0.03-0.1 mg/kg, subcutaneous [s.c.]) combined with ethanol (0.3 g/kg, i.p.), induced a significant place preference. The combined effect of ethanol and morphine was significantly attenuated by naloxone (0.3 mg/kg, s.c.), naltrindole (1.0 mg/kg, s.c.), or long-term administration of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, s.c.). These results suggest that the rewarding effect induced by ethanol and a low dose of morphine is mediated by activation of the central opioidergic and dopaminergic systems through dopamine D1 receptors.

A retrospective study of risk factors for infection in cancer patients receiving specialist palliative care.

Preventing infectious diseases in patients with cancer receiving palliative care is extremely important. However, little is known about the factors causing infection in these patients. The aim of this study was to clarify the factors contributing to infection in patients with cancer receiving palliative care. The medical records of each patient were reviewed, and patient characteristics were recorded. Factors that correlated significantly with infection, as revealed by univariate analysis, were performance status, the fall risk assessment score, and venous catheters. Our present study provides further evidence that the fall risk assessment score is a risk factor for infection. Critical infections might be prevented in patients with cancer receiving palliative care by monitoring the above 3 factors.

[Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

[Survey of the drugs remaining in the diskhaler and investigation of cleaning of fluticasone propionate].

When a fluticasone propionate (FP) diskhaler is used to administer inhaled corticosteroid, it has been reported that there is considerable drug residue remaining in the diskhaler after use. The internal structure of the diskhaler is complex, and it is possible that sufficient cleaning of the device is not achieved using the attached brush. In this study, the diskhaler cleaning method was examined using a patient questionnaire. In response to the question on cleaning, 56.3% of patients responded "Having done", and 66.7% responded to the question on the frequency of the cleaning, "When I use it". Furthermore, cleaning by a healthy volunteer was examined using Rotadisk for inhalation practice. When the group that did not perform cleaning was compared with the group that performed cleaning with the brush, the amount of the lactose adhesion was significantly lower in the cleaning group. When the no-cleaning group was compared with the group that shook off the excess residue from the tray and the main body of the diskhaler, the group that shook off the diskhaler components showed a significantly lower amount of lactose adhesion. It was confirmed that drug residue were able to accumulate, and the shaking off method appeared to have an effect equal to that of cleaning with the brush. It seems that providing patients with guidance not only about the method of inhaling with the diskhaler but also about cleaning of the device is an important area of pharmacy patient management.

Prediction of aminoglycoside response against methicillin-resistant Staphylococcus aureus infection in burn patients by artificial neural network modeling.

OBJECTIVE: To predict the response of aminoglycoside antibiotics (arbekacin: ABK) against methicillin-resistant Staphylococcus aureus (MRSA) infection in burn patients after considering the severity of the burn injury by using artificial neural network (ANN). Predictive performance was compared with logistic regression modeling. METHODOLOGY: The physiologic data and some indicators of the severity of the burn injury were collected from 25 burn patients who received ABK against MRSA infection. A three-layered ANN architecture with six neurons in the hidden layer was used to predict the ABK response. The response was monitored using three clinical criteria: number of bacteria, white blood cell count, and C-reactive protein level. Robustness of models was investigated by the leave-one-out cross-validation. RESULTS: The peak plasma level, serum creatinine level, duration of ABK administration, and serum blood sugar level were selected as the linear input parameters to predict the ABK response. The area of the burn after skin grafting was the best parameter for assessing the severity of the burn injury in patients to predict the ABK response in the ANN model. The ANN model with the severity of the burn injury was superior to the logistic regression model in terms of predicting the performance of the ABK response. CONCLUSION: Based on the patients' physiologic data, ANN modeling would be useful for the prediction of the ABK response in burn patients with MRSA infection. Severity of the burn injury was a parameter that was necessary for better prediction.

Contributions of pharmacists through the promotion of proper drug use.

The contents of pharmacist interventions, which were carried out by the ward pharmacists in their routine pharmacy service activities, were sorted and analyzed to evaluate the contributions of pharmacists. In the ward where pharmacists were stationed, there were a total of 196 cases of pharmacist intervention. The prescription was changed in 170 cases, giving a rate of prescription change of 86.7%. The breakdown of the pharmacist intervention was as follows: "efficacy/safety", 106 cases, followed by "dosage regimen" (48 cases) and "compliance" (10 cases). Cost savings achieved during the investigation period were calculated to be 440,639 yen, and cost avoidance was valued at 1,941,847-3,883,695 yen using the Diagnosis Procedure Combination (DPC). The results of the present investigation showed that pharmacists contribute to through not only their pharmacy services, but also through the promotion of proper drug use and risk management, thereby contributing to hospital management through cost savings and avoidance.

[The role in cancer chemotherapy of "a pharmacist specialized in cancer"].

A pharmacist system specialized in cancer has been established to authorize a clinical pharmacist to provide safe and sure support for cancer chemotherapy. A pharmacist specialized in cancer supports a protocol that has became complicated or involves management of anticancer agent side effects from a professional standpoint. The examination certifying a pharmacist specialized in cancer is very difficult, sophisticated (certification by pharmacists society) and requiring first-hand clinical experience of cancer chemotherapy to be eligible necessary for the examination. 41 pharmacists specialized in cancer were qualified in March of 2006.

Pharmaceutical cost comparison analysis of antimicrobial use for surgical prophylaxis on gastrectomy patients in a tertiary care hospital.

The present study investigated the clinical effects and therapeutic cost of cefazolin (CEZ) and ampicillin/sulbactam (SBT/ABPC) compared to analyze cost-effectiveness for surgical prophylaxis in gastric cancer patients. 157 inpatients who underwent surgery for gastric cancer were investigated. There was no difference between the two groups with regard to sex, age, incidence of complication, stage of cancer, operative time and blood loss, length of hospitalization, the appearance of systematic inflammatory responses syndrome and the prophylactic effect of infection. Meanwhile, decision analysis indicated that the anticipated therapeutic cost per patient in CEZ group was less than that of SBT/ABPC group (USD 142.72 and USD 187.17, respectively). In this case, CEZ use was more cost-effective, insofar as only drug cost was considered.

Structural equation modeling of qualification of pharmacists to improve subjected quality of life in cancer patients.

PURPOSE: To establish structural equation model (SEM) of subjected quality of life (QOL) in cancer patients taking into account qualification of pharmacists. METHOD: The SEM model was constructed from correlation matrix of the scores of answers of questions to both patients and pharmacists. Data were collected from 15 cancer patients who hospitalized and took opioid analgesics for pain control. The patients were asked 18 questions and pharmacists were asked seven questions. From the correlation matrix among scores of answers, a reasonable model was explored by SEM. RESULTS: Health-related QOL (HRQOL) in cancer patients can be modeled by latent variables consist of contributions from physical, emotional and functional domains. The fitting between data and the model was acceptable by statistical goodness-of-fit (GOF) index. The modeled HRQOL by SEM was weakly correlated with subjected QOL in patients, indicating that subjected QOL in patients would be affected not only by above latent variables but other variables. The model taking into account qualification of pharmacists to improve subjected QOL in patients was also made by SEM. The model was reasonably explained and fitting between data and the model was acceptable from some statistical index. The final model suggests that pharmacist can raise subjected QOL in patients through restraining unpleasant side effects. CONCLUSION: The qualification of pharmacists to improve subjected QOL in patients can be modeled by SEM. The final model suggests that pharmacists with qualification to assess patients' pain status contribute to raise subjected quality of life in cancer patients.

[Management of cancer chemotherapy for outpatients--effectiveness of using cancer chemotherapy protocol database for outpatients].

The present study investigated that a cancer chemotherapy protocol registration system was a safe management of cancer chemotherapy for outpatients. A protocol database was made with a personal computer and 122 protocols for 15 diseases were registered until the end of April 2005. As a result, it was easy to check injection prescriptions. Sixty-one errors including 13 dosage errors for 2409 prescriptions were corrected. The time to check prescriptions were shortened, preparation and dosage mistakes were prevented, and stocking drug decreased by dissolution liquids being made with a standardization of using the same bottle (the cost of stocking drug: 40,418 yen). Therefore, the system and database are effective in raising safety of treatments and an increase in efficiency.

[Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway].

The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days. The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future.

Artificial neural network modeling to predict the plasma concentration of aminoglycosides in burn patients.

The goal was to use an artificial neural network model to predict the plasma concentration of aminoglycosides in burn patients and identify patients whose plasma antibiotic concentration would be sub-therapeutic based on the patients' physiological data and taking into account burn severity. Physiological data and some indicators of burn severity were collected from 30 burn patients who received arbekacin. A three-layer artificial neural network with five neurons in the hidden layer was used to predict the plasma concentration of arbekacin. Linear modeling for prediction of plasma concentration and logistic regression modeling for the classification of patients were also used and the predictive performance was compared to results from the artificial neural network model. Dose, body mass index, serum creatinine concentration and amount of parenteral fluid were selected as covariates for the plasma concentration of arbekacin. Area of burn after skin graft was a good covariate for indicating burn severity. Predictive performance of the artificial neural network model including burn severity was much better than linear modeling and logistic regression analysis. An artificial neural network model should be helpful for the prediction of plasma concentration using patients' physiological data, and burn severity should be included for improved prediction in burn patients. Because the relationship between burn severity and plasma concentration of aminoglycosides is thought to be nonlinear, it is not surprising that the artificial neural network model showed better predictive performance compared to the linear or logistic regression models.

[The analysis of prescription frequency and the factors on adverse reactions of NSAIDs for post-operative pain in orthopedic patients].

Recently, adverse reaction of non-steroidal anti-inflammatory drugs (NSAIDs) is the critical problem, although NSAIDs are one of the most commonly used classes of medications worldwide. Therefore, it is worthwhile to investigate the prescription frequency and the factors on adverse reactions of NSAIDs for post-operative pain in orthopedic patients of our hospital. In orthopedic field, loxoprofen was most prescribed in various kinds of NSAIDs. Logistic regression analysis strongly indicated that previous adverse reaction or allergy caused by drugs (not NSAIDs) or food is the important role in the adverse reaction of NSAIDs. In addition, significant correlation was observed between previous illness of gastrointestinal ulcer and gastrointestinal complication of NSAIDs. Moreover, the present study point out that pharmacist clinical intervention against the adverse reaction of NSAIDs may be saved on medical costs. Although further investigation may be needed, these present studies provide the good information for our medication management and instruction tasks (i.e. pharmaceutical care and counseling for inpatients) for post-operative pain of orthopedic patients.