細菌感染症治療における薬物治療モニタリング法の確立と活用

取得学位：博士(薬学)，学位授与番号：博甲第554号，学位授与年月日：平成15年3月25日,学位授与年：200

The Relationship Between Dialysis Patients' Quality of Life and Caregivers' Quality of Life

Patients on dialysis require caregiving and assistance in their daily lives from family members and/or others for hospital visitation and supervised administration. This places a considerable burden on caregivers, which can in turn influence caregivers' quality of life (QOL). We recruited dialysis patients and their caregivers to elucidate how the QOL of patients relates to that of their caregivers'. Patients completed the EuroQol 5-Dimension scale (EQ-5D) and Kidney Disease Quality of Life-Short Form. Caregivers completed the EQ-5D and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We calculated utility index values for the EQ-5D, and physical, mental (MCS), and role-social component summary scores for the SF-36. Compared to national norms, the caregivers of dialysis patients tended to have poor physical health-related QOL but normal mental health-related QOL, as also found with patients. The multivariate analysis revealed that ≥ median dialysis period and ≥ average burden of kidney disease were significantly related to caregiver MCS score (odds ratios; 6.79 and 9.89, respectively). Caregivers tended to have lower physical health-related QOL if their patients had high social QOL, and lower mental health-related QOL during the early stage of the patient's dialysis treatment, and when patients experienced low disease-targeted QOL

Factors Influencing Medicine Use Behavior in Adolescents in Japan Using a Bayesian Network Analysis

Background: Medicine education in Japan was introduced to junior high schools in 2012. However, the effectiveness of existing education programs is limited. In order to develop more effective programs for high school students, the present study investigated the variables that directly influence medicine use behavior and the magnitude of their influence, using a Bayesian network analysis.Methods: A national cross-sectional survey was conducted in 2017. Eighty-three public high schools across Japan were randomly selected, and questionnaires were administered to 15–16 years old 10th grade students. The number of valid responses was 17,437 (effective response rate was 98.46%). Responses were analyzed to measure students’ behavior toward, attitudes regarding, and knowledge of medicines, and awareness of their prior medicine education.Results: Students’ “attitude score” and “awareness of a class” directly influenced their “behavior score.” The “score on attitude,” which had a large influence on “score on behavior,” was directly influenced by “score on knowledge of proper use” and “awareness of class.”Conclusion: The present study argues that acquiring knowledge of appropriate medicine use leads to the acquisition of favorable attitudes, which may result in behavioral change. Therefore, for medicine education, it is expected that incorporating content related to knowledge acquisition for changing attitudes will be important for promoting behavioral change

Effectiveness of distributing pocket cards in improving the behavior, attitude, and knowledge regarding proper medication use among junior high school students in Japan

ObjectiveThis study aimed to explore the effectiveness of distributing pocket cards with summaries of key information on appropriate medication usage after the implementation of a structured school-based medication education program for junior high school students in Japan.MethodsA total of 227 3rd-grade high school students participated in the intervention. Students who received the program without the provision of pocket cards in 2022 were included in the comparison group, and students who took the program with the provision of pocket cards in 2023 were included in the intervention group. After propensity score matching, the final sample of N = 116 comprised n = 58 comparison group participants and n = 58 intervention group participants. Questionnaires were administered at baseline, end-of-class, and 3-month follow-up to assess the changes in behavior, attitude, and knowledge scores.ResultsThe matched intervention group showed significantly lower scores at the 3-month follow-up than the matched comparison group. The results of the multiple linear regression analysis showed that for both groups, only the attitude scores were significantly correlated with the behavior scores. In addition, regardless of the baseline scores, the matched intervention group demonstrated smaller or negative changes in scores at the 3-month follow-up.ConclusionOverall, the results of this study did not support the effectiveness of distributing pocket cards after in-class intervention. However, the usefulness of medication education intervention was confirmed. These results emphasize the need to explore other supplemental teaching tools to further enhance the impact of structured medication education programs

造血器腫瘍患者への化学療法支援に対する臨床薬学的研究

造血器腫瘍患者への化学療法は、強力で副作用の出現率も高い。副作用コントロールの善し悪しが治療の継続性、相対的治療強度（relative dose intensity： RDI）あるいはquality of life の低下に繋がる。まず筆者らは、非ホジキンリンパ腫患者に対する通常量化学療法後のステロイド離脱症状頻度とステロイド漸減療法による症状軽減効果の検討を行った。その結果、ステロイド漸減療法は安全で有効率も高く症状の改善が期待できた。特に高齢者の場合は、ステロイド離脱症状が強ければ積極的に早い段階から行う必要があると考えられた。次に、RDI に関与する重篤な感染症の1 つとして、非ホジキンリンパ腫患者における帯状疱疹の出現の解析を行った。帯状疱疹発症に関する有意な危険因子として、自己末梢血幹細胞移植後、再発患者、総治療回数10 回以上、使用レジメン2 種類以上が見出された。帯状疱疹発症の危険性がある患者へは、少量の抗ウイルス薬の予防投与を考慮すべきであり、他の感染同様に注意深く経過観察を行う必要があることを明らかにした。さらに、造血器腫瘍領域において真菌感染の第一選択薬に推奨され汎用されているLiposomal-Amphotericin B 投与による低カリウム血症と適正なカリウム補正に関する検討を行った。Grade3 以上の低カリウム血症は53.8%出現し、血清カリウム値が2.83 mEq/L を下回る前にカリウム補正を開始することが必要であり、血清カリウム値が低下しすぎない早期から補正を行うことが電解質異常の重篤化を予防するために重要であることを明らかにした。The chemotherapy treatment of hematological patients is associated with an increased risk of adverse events because of theintensity of the treatment. Adverse event management leads to continuous treatments, a relative dose intensity, and quality of life.Therefore, we evaluated the prevalence of steroid withdrawal syndrome (SWS) to assess the relevance of steroid tapering innon-Hodgkin lymphoma (NHL) patients who received general NHL chemotherapy. We conclude that steroid tapering is a safe andeffective treatment method. If the patient has serious symptoms of SWS, steroid tapering should be introduced aggressively and early,especially in elderly patients. We then examined the frequency of herpes zoster as a fatal infection in NHL patients. Significant riskfactors for the development of herpes zoster were post-autologous peripheral blood stem cell transplantation, relapse, 10 or more totaltreatments, and the use of two or more regimens. We recommend that it is necessary to consider the prophylactic use of low-doseanti-viral drugs in patients who have a higher risk of herpes zoster. We also recommend further observation of other opportunisticinfections associated with chemotherapy usage. In addition, we examined the appropriate potassium supplementation conditions totreat hypokalemia induced by liposomal-amphotericin B (L-AMB), which is recommended as a first-line anti-fungal drug forhematological patients. Hypokalemia greater than grade 3 was exhibited by 53.8% patients. It is necessary to begin potassiumsupplementation prior to the reduction of serum potassium levels to <2.83 mEq/l. Potassium supplementation at an early stage ofL-AMB treatment is important to prevent severe electrolyte abnormalities

がん薬物療法における薬学的介入の指標構築に関する研究

病院薬剤師は、医師と協働して、薬学的介入、すなわち、患者に最適な薬物療法を提供する必要がある。特に、がん化学療法においては有効で安全な治療を継続し、終末期ケアではquality of life (QOL)の維持・向上を目的とした処方設計が、臨床上の課題である。そこで、がん薬物療法時に、病院薬剤師による薬学的介入のための指標を構築することを目的に研究を行った。胃がん術後補助化学療法におけるtegafur・gimeracil・oteracil potassium（S-1）療法では、手術前からS-1 服薬開始時までのbody mass index 減少量は、治療が中止・減量となった患者（2.78±1.89）より継続できた患者（1.68±0.83）の方が小さいことを明らかにした。また、副作用によりS-1 の減量または中止に影響を及ぼす有意な因子として、血清アルブミン値<3.5g/dL、クレアチニンクリアランス値<80mL/min が見出された。在宅用高カロリー輸液の処方設計として、あらかじめ高カロリー輸液内にインスリンを添加したものを投薬せざるを得ない場合、溶液中の亜硫酸水素ナトリウム1g に対する糖質のグラム数（G/g）が364.6 以下の場合、インスリンの残存率は低下を示し、466.0 以上の場合には低下を示さないことを見出した。以上、本研究において得られた知見は、臨床に携わる薬剤師が、がん薬物療法時に薬学的介入を実践する際の極めて有用な指標となり、副作用の予防および治療効率の向上に貢献できた。Hospital pharmacists, in collaboration with doctors, must provide pharmaceutical interventions, namely,pharmacotherapies optimized to the patient. Continued, effective, and safe therapies in cancer chemotherapy and pharmacotherapydesigns that aim to maintain and improve quality of life in terminal care are particularly challenging in a clinical setting. Therefore,we aimed to establish indicators for pharmaceutical intervention during cancer pharmacotherapy for use by hospital pharmacists. Foradjuvant chemotherapy with tegafur/gimeracil/oteracil potassium (S-1) after surgery for stomach cancer, reductions in body massindex during the time before surgery to commencing the administration of S-1 were less in the patients who were able to continue theS-1 treatment (1.68 ± 0.83) than in the patients in whom therapy had to be ceased or reduced (2.78 ± 1.89). Additionally, significantfactors correlated with cessation or reduction of S-1 owing to adverse effects included serum albumin levels < 3.5 g/dL and creatinineclearance rates < 80 mL/min. For total parenteral nutrition for home use, when the addition of insulin to total parenteral nutritioncould not be avoided, the residual ratio of insulin was reduced if the number of grams of carbohydrates per gram of sodium bisulfite(G/g) was ≤364.6, but not if the number of grams was ≥466.0. Indicators of the terminal stage in patients, such as reduced food intakeand abnormalities in kidney or liver function, were used to establish a condition score. In those with scores of ≥6/11 points, steroidshad little effect on malaise. In conclusion, the findings of the present study are very useful indicators, for pharmacists, in a clinicalsetting. They may help to prevent adverse effects and to improve efficacy when implementing pharmaceutical interventions duringcancer pharmacotherapy

Effect of Dipeptidyl Peptidase-4 Inhibitors vs. Metformin on Major Cardiovascular Events Using Spontaneous Reporting System and Real-World Database Study

Background: Metformin had been recommended as the first-line treatment for type 2 diabetes since 2006 because of its low cost, high efficacy, and potential to reduce cardiovascular events, and thus death. However, dipeptidyl peptidase-4 (DPP-4) inhibitors are the most commonly prescribed first-line agents for patients with type 2 diabetes in Japan. Therefore, it is necessary to clarify the effect of DPP-4 inhibitors on preventing cardiovascular events, taking into consideration the actual prescription of antidiabetic drugs in Japan. Methods: This study examined the effect of DPP-4 inhibitors on preventing cardiovascular events. The Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system in Japan, and the Japanese Medical Data Center (JMDC) Claims Database, a Japanese health insurance claims and medical checkup database, were used for the analysis. Metformin was used as the DPP-4 inhibitor comparator. Major cardiovascular events were set as the primary endpoint. Results: In the analysis using the JADER database, a signal of major cardiovascular events was detected with DPP-4 inhibitors (IC: 0.22, 95% confidence interval: 0.03–0.40) but not with metformin. In the analysis using the JMDC Claims Database, the hazard ratio of major cardiovascular events for DPP-4 inhibitors versus metformin was 1.01 (95% CI: 0.84–1.20). Conclusions: A comprehensive analysis using two different databases in Japan, the JADER and the JMDC Claims Database, showed that DPP-4 inhibitors, which are widely used in Japan, have a non-inferior risk of cardiovascular events compared to metformin, which is used as the first-line drug in the United States and Europe

Improved Detection Criteria for Detecting Drug-Drug Interaction Signals Using the Proportional Reporting Ratio

There is a current demand for “safety signal” screening, not only for single drugs but also for drug-drug interactions. The detection of drug-drug interaction signals using the proportional reporting ratio (PRR) has been reported, such as through using the combination risk ratio (CRR). However, the CRR does not consider the overlap between the lower limit of the 95% confidence interval of the PRR of concomitant-use drugs and the upper limit of the 95% confidence interval of the PRR of single drugs. In this study, we proposed the concomitant signal score (CSS), with the improved detection criteria, to overcome the issues associated with the CRR. “Hypothetical” true data were generated through a combination of signals detected using three detection algorithms. The signal detection accuracy of the analytical model under investigation was verified using machine learning indicators. The CSS presented improved signal detection when the number of reports was ≥3, with respect to the following metrics: accuracy (CRR: 0.752 → CSS: 0.817), Youden’s index (CRR: 0.555 → CSS: 0.661), and F-measure (CRR: 0.780 → CSS: 0.820). The proposed model significantly improved the accuracy of signal detection for drug-drug interactions using the PRR