Journal of Pharmaceutical Health Care and Sciences最新文献

Background: Comprehensive medication regimens increase the risk of potential drug-drug interactions, adversely affecting health outcomes regardless of age. This risk is particularly pertinent in the context of medical vocational rehabilitation for middle-aged patients, who aim at facilitating rapid reintegration into employment. Identifying and addressing unfavourable drug regimens may substantially contribute to the effectiveness of interdisciplinary therapeutic interventions.

Methods: The retrospective cohort study was conducted among middle-aged soldiers diagnosed with post-traumatic stress disorder and at least one physical impairment and long-term medication intake. Patient records were analysed to investigate the nature of the medication such as the number of drugs and distribution according to the anatomical therapeutic code classification and drug-drug interactions in relation to bicycle ergometry performance.

Results: A substantial majority (73.2%) of all patients enrolled were prescribed an average of 3.0 (± 2.0) long-term medications per person. All patients received treatments containing ATC N drugs, which exert antidepressant properties. On average, each patient encountered the possible risk of 1.7 (± 1.3) drug interactions. Patients administered at least two ATC N drugs exhibited reduced maximum performance compared to controls. Conversely, patients receiving at least two drugs, wherein only one drug classified as ATC N, did not demonstrate significant performance differences from the control group. Notably, treatments incorporating selective monoamine reuptake inhibitors significantly reduced maximum performance relative to controls. The risk for potential drug-drug interactions, particularly those leading to QT interval prolongation, accounted for 47.5% of interactions involving ATC N drugs. Patients exclusively exposed to potential QT-prolonging interactions exhibited significantly reduced maximum performance compared to controls as well as patients who experienced different potential interactions.

Conclusion: Potential drug-drug interactions and disadvantageous drug combinations were prevalent among middle-aged adults with psychiatric disorders and may hinder a positive prognosis for physical fitness. The findings of this study underscore the importance of personalized medication management and continuous monitoring to mitigate negative impacts. Clinicians should diligently review patients' medication records and adjust therapies accordingly to prevent adverse drug reactions. Proactive strategies, such as regular medication reviews and drug-drug interaction screening tools, may be essential for optimizing therapeutic efficacy and maintaining physical performance.

Background: Horse antithymocyte globulin (hATG) is an important therapeutic option for aplastic anemia (AA). However, hATG carries the risk of fatal anaphylaxis, and skin tests are performed to identify high-risk patients. We report on the successful desensitization of two AA patients with positive skin tests to hATG.

Case presentation: Case 1: A 72-year-old man with a history of successful treatment with rabbit ATG was referred for pancytopenia. Neutrophil, reticulocyte, and platelet counts were 546 /µL, 32,000 /µL, and 19,000 /µL, despite the oral administration of eltrombopag and cyclosporine. Bone marrow biopsy showed hypocellularity, and he was diagnosed with relapsed severe AA. Case 2: A 69-year-old man was referred for anemia and thrombocytopenia, and diagnosed with non-severe AA. Neutrophil, reticulocyte, and platelet counts were 2,044 /µL, 23,000 /µL, and 37,000 /µL. Bone marrow biopsy revealed hypocellularity. Neither patient had a history of allergy, and the skin prick test (SPT) of hATG was negative, but the intradermal test (IDT) was positive. The result of the IDT in case 2 was reproducible. They received hATG desensitization under close monitoring of vital signs in our high-care unit. The protocol consisted of gradually increasing doses of hATG (four intradermal, two subcutaneous, and four intravenous (IV) push) and some premedications prior to administration of the full dose IV drip. They completed the course without developing any systemic allergic reactions.

Conclusions: Despite the risk of anaphylaxis, hATG desensitization can be beneficial in AA patients with a positive skin test, especially when no alternative is available or hATG is preferred.

Background: Vancomycin (VCM) induces nephrotoxicity in a dose-dependent manner, and patients with risk factors for nephrotoxicity have been reported to develop nephrotoxicity even within the effective concentration range. In the present study, we investigated measures to set an appropriate AUCss for each case by assessing the risk of developing nephrotoxicity using logistic regression curves, separating patients into a High-risk group with risk factors associated with nephrotoxicity when VCM is used and a Low-risk group without risk factors.

Methods: A multivariate logistic regression analysis was used to identify risk factors for nephrotoxicity. The AUCss threshold was selected by a CART analysis and ROC curves, and a logistic regression analysis was used to examine the relationship between AUCss and the probability of developing nephrotoxicity.

Results and discussion: The incidence of nephrotoxicity was 31.7% (33/104) in the High-risk group and 13.0% (14/108) in the Low-risk group, and was significantly higher in the former (p = 0.001). The AUCss threshold was set at 575 mg·h/L for the High-risk group and 650 mg·h/L for the Low-risk group. The probability of developing nephrotoxicity in the High-risk group (104 patients) was high: AUCss 400 mg·h/L (16.8%), 500 mg·h/L (23.3%), and 575 mg·h/L (29.3%). The target concentration range was newly set at 400 ≤ AUCss < 500, suggesting that the target AUCss needs to be considered for each patient based on the balance between therapeutic efficacy and the prevention of adverse effects. The probability of developing nephrotoxicity in the Low-risk group (108 patients) was AUCss 500 mg·h/L (4.7%), 575 mg·h/L (8.4%), and 650 mg·h/L (14.6%). Since the Low-risk group has a high safety profile, the target concentration range was newly set at 400 ≤ AUCss < 650, suggesting the safe administration of the drug up to AUCss 650 mg·h/L while aiming for AUCss 600 mg·h/L from the initial dose design.

Conclusion: In the present study, the risk of nephrotoxicity for each AUCss was quantitatively analyzed using logistic regression curves for the High- and Low-risk groups. This allowed for the proposal of strategic individual target concentrations based on the balance between risk and benefit.

Background: It has been reported that the protein binding rate of vancomycin (VCM) varies among individual patients. So, the authors investigated relevant factors that may affect free VCM concentration and target attainment of free area under the concentration-time curve (fAUC).

Methods: Thirty-nine patients were included. Multiple regression analysis was performed to determine the valuable factors in the free VCM concentration, and the target attainment of area under the concentration-time curve (AUC) 400-600 mg・h/L and fAUC200-300 mg・h/L was calculated.

Results: We found total protein was significant covariate for free VCM. Among 18 patients who were investigated for AUC and fAUC estimation, 9 patients (50.0%) and 12 patients (66.7%) reached AUC > 600 mg・h/L, and fAUC > 300 mg・h/L (p = 0.310), respectively.

Conclusions: Total protein is a significant predictor for free VCM estimation. And the fAUC-guided TDM for VCM TDM may contribute to more strict dosing than the AUC-guided TDM in hyper- or hypo-proteinemic population.

Trial registration: Retrospectively registered.

Background: Considering the global threat of antimicrobial resistance (AMR), Japan implemented a national action plan in 2016 that emphasized antibiotic education for healthcare professionals. However, pharmacy education in Japan lacks comprehensive antimicrobial stewardship (AMS) content, leading to insufficient antibiotic awareness and literacy among graduates. This study aimed to assess and improve antibiotic literacy and awareness among undergraduate pharmacy students at Showa University.

Methods: Students who were admitted in 2015 were given a 90-min lecture on AMS, covering acute upper respiratory infections, before their fifth-year clinical training in 2019. The lecture was delivered by a certified pharmacist in infection control. A paper-based, anonymous self-administered questionnaire survey on antibiotic knowledge and literacy was distributed to first- and fifth-year students in 2019 and fifth-year students in 2023. The questions in the survey were based on the Antibiotics Awareness Survey 2018.

Results: The survey results showed an 82-99% response rate among first- and fifth-year pharmacy students in 2019 and 2023. Although two-thirds of first-year pharmacy students lacked antibiotic knowledge, most fifth-year students had appropriate knowledge. Moreover, fifth-year students had a proper understanding of bacterial infections and antibiotic identification, which improved after clinical training and additional lectures. The percentage of students who would stop using antibiotics when they felt better dropped from 39% among first-year students to 21% among fifth-year students. Fifth-year students were more likely to dispose of leftover antibiotics and less likely to keep them than first-year students. Over 80% of students provided antibiotic counseling primarily for common cold treatments during clinical training.

Conclusions: The survey results highlighted gaps in antibiotic awareness among Japanese pharmacy students and demonstrated the positive impact of education. This study emphasizes the need for an antibiotic literacy curriculum, especially for viral respiratory infections, to support efforts in curbing AMR. Moreover, policymakers should develop policies for developing and securing faculty that are knowledgeable in clinical infectious diseases across Japanese pharmacy schools.

Background: In Japan, anticholinergic drugs were contraindicated for glaucoma, regardless of subtype. The contraindication in patients with open-angle glaucoma (OAG) led to excessive medication restrictions because anticholinergic drugs are associated with a low risk of acute glaucoma attacks in OAG. To eliminate this problem, the contraindications of anticholinergic drugs were reduced for types from all glaucoma to angle closure glaucoma (ACG) in 2019. This change requires differentiation of OAG from ACG for the proper use of drugs. The Japan Ophthalmologists Association created Glaucoma Information Cards to share glaucoma subtypes and restricted the medication list. However, only a few studies have investigated the efficacy of Glaucoma Information Cards. In this study, we evaluated the benefits of identifying glaucoma subtypes prior to admission by distributing Glaucoma Information Cards to patients through pharmacists.

Methods: Pharmacists distributed Glaucoma Information Cards to patients whose glaucoma subtype was unclear at the time of the preadmission pharmacist interview and asked them to have the treating ophthalmologist fill out the glaucoma subtype data. We collected patient data, hospitalized clinical department, status of realization of glaucoma subtypes, methods of realization of glaucoma subtypes, and usage of anticholinergic drugs from medical records.

Results: First, we investigated how hospital pharmacists identify the type of glaucoma. Pharmacists were able to determine the glaucoma type of most patients through medical records, patient interviews, and the Glaucoma Information Card. We analyzed the records of patients who were scheduled for ophthalmology visits prior to admission and had been given Glaucoma Information Cards. Eleven of the 13 patients brought the Glaucoma Information Card to the hospital, which was analyzed by an ophthalmologist. Two patients were administered anticholinergic drugs without restriction because of proven OAG according to the Glaucoma Information Card. One patient was administered cibenzoline for atrial fibrillation. Another patient received isosorbide dinitrate for coronary angiography. These cases indicate that the distribution of Glaucoma Information Cards can help avoid unnecessary medication restrictions in patients with OAG.

Conclusions: Our results suggest that the distribution of the Glaucoma Information Cards is useful for proper drug use in patients with glaucoma.

Background: Stroke is a leading cause of death, reducing disability-free life expectancy. After acute treatment, patients require rehabilitation to prevent recurrence. Continued use of medication is crucial for recurrence prevention and risk management, even after the transition from acute-care institutions to other medical institutions. Although "discharge summaries on medications" are shared between hospitals and community pharmacists, no reports have addressed medication continuity for patients with stroke transferred to other institutions after discharge. This study aimed to clarify medication continuity, particularly for medications adjusted during hospitalization that should be continued even after discharge, by investigating the medication use histories of patients with stroke transferred from acute care hospitals to outpatient hospitals.

Methods: We enrolled patients who were discharged from an acute ward between June 11, 2022, and March 31, 2023, after receiving inpatient care at the Japan Community Healthcare Organization, Hoshigaoka Medical Center for acute stroke, and transferred to other outpatient hospitals. This study was conducted between June 2022 and April 2023. We extracted and assessed prescription continuity and carefully examined clinically relevant discrepancies after comparing the discharge prescription with that at the first outpatient visit.

Results: Of the 42 patients enrolled, seven (16.7%) had one or more discrepancies involving 13 medications. Based on the medicinal efficacy classification, four patients treated with other blood and body fluids-related agents (antiplatelet drugs), three patients treated with agents for hyperlipidemia (statins), two patients with agents for peptic ulcers, two patients with vasodilators, one patient treated with antihypertensives, and one patient with other agents affecting digestive organs (antiemetic agents that acts on the central nervous system) had discrepancies. Furthermore, discrepancies in medication discontinuation or reduction recommended by a stroke specialist, which may increase the risk of stroke recurrence, were identified in five patients (seven drugs: four antiplatelet drugs and three statins). Of 13 discrepancies, community pharmacists inquired about 3 cases with physicians, none were approved.

Conclusion: The medication to prevent stroke recurrence might not be continued after transit to another outpatient after discharge. Reconsidering patient information sharing between hospital and community pharmacists and establishing a more strengthened sharing system is necessary to achieve seamless pharmacotherapy.

Background: The Anticholinergic Risk Scale and Total Anticholinergic Load were developed to assess the risks associated with anticholinergic drugs. Recently, the Japan Anticholinergic Risk Scale was introduced; however, the total anticholinergic load for adverse events has not been clarified, and the criteria for risk assessment in clinical practice have not been established. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency to determine the total anticholinergic load associated with reported adverse events related to anticholinergic syndrome.

Methods: Using JADER data from April 2004 to September 2023, we investigated the association between drugs included in the J-ARS and adverse events related to anticholinergic syndrome. In addition, we calculated the total anticholinergic load for each case involving a drug recorded in the JADER database and compared it with other adverse events associated with anticholinergic effects.

Results: Based on the JADER data, we observed an association between anticholinergic syndrome-related adverse events and the drugs listed in the J-ARS, confirming the feasibility of calculating the total anticholinergic drug burden for each case. In the group reporting anticholinergic syndrome-related adverse events, the mean ± standard deviation of the total anticholinergic load was 4.20 ± 3.09.

Conclusions: The mean total anticholinergic load of anticholinergic syndrome-related adverse events obtained from the JADER database in this study supports the development of a comprehensive risk assessment of anticholinergic drugs in clinical practice.

Background: Cataract surgeries are increasing annually, making appropriate medical management essential. The routine use of systemic antimicrobial agents for preventing surgical site infections lacks strong evidence and may increase the risk of drug-resistant bacteria and adverse events. This study examined the impact of discontinuing cefazolin (CEZ) administration during the perioperative period of cataract surgery on the incidence of postoperative adverse events and medical costs.

Methods: Inpatient cataract surgery patients were divided into two groups: the CEZ-use group (April 2021 to March 2022) and the non-CEZ-use group (April 2022 to March 2023). The primary endpoints were the incidence of adverse events and medical costs, while the secondary endpoint was the incidence of endophthalmitis.

Results: A total of 265 patients were in the CEZ group, and 316 were in the non-CEZ group. Six postoperative adverse events (2.3%, 95% confidence interval: 0.8-4.9) occurred in the CEZ group, with an estimated 230 patients (80-490 from the 95% confidence interval) expected to experience adverse events per 10,000 patients using CEZ. The non-CEZ group had no adverse events and reduced drug costs by approximately 46,000 yen. Insurance claim amounts were also reduced. No cases of early postoperative endophthalmitis were observed in either group.

Conclusions: Discontinuation of CEZ prophylaxis during the perioperative period of cataract surgery effectively reduced the risk of adverse events. Medical for the period after discontinuing CEZ did not increase.

Trial registration: Retrospectively registered.

Background: Pharmaceutical formularies play a crucial role in guiding medication use by balancing clinical effectiveness and cost efficiency. Although formulary implementation has been increasing in Japan, comprehensive evaluations of its impact on both clinical and economic outcomes are limited. This study aimed to assess the effect of introducing an antimicrobial formulary at Yokohama City University Hospital on antibiotic usage and treatment outcomes in intra-abdominal infections.

Methods: We conducted a segmented time-series analysis to evaluate changes in carbapenem usage, including doripenem, before and after formulary implementation in October 2018. Monthly antibiotic consumption was measured by antibiotic use density (AUD). The primary outcomes were changes in doripenem use and treatment efficacy for intra-abdominal infections. To assess treatment efficacy, we used non-inferiority analysis with propensity score matching based on age, sex, body mass index, cancer status, and baseline blood test results. The treatment outcomes were evaluated using predefined clinical indicators.

Results: Following the formulary intervention, doripenem use significantly decreased from 10.8 to 4.9%, meropenem use slightly increased, and imipenem/cilastatin usage remained stable. Overall, carbapenem use significantly decreased during the study period. Treatment effectiveness for intra-abdominal infections remained non-inferior, with a higher proportion of patients classified as having an "effective" response post-intervention (86.6% vs. 79.4% pre-intervention). The confidence interval confirmed the non-inferiority margin, indicating no clinically significant reduction in treatment effectiveness following the formulary introduction.

Conclusions: The introduction of an antibiotic formulary at Yokohama City University Hospital effectively reduced the use of doripenem without compromising the effectiveness of treatment of intra-abdominal infections. These findings suggest that formulary management can be a valuable strategy for optimizing antibiotic use while maintaining clinical outcomes and contributing to improved antimicrobial stewardship in healthcare settings. Further research is warranted to explore the broader implications of formulary implementation in Japanese healthcare practices.