Calcineurin inhibitors are used as immunosuppressive agents for graft-versus-host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation.Since azole antifungals are frequently used for prophylaxis and treatment of infection under immunosuppressive therapy,it is highly possible that azole antifungals will affect blood concentrations of calcineurin inhibitors by inhibiting the drug metabolizing enzyme cytochrome P450 (CYP) 3A4.However,dosage adjustment with individual azole antifungals when administered by different routes has yet to be fully examined.
In this study,we examined the effect of azole antifungals on blood concentrations of tacrolimus administered by intravenous constant infusion and cyclosporine administered orally in hematopoietic stem cell transplant patients.Oral voriconazole increased the blood concentration/dose (C/D) ratio of tacrolimus 2.7-fold,a significant increase.Oral itraconazole and intravenous voriconazole increased the C/D ratio 2.4-fold and 2-fold,respectively,but these changes were not statistically significant.The effects of oral and intravenous fluconazole were less potent than those of voriconazole and itraconazole,and tended to increase the C/D ratio of tacrolimus by 1.5-fold.The potencies of interactions between these azole anitifungals and oral cyclosporine blood concentrations were similar to those for intravenous tacrolimus.
In consideration of these results,the dosages of calcineurin inhibitors should be reduced by 50-65% when concomitantly administered with voriconazole or itraconazole,and by around 35% in the case of fluconazole.However,dosage adjustment for these drugs should also be based on therapeutic drug monitoring because of the large inter-individual variability of pharmacokinetic interactions.

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The Face Scale consists of a set of 6 faces that vary in the level of overt distress expressed.Subjects choose 1 face from the series of pain-expressing faces that best represents the current status of their pain.However,it is an ordinal scale that does not ensure equivalence for the differences between faces.
In this study,we conducted 2 experiments with the objective of evaluating the differences between faces and creating a pain scale that is easy to use in pain assessment.In experiment 1,the pain intensity evoked by 6 faces was measured using Scheffe’s method of paired comparisons,and each face was converted to a position within a 100-mm linear pain scale depending on the pain intensity.By doing this,we created a pain scale in the form of a Labeled Face Scale graduated at 0.00,10.02,18.61,40.31,62.22 and 100.00.In experiment 2,patients’pain was measured and compared using the Labeled Face Scale and a magnitude estimation method.Correlation analysis showed that there was a positive correlation between them (R²=0.8127)and Bland-Altman analysis showed that the majority of plots (94.4%) fell within the coefficient of repeatability (±2 SD).
These results lead us to conclude that the Labeled Face Scale is a useful assessment tool for pain management.

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In the clinical setting,the frequency of adverse effects is directly linked to treatment results but during chemotherapy,they are unavoidable.One of them is stomatitis,a distressing toxic effect.In patients receiving myelosuppressive chemotherapy for solid tumors,the prevalence of stomatitis is 5-40% while its prevalence in patients receiving stem cell transplantation is 75-100%.Stomatitis-associated pain is the main source of cancer treatment-related pain and in some patients it is so severe that narcotic analgesia is required.
Oxidative stress may also be associated with chemotherapy-induced stomatitis and a mouthwash containing allopurinol,rebamipide and camostat for the removal of free radicals is widely used for the prevention and treatment of such stomatitis.However,such agents are not covered by the Japanese National Health Insurance scheme and there is little scientific evidence for their antioxidative properties and effectiveness in the prevention and treatment of chemotherapy-induced stomatitis.We therefore attempted to establish a more useful mouthwash.In the first part of this study,we investigated the antioxidant properties of various compounds.We then used H₂O₂-induced HO-1-N-1 cell injury as a model of stomatitis and found that epigallocatechin gallate had a strong preventive effect against it.Epigallocatechin gallate would therefore be a good component of a mouthwash for the prevention of stomatitis in patients undergoing cancer chemotherapy.

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Teicoplanin is a glycopeptide antibiotic that is highly effective against methicillin-resistant Staphylococcus aureus (MRSA).However,it is recommended that a loading procedure is used to enable teicoplanin to rapidly reach optimal plasma trough levels.Fosfomycin,a cell wall synthesis-inhibiting antibiotic,prevents biofilm formation through the inhibition of penicillin-binding protein 2’in MRSA.
We report a case in which teicoplanin and fosfomycin had a marked synergistic effect in a patient with a serious MRSA infection,in whom C-reactive protein levels stayed high despite teicoplanin having reached an optimal plasma concentration.The combination of fosfomycin and teicoplaninachievedobviousimprovementsininflammatorymarkersandMRSAwas eradicated from the blood and sputum.

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We provided training to students to raise their understanding of patient compliance instruction as part of the community pharmacy practice curriculum in our pharmacy school.In this study,we investigated whether the training made patient compliance instruction worthwhile to students,and analyzed their thinking processes in this respect in order to clarify the process of professional socialization.The questionnaire used for these purposes consisted of 27 questions on learning and 1 extra question on whether students felt patient compliance instruction was worthwhile.Responses were evaluated according to a 7 point scale and it was given to 128 students who participated in the training in 2007.Questions on learning were prepared by the KJ-method based on the reports of 43 students who participated in patient compliance instruction training in 2006.The average for the response to the question on whether patient compliance instruction training is worthwhile was 6.27 (max.7).Further,factor analysis on the responses of 124 students who completed all items of the questionnaire,produced three factors:“skills required for patient compliance instruction”,“difficulty of patient compliance instruction”and “need for pharmacist intervention”.In addition,covariance structure analysis suggested that through the training,students felt the“difficulty of patient compliance instruction” which provided the opportunity to be aware of the“skills required for patient compliance instruction” and the“need for pharmacist intervention”.These two factors seemed to be involved in the thinking process by which students felt that patient compliance instruction was worthwhile.

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Pregnancy is a contraindication for oral calcium blockers in Japan.However,based on the existence of a guideline for the treatment of hypertension and a previous survey,it seems that oral calcium blockers are in fact used for the management of hypertension in pregnant women.With this in mind,we conducted a questionnaire survey on experience of using calcium blockers for the management of hypertension in pregnancy and attitudes towards this.We sent the questionnaire to 291 hospitals and 300 departments of internal medicine in hospitals with obstetrics and gynecology facilities,and received the responses by mail.We received 116 responses from the hospitals and 52 from the obstetrics and gynecology facilities,115 and 50 of which were analyzable,respectively.Although 75% of the hospitals had unified policies for medication in this respect,policies varied among hospitals,and between obstetricians and internists.Approximately half of the respondents were using calcium blockers,with most of them selecting sustained release formulations of nifedipine or nicardipine and only small number of them using long-acting calcium blockers.While many respondents (67%) were considering using calcium blockers for the management of the hypertension in pregnancy,it appeared that other doctors felt that their use should be limited because it was unclear whether they were safe in pregnancy or not,or due to the contraindication in Japan.Further studies are therefore required to clarify the safety of calcium blockers for pregnant women and fetuses.

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Falls among the elderly account for 20% of all incident reports in hospitals and this has triggered debate on the state of care of bedridden patients.In this regard,as well as being an important issue in medical risk management,clarifying the risk factors for falls and taking measures to prevent them will contribute to the objectives of curing diseases and improving the quality of life of patients by ensuring that treatment is continuous,and reduce medical costs.In this study,we focused on carcinoma patients being treated with anticancer drugs,and examined the relevance of these 2 factors to fall incidence.First,we conducted an investigation of fall incident reports and the associated clinical records,and examined the medicines prescribed to the patients concerned.The risk of falls was analyzed by means of case-control studies or the case crossover method.About 40% of all cases of falls involved cancer patients,though such patients accounted for only around 20% of all inpatients.This made the unadjusted odds ratio for the risk of falling in cancer patients 3.22 which tended to be higher than that in patients with other diseases.Analysis of the drug-related fall risk revealed that the unadjusted odds ratio for risk of anticancer drug use in falls was 2.15,indicating that this was a relevant risk.
In conclusion,our findings suggest that extra attention should be paid to cancer patients undergoing chemotherapy in order to prevent fall accidents.

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The hazardous effects of insoluble microparticles generated in injections has been a matter of concern for some time and recently,plastic ampoules have been developed for injection containers as a means of decreasing particle contamination on opening ampoules.To our knowledge,as no studies have been done on insoluble microparticle contamination arising when plastic ampoules are opened,we performed the present study to compare particle contamination from glass ampoules on opening with that from plastic ones and assessed the contribution of the ampoule material to particle generation.We observed that insoluble microparticle contamination from plastic ampoules was significantly lower than that from glass ampoules and therefore conclude that the amount of insoluble particles appears to be relatedtothematerialoftheampouleand recommend using plastic ampoules to prevent microparticle contamination.

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