The purpose of this study was to develop a tool for detecting connective tissue diseases using subjective symptoms and background data in order to establish appropriate criteria to advise patients in a community pharmacy setting. The medical records of patients admitted to the medical ward of the Internal Medicine Department at Fujita University Hospital, Japan over a 5-year period between December 1995 and January 2001, were retrospectively reviewed. Fifty-eight patients with a fever of over 38. 5t and/or exanthema were found to exhibit drug allergies, and thus were included in this study. Of these, 22 patients were previously diagnosed to have connective tissue diseases. A logistic regression analysis was performed to examine the factors associated with the onset of connective tissue diseases. A univariate logistic regression analysis for several variables showed the factors associated with connective tissue diseases to be age (per year relative risk) (Odds Ratio [OR] : 1.01, 95% confidence interval [95% CI] : 1.00-1.07), ranged onset age (OR : 4.12, 95% CI : 1.48-15.03), gender (OR : 5.07, 95% CI : 1. 27-20.22), anemia (OR : 4.57, 95% CI : 1.18-17.72), fever (OR : 0.32, 95% CI : 0. 11-0.97), and anti-nuclear antibody (OR : 5.14, 95% CI : 1.28-20.68). A multivariate analysis of the former four factors, which may be determined for each patient through interviews in a community pharmacy setting, revealed 3 factors ; namely, the range of the onset age (OR : 6.59, P=0.0006), gender (OR : 5.27, P=0.034) and anemia (OR : 5.21, p=0.041), to be the most important factors for predicting the onset of connective tissue disease. An equation to evaluate the onset of connective tissue diseases was created using the model coefficients for these factors. This equation was thereafter applied to these 58 patients. Predicting diseases with this equation revealed a sensitivity of 81.8%, a specificity of 77.8%, a predictive value for a positive test of 69.2%, and an OR of 15. 8. A logistic regression analysis of several variables revealed 3 factors which were considered to increase the probability of connective tissue diseases onset in patients with fever and/or exanthema. Screening for connective tissue diseases using these factors may thus be a useful tool for evaluating diseases in a community pharmacy setting.
In order to carry out effective warfarin treatment and to avoid unnecessary adverse reactions, patients need to recognize the importance of drug compliance, food-drug interaction, drug-drug interaction, and matters that require attention in daily life. We therefore have conducted a “Warfarin Classroom” since April 2000 to provide proper information about warfarin to outpatients. We evaluated how did “Warfarin Classroom” changed both the knowledge and recognition in these patients using a scoring system. The number of subjects participating in this study was 136 (110 males, 26 females, average age : 61.8 years). The patients filled in the same questionnaire regarding their knowledge about warfarin before and after the medication counseling. In the questionnaire we allocated one point for one correct answer from the patients. The average value of the total score was 6.4 and 7.8 before and after the counseling, respectively. A significant improvement was thus observed after the counseling. The target values of thrombo test are commonly set up at 10-20% and 20-30% in cardiovascular surgery and vascular surgery, respectively. However these values should be adjusted according to patient's disease conditions and side effects. In our study, the patients who maintained the target value set up by individual were 43 % and 60 % before and after the counseling, respectively. As a result, it was found that our “Warfarin Classroom”, in which pharmacists counsel outpatients regarding how to take to warfarin, was useful for improving knowledge and helping the patients achieve a better outcome by improving the target values for the thrombo test.
In 12 patients suspected of drug-associated hemorrhagic colitis, the identification of the allergenic drugs was made based on the findings of a leukocyte migration test (LMT) to study the value of LMT and also based on the presence of an allergic reaction in drug-associated hemorrhagic colitis. The LMT was positive in 8 (67%) of 12 cases. When it was absent in the patient' s serum, the positive rate was 3/12 (25%), whereas when it was present in the serum the rate increased to 7/10 (70%). Leukocyte migration activating factor (LMAF) was detected in 5 cases (42%) and leukocyte migration inhibitory factor (LMIF) was detected in 3 cases (25%). LMT-positive drugs were detected in 9 of all 41 suspected drugs, in which 6 drugs (67%) were β-lactam antibiotics and 2 drugs (22%) were nonsteroidal anti-inflammatory drugs and 1 drug (11%) was a hemostatic drug. Penicillin antibiotics accounted for 67% (4/6) in β-lactam antibiotics. Abnormal growth bacteria, i.e., K.oxytoca, Cl. Difficile, E. coli O-18 were detected in 3 cases by a bacteriological examination of a stool culture. However, all the 3 cases were positive for LMT. Our findings indicate that in drug-associated hemorrhagic colitis, an allergic reaction may play a major role and LMT may be highly useful for identifying such allergenic drugs. As a result, it may be important to add the patient's serum when performing the LMT. In addition, both LMAF and LMIF may be involved in the pathogenesis. β-lactam antibiotics may also be major drugs that can cause allergic hemorrhagic colitis. Furthermore, hemorrhagic colitis may be partly related to drug allergy even in cases where an abnormal growth of bacteria is detected.
Yokohama City University Medical Center has employed an auto ampule dispensing system (AAD) for injectable medicines connected to a computer order entry system since 2000. AAD is able to pick up the appropriate ampules and vials according to the prescription for each inpatient's prescription. After the employing this AAD system, the opportunity for patients to inquire about prescriptions has increased. In this study, we focused our attention on injectable medicines of H2-receptor antagonist (H2-B) and proton pump inhibitor (PPI) from the pharmacist's standpoint regarding the rational use of medicine. After asking physicians about mixing problems and change to internal medicines toward physicians, the percent of these injectable medicines ordered by physicians was decreased to 50 % in a year. The percentage of patients using injectable medicines in spite of simultaneously taking internal medicin or meals decreased from 70% to 50%. The administration period of H2-B and PPI injectable medicine also tended to decrease. The use of this new dispensing system for injectable medicines and the provision of additional information to physicians during the one year period of this study resulted in an improvement in the appropriate use of H2-B and PPI.
Triple therapy (proton pump inhibitor + amoxicilln + clarithromycin) for one week is considered to be thecommon eradication therapy for Helicobacter pylori (H. pylori) infection. The H. pylori eradication rate has been reported to be 87. 5% after the administration of sodium rabeprazole, which is a proton pump inhibitor, along with two antibiotic drugs for one week [H. Miwa et al., Aliment. Pharmacol. Ther., 13, 741-746 (1999)] We performed a retrospective study to evaluate the treatment of 42 patients with H. pylori infection by the administration of sodium rabeprazole with two antibiotic drugs for a twoweek period. As a result, the H. pylori eradication rate was 93 % (39 of 42 patients). A successful healing of thepeptic ulcer with H. pylon was observed in all 39 patients. Side effects such as mild diarrhea appeared in onlyone patient. The triple therapy with sodium rabeprazole, amoxycillin, and clarithromycin for two weeks wastherefore found to be sufficiently effective in healing peptic ulcers with an H. pylori infection.
Due to changes in the roles of pharmacists in the clinical field, a lengthening of the mandatory study period at pharmacy school is currently being considered. We therefore conducted a survey of the practical training included in the postgraduate hospital pharmacy courses with the aim of exploring the possible forms of the longterm practical training which may be necessary in the future. An analysis of eleven reports on practical training in hospitals and 46 questionnaires completed by students who had completed hospital training suggested that the acquisition of patient oriented pharmaceutical care, which is seen as one of the main aims of such training had, to a large extent, been successfully achieved, however, the ability to identify pharmaceutical problems in the clinical environment had not yet been adequately developed in most students. Most students considered hospital training to be a positive experience but also indicated problems regarding the curriculum, coordination between the university and the training institutions, and the resources of the training institutions. In order to educate fully capable pharmacists, closer coordination and cooperation between the universities and the medical treatment institutions is thus called for in future.
The working committee for the proper use of antibiotics was organized at Tokushima University Hospital in March 2002, and the institutional guidelines for the selection and use of antibiotics were established. The infection control team (ICT) also started monitoring the use of particular antibiotics, including third-and fourthgeneration cephalosporins, calbapenems and anti-MRSA antibiotics, and reported on their use in August 2002. To assess these activities, we examined the status of antibiotic use for injections and compared our findings with the previous data. The results were as follows : 1) the reports required were presented in 47% of the total antibiotics used; 2) after starting the surveillance, the use of the third-and fourth-generation cephalosporins and calbapenems shifted to the first-and second-generation drugs, while the use of anti-MRSA drugs clearly decreased; 3) these changes resulted in a savings of more than two million yen in medical expenditures in a month. These results suggest that closely monitoring the use of antibiotics may thus be beneficial not only for promoting the proper use of antibiotics but also for reducing overall medical costs.
Hospital pharmacists must adequately manage their operations (including agent stock, medication history, drug information). Both pharmaceutical management and counseling services need an enormous amount of time for medication history management and the planning and making of records. Methods to improve the efficiency of such work are thus called for. We therefore developed an original pharmaceutical management and counseling support system. Using this pharmaceutical management and counseling support system, patients were able to be managed more efficiently. As a result, the patients could be observed more carefully and they could also ask questions more easily. Due to the improved relationship between pharmacists and patients, the patient drug compliance increased dramatically.
A 55-year-old female had been treated for acute myeloid leukemia (AML) since 1998. In November 2001, she entered a hospital to undergo medical treatment. Her blood pressure at the time of hospitalization was 110/ 78 mmHg. Radiotherapy was carried out and therefore chemotherapy with cytarabine and mitoxantrone was started. Loxoprofen sodium (LOX) was prescribed for a fever which developed during the treatment. After taking LOX, dizziness and perspiration appeared, and the patient's blood pressure declined to 74/47 mmHg. A 40-year-old female had received chemotherapy for the treatment of AML since June 2001. Her blood pressure was 118/74 mmHg and pulse was regular at the time of hospitalization. The electrocardiogram findings were normal. Although myelosupression was remarkable and arrhythmia was observed during the course of therapy, chemotherapy was continued. Chemotherapy with aclarubicin, cytarabine and mercaptopurine was started, and LOX was prescribed for a fever during the treatment. After taking LOX, the patient's systolic blood pressure declined 24 mmHg. In both cases, hypotension was observed 2 to 3 hours after the administration of LOX and it was repeatedly observed after every administration of LOX. The observed cardiac abnormality was considered to be due to residual chemotherapy remaining in the cardiac muscle. We consider that hypotension developed due to some influence on heart function by both the augmentation of the action of LOX and its active metabolite (LOX-OH) due to hypoalbuminemia and increased total body fluid level through the repression of prostaglandin synthesis in the kidney. As a result, the careful monitoring of blood pressure is necessary when co-administrating LOX with chemotherapy in patients with hypoalbuminemia.
There are many medical supplies, which are required to undergo periodical laboratory tests to prevent the occurrence of serious adverse effects. However, it is uncertain as to whether or not such laboratory tests are actually carried out routinely at hospitals. In order to prevent serious adverse effects, it is important to clarify the current performance of the laboratory tests in hospitals and to perform such laboratory tests properly. In this study, we surveyed the current performance of laboratory tests on Flutamide, Ticlopidine, Benzbromarone, Acarbose, and Thiamazole, which have all been recently required to undergo laboratory tests to prevent potential adverse effects. The present study showed the performance rate of proper laboratory tests, based on package inserts, to be 60, 33.3 and 46.2% for Ticlopidine, Acarbose, and Thiamazole, respectively. Surprisingly, the performance rate of proper laboratory tests for Flutamide was zero, in spite of the fact that it is well known to cause serious liver dysfunction. Our findings suggest a poor recognition by medical staff members of the importance of laboratory tests in or-der to prevent adverse effects. It is therefore important to promote the implementation of periodical laboratory tests, and pharmacists should play a significant role in appropriately conducting such needed laboratory tests to avoid the occurrence of serious adverse effects.
Carbamazepine (CBZ), a first-line drug in the treatment of epilepsy, is mainly metabolized in the liver to carbamazepine-10, 11-epoxide (CBZ-epoxide), an active metabolite of carbamazepine. Which is subsequently converted by epoxide hydrolase to trans-10. 11-dihydroxy-10, 11-dihydro-carbamazepine (CBZ-diol). It is well known that the combination of CBZ and valproic acid (VPA), which have an inhibitory effect on epoxide hydrolase, results in an increased serum CBZ-epoxide concentration, and that such drug interaction produces clinically relevant side effects. In the present study, the steady state serum concentrations of CBZ, CBZ-epoxide and CBZ-diol were measured by HPLC in 46 epileptic patients (from 7 months to 19 years of age) who were receiving CBZ monotherapy or 36 epileptic patients (from 1 year to 19 years of age) who were receiving CBZ and valproic acid, in order to investigate the influences of age and the VPA combination on the CBZ metabolism. The concentration ratio of CBZ-epoxide / CBZ in patients receiving CBZ monotherapy decreased with increasing age, but the ratio of CBZ-diol / CBZ-epoxide did not show any significant age dependency. These results suggest that the ability of the biotransformation from CBZ to CBZ-epoxide is higher in younger aged patients. On the other hand, the combination with CBZ and VPA produced a marked increase in the CBZ-epoxide / CBZ ratio and a marked decrease in CBZ-diol / CBZ-epoxide ratio in a VPA serum concentration-dependent manner, thus indicting an inhibitory effect of VPA on epoxide hydrolase. These findings provide evidence that the serum concentration of CBZ-epoxide, an active metabolite of carbamazepine, is higher in younger aged patients and in those with a higher serum concentration of VPA.
Recently, regarding the dispensing of injections by hospital pharmacists, it is increasingly more important to check some incompatibilities to ensure the stability and safety of injections prescribed to inpatients by doctors. Although various information is available on incompatibilities at the time that injection mixtures are pre-pared, such information is not always easily accessible during clinical use. As a result, we developed a computer system to check the compatibilities of various injection mixtures. This system consists of four items to check injection prescriptions : 1) the independent drug indicated by the package insert, 2) the information of compatibility between 2 drugs based on published information and the literature, 3) examples of combination changes which both happen in medical wards, and are obtained from the literature, 4) the physical interactions resulting from pH change examinations for each drug. Furthermore, this system is composed of three master files and it is designed so that such checks can be easily performed. With this system, not only can we check the compatibility of prescribed injections quickly, but we can also provide such information to other medical staff members.
Rapidly disintegrating tablets (“EMP-tablet”, developed by Eisai, Co., Ltd.) are developed based on a formulation that is expected to make the swallowing of medicines easier for patients with mild dysphagia. To evaluate the sensation of the oral administration of such “EMP-tablets”, the authors conducted a study in patients with mild dysphagia. After the administration of both “EMP-tablets” and uncoated compressed tablets of consisting of the same components and the same appearance (plain tablet), the sensation of their oral administration and other benefits such as size and so on, were compared for both tablets. The 25 subjects with mild dysphagia, who participated in the trial were asked to respond to the question “which tablet was easier to swallow?”. The rate of positive responses for the “EMP-tablet” was 76%, which was significantly better (p=0.0013) than the response for the “plain tablet”. Regarding the question about the size of a tablet, although only 28% responded “It is no problem” before oral administration, the response improved to 80% after oral administration. In addition, there was also a statistically significant difference (p=0.0096) in the ratio of patients who required less water for the oral intake of “EMP-tablets” than “plain tablets” (60% vs 16%). Consequently, in patients with mild dysphagia, the clinical benefits of “EMP-tablets” were clearly observed regarding the level of satisfaction during oral administration (tablet size and so on, as well as the required amount of drinking water) in comparison to “plain tablets”.
As one of the causes of malpractice in connection with injection, a lack of knowledge regarding medical supplies has been observed, and therefore more precise information needs to be provided to medical workers by pharmacists. In order to offer the information of medical supplies to a medical worker and qualitatively improve injection. audits, we attempted to develop an injection expenditure system which added an injection information system (the amount of electrolyte and the capacity of infusion information system, a compatibility information system and cautions information system at the time of dissolution, storage) and an injection audit auxiliary system (a patient monitor system and the former patient check system for cancer chemotherapy). In this study, the effects of the injection information and audit auxiliary system on the rational use of injection were evaluated. Compared with the former system, it appeared that these systems are effect for the improved use of such injections. Simultaneously, based on a questionnaire to nurses, it appeared that this system also provides useful information on the infusion capacity, compatibility, the method for dissolution and storage after the dissolution. These results suggested that this system is useful for improving the quality of life of patients and also for the prevention of malpractice suits.
Codes printed on injections can be used to prevent errors in dispensing injections. We therefore carried out a survey on the present status of code printing on injections in 81 pharmaceutical companies. The questionnaire recovery rate was 98.8%. The total number of injections was 2, 200. Code printing was observed on 14.5% of the injections. Some codes could only be utilized by Pharmaceutical companies, while others could not be scanned due to a low terminal accuracy. However, many companies are now considering the necessity of code printing. The findings of this survey suggested a gradual increase in code printing on injections as pharmaceutical companies are increasingly becoming aware of this necessity. In the future, code printing on all injections should be mandatory. In addition, a check system using codes printed on injections should be established at each medical institution in order to prevent the occurrence of medication errors.
In Japan, no report has so far been published which evaluates drug use for scabies. We surveyed the prevalence of scabies and its management. The result showed that scabies is not a rare contagious parasitic skin infection. Since there is no effective and safe drug for scabies on the market, the following medications were found to be used for its treatment : crotamiton (unlabeled use), Benzyl benzoate formulation (compounded), γ-BHC formulation (compounded). Adverse events associated with those drugs were also reported. In most case, the patients did not receive adequate counseling regarding their drug therapy. Physicians and other health care professionals have been frustrated by the lack of effective preventive and therapeutic intervention for scabies. It is therefore necessary to approve a drug to treat scabies and to also establish clear guidelines for the treatment and management of scabies.