Tomoya Tachi

Simultaneous separation, metering, and dilution of plasma from human whole blood in a microfluidic system.

In about a 3 min period, we have simultaneously separated plasma from human whole blood and metered and diluted the plasma using a microchip with an interchannel microstructure. The plasma separation was based on both cross-flow filtration and sedimentation of red blood cells in the microchannels. Metering and diluting operations of the plasma were based on volume control of liquid in the microchannels by syringe pumps. On this microchip, we produced plasma diluted by a factor of 6 from whole blood containing theophylline and we observed very little hemolysis. It is possible to separate plasma from one or just several drops of whole blood by using this microchip.

Effects of peptide dimerization on pore formation: Antiparallel disulfide-dimerized magainin 2 analogue

To elucidate the effects of peptide dimerization on pore formation by magainin 2 (MG2), a covalently linked antiparallel dimer of the MG2 analogue [(F5Y, L6C, F16W, I20C-MG2)(2): II] was synthesized based on the dimer structure revealed by our NMR study. The interactions of the dimer with lipid bilayers were investigated by CD and fluorescence in comparison with a monomer analogue (F5Y, F16W-MG2: I). Similar to I, II was found to form a peptide-lipid supramolecular complex pore accompanied with lipid flip-flop and peptide translocation. The pore formed by II was characterized by a slightly larger pore diameter and a threefold longer lifetime than that of I, although the pore formation rate of the dimer was lower than that of the monomer. The coexistence of the dimer and the monomer exhibited slight but significant synergism in membrane permeabilization, which was maximal at a monomer/dimer ratio of 3. Therefore, we concluded that a pentameric pore composed of one pore-stabilizing dimer and three monomers maximized the overall leakage activity in keeping with our kinetic prediction.

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.

Hyponatremia and hypokalemia as risk factors for falls

Background/objectives:Fall accidents may reduce an individual’s quality of life and ability to perform the activities of daily life, and may delay recovery from illness. Consequently, medical institutions need to take measures to prevent falls. There are various risk factors for falls, including advanced age, illness and medication effects. Although hyponatremia and hypokalemia have been reported to increase the rate of falls, how they affect falls is not fully understood.Subjects/methods:We retrospectively examined 2948 patients, ⩾18 years old who had been hospitalized for ⩾3 days at Gifu (Japan) Municipal Hospital between May 2012 and April 2013 to determine the effects of hyponatremia and hypokalemia on the risk of falls. After the patients had been divided into fall and non-fall groups, their data were subjected to univariate and multiple regression analysis to identify significant differences.Results:The univariate analysis results revealed significant differences between the groups in terms of age (⩾65 years); the presence of hyponatremia, hypokalemia, central nervous system disease, cardiovascular disease and/or peripheral nerve/muscular disease; intake of medications that increase the risk of falls; and increased sedative dosage. The multivariate analysis results revealed significant differences between the groups in terms of the presence of hyponatremia (odds ratio (OR), 1.751; 95% confidence interval (CI), 1.020–3.005), hypokalemia (OR, 2.209; 95% CI, 1.280–3.813), central nervous system disease (OR, 2.492; 95% CI, 1.629–3.814) and/or age ⩾65 years (OR, 2.180; 95% CI, 1.242–3.826).Conclusions:The results indicated that the presence of hyponatremia or hypokalemia increases the risk of falls.

Influence of angiotensin II receptor blocker combination tablet prescription on drug number and cost.

Objectives: Combination therapy using an angiotensin II receptor blocker is expected to promote medication adherence and alleviate economic burden among patients by reducing the number of drugs taken, and thereby to lower associated medical costs. In the present retrospective study, we conducted a survey on the use of angiotensin II receptor blocker–containing combination tablets as anti-hypertensive drugs, in particular angiotensin II receptor blocker/diuretic and angiotensin II receptor blocker/calcium channel blocker combinations, in order to investigate the number of prescribed drugs and drug cost. Methods: We performed a retrospective study of patients who visited the outpatient clinic of GifuMunicipalHospital and received anti-hypertensive agents between June 2006 and December 2011. Results: No reductions in the number of prescribed drugs or drug cost were seen following a change in prescription to an angiotensin II receptor blocker/diuretic. Patients receiving an angiotensin II receptor blocker/calcium channel blocker had a significant reduction in the number of prescribed drugs and a slight decrease in drug cost. Conclusion: In this study, a reduction in the number of prescribed drugs and a decrease in economic burden were not observed after prescription of angiotensin II receptor blocker–containing combination tablets. In order to assess the usefulness of angiotensin II receptor blocker combination tablets, further studies are necessary to investigate their hypotensive effects, safety profile, and other factors.

Analyses of non-benzodiazepine-induced adverse events and prognosis in elderly patients based on the Japanese adverse drug event report database

BackgroundThe contents of the guidelines for the use of non-benzodiazepines (Z-drugs) differ slightly between THE JAPANESE SOCIETY OF SLEEP RESEARCH and THE JAPAN GERIATRIC SOCIETY, and the recommended directions are conflicting. Therefore, we analyzed the use of the Japanese Adverse Drug Event Report database (JADER) for identifying adverse events (AEs) caused by Z-drugs and clarifying their occurrence trend and prognosis.MethodsThe signal value for comparison was calculated by using the proportional reporting ratio (PRR) and chi-squared test (χ2) results of data of elderly and non-elderly patients. Among AEs for which signals were detected in the elderly, we determined that those with lower signal values for non-elderly patients that were half the signal value of the elderly should be used with particular caution in the elderly. We also compared the prognoses.ResultsThe AEs with > 1 risk ratio (RR) in elderly and non-elderly patients were regarded as those that should be noted in the prognosis of AEs in elderly patients. Furthermore, 28 AEs were detected in elderly patients’ signals. In this study, in addition to movement disorders such as “falls” and “bone fractures,” identified by two academic societies, signal characteristics of the elderly were obtained for psychiatric disorders and eye disorders.ConclusionsThere was no difference in prognosis, but these disorders could reduce the quality of life of patients. Therefore, we consider that in prescribing appropriate drug therapy for insomnia, attention should be paid to the occurrence of the AEs caused by the Z-drugs revealed by this study and the guidelines.

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.

A New Search Method Using Association Rule Mining for Drug-Drug Interaction Based on Spontaneous Report System

Background: Adverse events (AEs) can be caused not only by one drug but also by the interaction between two or more drugs. Therefore, clarifying whether an AE is due to a specific suspect drug or drug-drug interaction (DDI) is useful information for proper use of drugs. Whereas previous reports on the search for drug-induced AEs with signal detection using spontaneous reporting systems (SRSs) are numerous, reports on drug interactions are limited. This is because in methods that use “a safety signal indicator” (signal), which is frequently used in pharmacovigilance, a huge number of combinations must be prepared when signal detection is performed, and each risk index must be calculated, which makes interaction search appear unrealistic. Objective: In this paper, we propose association rule mining (AR) using large dataset analysis as an alternative to the conventional methods (additive interaction model (AI) and multiplicative interaction model (MI)). Methods: The data source used was the Japanese Adverse Drug Event Report database. The combination of drugs for which the risk index is detected by the “combination risk ratio (CR)” as the target was assumed to be true data, and the accuracy of signal detection using the AR methods was evaluated in terms of sensitivity, specificity, Youdens index, F-score. Results: Our experimental results targeting Stevens-Johnson syndrome indicate that AR has a sensitivity of 99.05%, specificity of 92.60%, Youdens index of 0.917, F-score of 0.876, AI has a sensitivity of 95.62%, specificity of 96.92%, Youdens index of 0.925, and F-score of 0.924, and MI has a sensitivity of 65.46%, specificity of 98.78%, Youdens index of 0.642, and F-score of 0.771. This result was about the same level as or higher than the conventional method. Conclusions: If you use similar calculation methods to create combinations from the database, not only for SJS, but for all AEs, the number of combinations would be so enormous that it would be difficult to perform the calculations. However, in the AR method, the “Apriori algorithm” is used to reduce the number of calculations. Thus, the proposed method has the same detection power as the conventional methods, with the significant advantage that its calculation process is simple.

A simple method for exploring adverse drug events in patients with different primary diseases using spontaneous reporting system

BackgroundPatient background (e.g. age, sex, and primary disease) is an important factor to consider when monitoring adverse drug events (ADEs) for the purpose of pharmacovigilance. However, in disproportionality methods, when additional factors are considered, the number of combinations that have to be computed increases, and it becomes very difficult to explore the whole spontaneous reporting system (SRS). Since the signals need to be detected quickly in pharmacovigilance, a simple exploration method is required. Although association rule mining (AR) is commonly used for the analysis of large data, its application to pharmacovigilance is rare and there are almost no studies comparing AR with conventional signal detection methods.MethodsIn this study, in order to establish a simple method to explore ADEs in patients with kidney or liver injury as a background disease, the AR and proportional reporting ratio (PRR) signal detection methods were compared. We used oral medicine SRS data from the Japanese Adverse Drug Event Report database (JADER), and used AR as the proposed search method and PRR as the conventional method for comparison. “Rule count ≥ 3”, “min lift value > 1”, and “min conviction value > 1” were used as the AR detection criteria, and the PRR detection criteria were “Rule count ≥3”, “PRR ≥ 2”, and “χ2 ≥ 4”.ResultsIn patients with kidney injury, the AR method had a sensitivity of 99.58%, specificity of 94.99%, and Youden’s index of 0.946, while in patients with liver injury, the sensitivity, specificity, and Youden’s index were 99.57%, 94.87%, and 0.944, respectively. Additionally, the lift value and the strength of the signal were positively correlated.ConclusionsIt was suggested that computation using AR might be simple with the detection power equivalent to that of the conventional signal detection method as PRR. In addition, AR can theoretically be applicable to SRS other than JADER. Therefore, complicated conditions (patient’s background etc.) that must take factors other than the ADE into consideration can be easily explored by selecting the AR as the first screening for ADE exploration in pharmacovigilance using SRS.

Impact of pharmacist counseling on reducing instances of adverse events that can affect the quality of life of chemotherapy outpatients with breast Cancer

BackgroundIn 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.MethodsTo 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.”ResultsTwenty 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.ConclusionsThe 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 registrationNo. UMIN000027171, Registration date: Apr 27, 2017. Retrospectively registered.